ORCID Profile
0000-0003-0237-1473
Current Organisations
University of Melbourne at The Doherty Institute
,
Queensland University of Technology
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Veterinary Microbiology (excl. Virology) | Veterinary Epidemiology | Veterinary Sciences | Infectious Agents | Microbial Ecology | Genomics | Genetics | Veterinary Sciences not elsewhere classified | Biodiscovery |
ANZSRC Socio-Economic Objective (SEO)
Biofuel (Biomass) Energy | Ecosystem Adaptation to Climate Change | Pigs | Respiratory System and Diseases (incl. Asthma) | Livestock Product Traceability and Quality Assurance | Expanding Knowledge in the Biological Sciences | Food Safety | Infectious Diseases
Related Links
Publications
Vancomycin AUC/MIC Ratio and 30-Day Mortality in Patients with Staphylococcus aureus Bacteremia
Publisher: American Society for Microbiology
Date: 04-2013
DOI: 10.1128/AAC.01485-12
Abstract: A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a “real-world” context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively P 0.001). Obtaining the recommended vancomycin target AUC/MIC of ≥400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB ( P = 0.132 and P = 0.273, respectively). However, an alternative vancomycin AUC/MIC of , derived using classification and regression tree analysis, was associated with reduced mortality ( P = 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, ) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.
Prolonged Outbreak of Multidrug-Resistant Shigella sonnei Harboring bla CTX-M-27 in Victoria, Australia
Publisher: American Society for Microbiology
Date: 17-11-2020
DOI: 10.1128/AAC.01518-20
Abstract: In Australia, cases of shigellosis usually occur in returned travelers from regions of shigellosis endemicity or in men who have sex with men. Resistance to multiple antibiotics has significantly increased in Shigella sonnei isolates and represents a significant public health concern. We investigate an outbreak of multidrug-resistant S. sonnei in Victoria, Australia. We undertook whole-genome sequencing of 54 extended-spectrum-beta-lactamase (ESBL)-producing S. sonnei isolates received at the Microbiological Diagnostic Unit Public Health Laboratory between January 2019 and March 2020.
A large outbreak of Campylobacter jejuni infection in a university college caused by chicken liver pâté, Australia, 2013
Publisher: Cambridge University Press (CUP)
Date: 16-06-2016
DOI: 10.1017/S0950268816001187
Abstract: In October 2013, public health authorities were notified of a suspected outbreak of gastroenteritis in students and guests following a catered function at a university residential college. A retrospective cohort study was undertaken to examine whether foods served at the function caused illness. A total of 56 cases of gastroenteritis, including seven laboratory-confirmed cases of C ylobacter jejuni infection, were identified in 235 eligible respondents. Univariate analysis showed a significant association with a chicken liver pâté entrée [relative risk (RR) 3·64, 95% confidence interval (CI) 2·03–6·52, P 0·001], which retained significance after adjustment for confounding via multivariable analysis (adjusted RR 2·80, 95% CI 1·26–6·19, P = 0·01). C. jejuni and C. coli were also isolated in chicken liver pâté recovered from the college's kitchen. Subsequent whole genome multilocus sequence typing (wgMLST) of clinical and food-derived C. jejuni isolates showed three genetically distinct sequence types (STs) comprising ST528, ST535 (both clinically derived) and ST991 (food derived). The study demonstrates the value of utilizing complementary sources of evidence, including genomic data, to support public health investigations. The use of wgMLST highlights the potential for significant C. jejuni ersity in epidemiologically related human and food isolates recovered during outbreaks linked to poultry liver.
Rapidly progressive renal failure associated with successful pharmacotherapy for obesity
Publisher: Oxford University Press (OUP)
Date: 29-03-2007
DOI: 10.1093/NDT/GFM203
Niche-specific genome degradation and convergent evolution shaping Staphylococcus aureus adaptation during severe infections.
Publisher: eLife Sciences Publications, Ltd
Date: 14-06-2022
DOI: 10.7554/ELIFE.77195
Abstract: During severe infections, Staphylococcus aureus moves from its colonising sites to blood and tissues and is exposed to new selective pressures, thus, potentially driving adaptive evolution. Previous studies have shown the key role of the agr locus in S. aureus pathoadaptation however, a more comprehensive characterisation of genetic signatures of bacterial adaptation may enable prediction of clinical outcomes and reveal new targets for treatment and prevention of these infections. Here, we measured adaptation using within-host evolution analysis of 2590 S . aureus genomes from 396 independent episodes of infection. By capturing a comprehensive repertoire of single nucleotide and structural genome variations, we found evidence of a distinctive evolutionary pattern within the infecting populations compared to colonising bacteria. These invasive strains had up to 20-fold enrichments for genome degradation signatures and displayed significantly convergent mutations in a distinctive set of genes, linked to antibiotic response and pathogenesis. In addition to agr -mediated adaptation, we identified non-canonical, genome-wide significant loci including sucA-sucB and stp1 . The prevalence of adaptive changes increased with infection extent, emphasising the clinical significance of these signatures. These findings provide a high-resolution picture of the molecular changes when S. aureus transitions from colonisation to severe infection and may inform correlation of infection outcomes with adaptation signatures.
Recent trends in invasive group A Streptococcus disease in Victoria
Publisher: Australian Government Department of Health
Date: 15-03-2019
Abstract: Background Invasive Group A Streptococcus (iGAS) disease can cause permanent disability and death. The incidence of iGAS has increased in many developed countries since the 1980s. iGAS disease is not nationally notifiable in Australia or at the state level in Victoria. The Victorian Hospital Pathogen Surveillance Scheme (VHPSS) is a voluntary laboratory-based surveillance system established in 1988. We assessed the trends and molecular epidemiology of iGAS disease in Victoria from 2007-2017. Methods A case of iGAS was defined as an in idual for whom Group A Streptococcus (GAS) was isolated from a normally sterile body site. Data on all iGAS cases, as reported to the VHPSS, between 1 January 2007 and 31 December 2017 were examined. Results A total of 1,311 iGAS cases had associated isolates, and M Protein Gene (emm) typing was performed for 91.6%. The mean annual incidence was 2.1 (95% CI: 1.8-2.5) per 100,000 population per year, increasing 2.7-fold over the study period. In total, 140 different iGAS emm-types were observed, with the ten most prevalent types comprising 63.1% of the s le. Conclusions Despite limitations in this surveillance data, we observed increasing rates of iGAS disease in Victoria. iGAS incidence exceeded the mean annual incidence for invasive meningococcal disease, calculated using Victorian data from the National Notifiable Diseases Surveillance System (2.1 vs. 0.6 cases per 100,000 population per year, respectively). Mandatory case notification could enhance disease control and prevention. Further, the ersity in emm-types emphasises the importance of effective secondary chemoprophylaxis in prevention, alongside GAS vaccine development.
High performanceLegionella pneumophilasource attribution using genomics-based machine learning classification
Publisher: Cold Spring Harbor Laboratory
Date: 22-03-2023
DOI: 10.1101/2023.03.19.532693
Abstract: Fundamental to effective Legionnaires’ disease outbreak control is the ability to rapidly identify the environmental source(s) of the causative agent, Legionella pneumophila . Genomics has revolutionised pathogen surveillance but L. pneumophila has a complex ecology and population structure that can limit source inference based on standard core genome phylogenetics. Here we present a powerful machine learning approach that assigns the geographical source of Legionnaires’ disease outbreaks more accurately than current core genome comparisons. Models were developed upon 534 L. pneumophila genome sequences, including 149 genomes linked to 20 previously reported Legionnaires’ disease outbreaks through detailed case investigations. Our classification models were developed in a cross-validation framework using only environmental L. pneumophila genomes. Assignments of clinical isolate geographic origins demonstrated high predictive sensitivity and specificity of the models, with no false positives or false negatives for 13 out of 20 outbreak groups, despite the presence of within-outbreak polyclonal population structure. Analysis of the same 534-genome panel with a conventional phylogenomic tree and a core genome multi-locus sequence type allelic distance-based classification approach revealed that our machine learning method had the highest overall classification performance – agreement with epidemiological information. Our multivariate statistical learning approach maximises use of genomic variation data and is thus well-suited for supporting Legionnaires’ disease outbreak investigations.
Trends and Risk Factors for Antimicrobial-Resistant Neisseria gonorrhoeae , Melbourne, Australia, 2007 to 2018
Publisher: American Society for Microbiology
Date: 10-2019
DOI: 10.1128/AAC.01221-19
Abstract: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health problem. Traditionally, AMR surveillance programs for N. gonorrhoeae have focused mainly on laboratory data to describe the prevalence and trends of resistance. However, integrating in idual-level risk factors (e.g., sexual orientation or international travel) with laboratory data provides important insights into factors promoting the spread of resistant N. gonorrhoeae .
Surveillance for SARS‐CoV‐2 variants of concern in the Australian context
Publisher: AMPCo
Date: 31-05-2021
DOI: 10.5694/MJA2.51105
Investigating locally relevant risk factors for Campylobacter infection in Australia: Protocol for a case-control study and genomic analysis
Publisher: BMJ
Date: 12-2018
DOI: 10.1136/BMJOPEN-2018-026630
Abstract: The C ySource project aims to identify risk factors for human C ylobacter infection in Australia. We will investigate locally relevant risk factors and those significant in international studies in a case–control study. Case isolates and contemporaneous isolates from food and animal sources will be sequenced to conduct source attribution modelling, and findings will be combined with the case–control study in a source-assigned analysis. The case–control study will include 1200 participants (600 cases and 600 controls) across three regions in Australia. Cases will be recruited from c ylobacteriosis notifications to health departments. Only those with a pure and viable C ylobacter isolate will be eligible for selection to allow for whole genome sequencing of isolates. Controls will be recruited from notified cases of influenza, frequency matched by sex, age group and geographical area of residence. All participants will be interviewed by trained telephone interviewers using a piloted questionnaire. We will collect C ylobacter isolates from retail meats and companion animals (specifically dogs), and all food, animal and human isolates will undergo whole genome sequencing. We will use sequence data to estimate the proportion of human infections that can be attributed to animal and food reservoirs (source attribution modelling), and to identify spatial clusters and temporal trends. Source-assigned analysis of the case–control study data will also be conducted where cases are grouped according to attributed sources. Human and animal ethics have been approved. Genomic data will be published in online archives accompanied by basic metadata. We anticipate several publications to come from this study.
The two-component system WalKR provides an essential link between cell wall homeostasis and DNA replication in Staphylococcus aureus
Publisher: American Society for Microbiology
Date: 16-10-2023
Reporting practices for genomic epidemiology of tuberculosis: a systematic review of the literature using STROME-ID guidelines as a benchmark
Publisher: Elsevier BV
Date: 03-2021
Not Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA)! A Clinician's Guide to Community MRSA - Its Evolving Antimicrobial Resistance and Implications for Therapy
Publisher: Oxford University Press (OUP)
Date: 2011
DOI: 10.1093/CID/CIQ067
Abstract: There is significant ersity in methicillin-resistant Staphylococcus aureus (MRSA) clones arising in the community worldwide, with considerable geographical differences in typical antimicrobial resistance profiles. Many community clones of MRSA have a non-multidrug resistant antimicrobial profile, providing increased options for empirical and directed therapy of infections caused by these strains. However, the recent description of increasing non-β lactam resistance in community clones of MRSA, especially USA300, provides a timely warning for clinicians making decisions about therapy for patients potentially infected with these strains. Continued monitoring of global epidemiology and emerging drug resistance data is critical for the effective management of these infections.
Mining the Methylome Reveals Extensive Diversity in Staphylococcus epidermidis Restriction Modification
Publisher: American Society for Microbiology
Date: 24-12-2019
Abstract: Staphylococcus epidermidis is a major cause of hospital-acquired infections, especially those related to implanted medical devices. Understanding how S. epidermidis causes disease and devising ways to combat these infections have been hindered by an inability to genetically manipulate clinically significant hospital-adapted strains. Here, we provide the first comprehensive analyses of the barriers to the uptake of foreign DNA in S. epidermidis and demonstrate that these are distinct from those described for S. aureus . Using these insights, we demonstrate an efficient approach for the genetic manipulation of S. epidermidis to enable the study of clinical isolates for the first time.
Author response: Niche-specific genome degradation and convergent evolution shaping Staphylococcus aureus adaptation during severe infections
Publisher: eLife Sciences Publications, Ltd
Date: 17-05-2022
Glycemic Response to a Renal‐Specific Oral Nutritional Supplement in Patients With Diabetes Undergoing Hemodialysis: A Randomized Crossover Trial
Publisher: Wiley
Date: 18-08-2020
DOI: 10.1002/JPEN.1970
The risk of resistance: what are the major antimicrobial resistance threats facing Australia?
Publisher: Wiley
Date: 23-06-2019
DOI: 10.5694/MJA2.50249
The rise of antimicrobial resistance: a clear and present danger
Publisher: Informa UK Limited
Date: 06-2011
DOI: 10.1586/ERI.11.49
Abstract: The Australian Society for Antimicrobials aims to facilitate the acquisition and dissemination of knowledge in the field of antimicrobials. Members and delegates come from a erse range of professions including physicians, microbiologists, scientists, pharmacists, veterinarians and industry representatives from pharmaceutical and biomedical companies. Membership is primarily based in Australia and New Zealand, but extends to Asia, North America, Europe and the UK. A total of 330 participants attended the 2011 Annual Scientific Meeting with plenary speakers from the USA, Spain and Australia. This meeting report focuses on two key areas of antimicrobial resistance: community-associated methicillin-resistant Staphylococcus aureus and resistance in Gram-negative organisms.
Enterococcal bacteraemia: Factors influencing mortality, length of stay and costs of hospitalization
Publisher: Elsevier BV
Date: 04-2013
Should Asymptomatic Men Who Have Sex With Men Be Screened for Oropharyngeal Chlamydia? Clinical Outcomes From a Cross-Sectional Study
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2018
Assessment of the BD GeneOhm MRSA ACP assay using combined swabs for the detection of methicillin resistant Staphylococcus aureus (MRSA) colonisation
Publisher: Elsevier BV
Date: 10-2013
Incorporating Whole-Genome Sequencing into Public Health Surveillance: Lessons from Prospective Sequencing of Salmonella Typhimurium in Australia
Publisher: Mary Ann Liebert Inc
Date: 03-2018
Abstract: In Australia, the incidence of Salmonella Typhimurium has increased dramatically over the past decade. Whole-genome sequencing (WGS) is transforming public health microbiology, but poses challenges for surveillance. To compare WGS-based approaches with conventional typing for Salmonella surveillance, we performed concurrent WGS and multilocus variable-number tandem-repeat analysis (MLVA) of Salmonella Typhimurium isolates from the Australian Capital Territory (ACT) for a period of 5 months. We exchanged data via a central shared virtual machine and performed comparative genomic analyses. Epidemiological evidence was integrated with WGS-derived data to identify related isolates and sources of infection, and we compared WGS data for surveillance with findings from MLVA typing. We found that WGS data combined with epidemiological data linked an additional 9% of isolates to at least one other isolate in the study in contrast to MLVA and epidemiological data, and 19% more isolates than epidemiological data alone. Analysis of risk factors showed that in one WGS-defined cluster, human cases had higher odds of purchasing a single egg brand. While WGS was more sensitive and specific than conventional typing methods, we identified barriers to uptake of genomic surveillance around complexity of reporting of WGS results, timeliness, acceptability, and stability. In conclusion, WGS offers higher resolution of Salmonella Typhimurium laboratory surveillance than existing methods and can provide further evidence on sources of infection in case and outbreak investigations for public health action. However, there are several challenges that need to be addressed for effective implementation of genomic surveillance in Australia.
Seven Salmonella Typhimurium Outbreaks in Australia Linked by Trace-Back and Whole Genome Sequencing
Publisher: Mary Ann Liebert Inc
Date: 05-2018
Abstract: Salmonella Typhimurium is a common cause of foodborne illness in Australia. We report on seven outbreaks of Salmonella Typhimurium multilocus variable-number tandem-repeat analysis (MLVA) 03-26-13-08-523 (European convention 2-24-12-7-0212) in three Australian states and territories investigated between November 2015 and March 2016. We identified a common egg grading facility in five of the outbreaks. While no Salmonella Typhimurium was detected at the grading facility and eggs could not be traced back to a particular farm, whole genome sequencing (WGS) of isolates from cases from all seven outbreaks indicated a common source. WGS was able to provide higher discriminatory power than MLVA and will likely link more Salmonella Typhimurium cases between states and territories in the future. National harmonization of Salmonella surveillance is important for effective implementation of WGS for Salmonella outbreak investigations.
Population genomics provides insights into the evolution and adaptation to humans of the waterborne pathogen Mycobacterium kansasii
Publisher: Springer Science and Business Media LLC
Date: 03-05-2021
DOI: 10.1038/S41467-021-22760-6
Abstract: Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going ersification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii ’s success and its ongoing adaptation to the human host.
Evaluation of microalgae and cyanobacteria as potential sources of antimicrobial compounds
Publisher: Elsevier BV
Date: 12-2020
Use and safety of enteral nutrition protocols in acute care: A scoping review of literature and retrospective audit of practice
Publisher: Wiley
Date: 07-06-2023
Abstract: Standardised enteral nutrition protocols are recommended in critical care, however their use and safety are not well described in other inpatient populations. This mixed methods study reports on the use and safety of enteral nutrition protocols for non‐critically ill adults. A scoping review of published literature was conducted. In addition a retrospective audit of practice at an Australian tertiary teaching hospital with an existing hospital‐wide standardised enteral nutrition protocol was performed. Data on use, safety and adequacy of enteral nutrition prescription were collected from medical records for patients receiving enteral nutrition on acute wards (January–March 2020). Screening of 9298 records yielded six primary research articles. Studies were generally low quality. Published literature suggested that protocols may reduce time to enteral nutrition initiation and goal rate, and improve adequacy of nutrition provision. No adverse outcomes were reported. From the local audit of practice (105 admissions, 98 patients), enteral nutrition commencement was timely (median 0 (IQR 0–1) days from request goal rate: median 1 (IQR 0–2) days from commencement and adequate (nil underfeeding), without prior dietitian review in 82% of cases. Enteral nutrition was commenced per protocol in 61% of instances. No adverse events, including refeeding syndrome, were observed. Most inpatients requiring enteral nutrition can be safely and adequately managed on enteral nutrition protocols. Evaluation of protocols outside of the critical care setting remains a gap in the literature. Standardised enteral nutrition protocols may improve delivery of nutrition to patients, whilst allowing dietitians to focus on those with specialised nutrition support needs.
The ΦBT1 large serine recombinase catalyzes DNA integration at pseudo-attB sites in the genus Nocardia
Publisher: PeerJ
Date: 04-05-2018
DOI: 10.7717/PEERJ.4784
Abstract: Plasmid vectors based on bacteriophage integrases are important tools in molecular microbiology for the introduction of foreign DNA, especially into bacterial species where other systems for genetic manipulation are limited. Site specific integrases catalyze recombination between phage and bacterial attachment sites ( attP and attB , respectively) and the best studied integrases in the actinomycetes are the serine integrases from the Streptomyces bacteriophages ΦC31 and ΦBT1. As this reaction is unidirectional and highly stable, vectors containing phage integrase systems have been used in a number of genetic engineering applications. Plasmids bearing the ΦBT1 integrase have been used to introduce DNA into Streptomyces and Amycolatopsis strains however, they have not been widely studied in other actinobacterial genera. Here, we show that vectors based on ΦBT1 integrase can stably integrate into the chromosomes of a range of Nocardia species, and that this integration occurs despite the absence of canonical attB sites in these genomes. Furthermore, we show that a ΦBT1 integrase-based vector can insert at multiple pseudo- attB sites within a single strain and we determine the sequence of a pseudo- attB motif. These data suggest that ΦBT1 integrase-based vectors can be used to readily and semi-randomly introduce foreign DNA into the genomes of a range of Nocardia species. However, the precise site of insertion will likely require empirical determination in each species to avoid unexpected off-target effects.
Genomic epidemiology offers high resolution estimates of serial intervals for COVID-19
Publisher: Springer Science and Business Media LLC
Date: 10-08-2023
DOI: 10.1038/S41467-023-40544-Y
Abstract: Serial intervals – the time between symptom onset in infector and infectee – are a fundamental quantity in infectious disease control. However, their estimation requires knowledge of in iduals’ exposures, typically obtained through resource-intensive contact tracing efforts. We introduce an alternate framework using virus sequences to inform who infected whom and thereby estimate serial intervals. We apply our technique to SARS-CoV-2 sequences from case clusters in the first two COVID-19 waves in Victoria, Australia. We find that our approach offers high resolution, cluster-specific serial interval estimates that are comparable with those obtained from contact data, despite requiring no knowledge of who infected whom and relying on incompletely-s led data. Compared to a published serial interval, cluster-specific serial intervals can vary estimates of the effective reproduction number by a factor of 2–3. We find that serial interval estimates in settings such as schools and meat processing acking plants are shorter than those in healthcare facilities.
Genomic analysis of multi-resistant Staphylococcus capitis associated with neonatal sepsis
Publisher: American Society for Microbiology
Date: 11-2018
DOI: 10.1128/AAC.00898-18
Abstract: Coagulase-negative staphylococci (CoNS), such as Staphylococcus capitis , are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently, a distinct clone of S. capitis (designated S. capitis NRCS-A) has emerged as an important pathogen in NICUs internationally.
Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns
Publisher: American Society for Microbiology
Date: 07-2017
DOI: 10.1128/CMR.00112-16
Abstract: Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future.
Obesity and iron deficiency in chronic kidney disease: the putative role of hepcidin
Publisher: Oxford University Press (OUP)
Date: 15-12-2011
DOI: 10.1093/NDT/GFR686
Comparison of the bacterial isolates and antibiotic resistance patterns of elderly nursing home and general community patients
Publisher: Wiley
Date: 07-2012
DOI: 10.1111/J.1445-5994.2011.02436.X
Abstract: Nursing home-acquired infections may differ from general community-acquired infections in bacteriology and antibiotic resistance. However, there are currently limited data on this topic in the Australian setting. To compare bacterial isolates and antibiotic resistance patterns, from pathology specimens of nursing home and community patients, and to comment on the suitability of empiric antibiotic guidelines for nursing home-acquired infection. This was a retrospective cohort study of patients, aged ≥ 65 years, who resided in either nursing homes or the general community. Patients with a hospital admission in the previous 28 days were excluded. Positive specimen cultures, collected between July 2003 and June 2008 in the Emergency Department and Outpatient Clinics of the Austin Hospital (Melbourne), were examined. The main outcome measures were the bacterial isolates, and their antibiotic resistance patterns, of patients from nursing homes and the general community. Specimens of blood (638), sputum (425), urine (4044) and wound cultures (785) were examined. The bacteriology of blood culture isolates did not differ between the two groups (P= 0.3). However, the bacteriology of sputum, urine and wound cultures differed significantly between the groups (P= 0.025, P < 0.001, P= 0.004 respectively). There were also higher proportions of antibiotic resistance among some bacteria in nursing home patients, especially methicillin resistance among Staphylococcus aureus isolates across all specimen types, and resistance to several empiric antibiotics among Enterobacteriaceae isolates in urine cultures. Empiric antibiotic guidelines appear adequate to treat nursing home-acquired septicaemia and pneumonia. However, guidelines for urinary tract infections and wound infections may need to be refined.
Mycobacterium chimaera Spread from Heating and Cooling Units in Heart Surgery
Publisher: Massachusetts Medical Society
Date: 09-02-2017
DOI: 10.1056/NEJMC1612023
Genomics of vancomycin-resistant Enterococcus faecium
Publisher: Microbiology Society
Date: 07-2019
Abstract: Vancomycin-resistant Enterococcus faecium (VREfm) is a globally significant public health threat and was listed on the World Health Organization’s 2017 list of high-priority pathogens for which new treatments are urgently needed. Treatment options for invasive VREfm infections are very limited, and outcomes are often poor. Whole-genome sequencing is providing important new insights into VREfm evolution, drug resistance and hospital adaptation, and is increasingly being used to track VREfm transmission within hospitals to detect outbreaks and inform infection control practices. This mini-review provides an overview of recent data on the use of genomics to understand and respond to the global problem of VREfm.
Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus
Publisher: Springer Science and Business Media LLC
Date: 11-07-2019
DOI: 10.1038/S41467-019-10932-4
Abstract: WalKR (YycFG) is the only essential two-component regulator in the human pathogen Staphylococcus aureus . WalKR regulates peptidoglycan synthesis, but this function alone does not explain its essentiality. Here, to further understand WalKR function, we investigate a suppressor mutant that arose when WalKR activity was impaired a histidine to tyrosine substitution (H271Y) in the cytoplasmic Per-Arnt-Sim (PAS CYT ) domain of the histidine kinase WalK. Introducing the WalK H271Y mutation into wild-type S. aureus activates the WalKR regulon. Structural analyses of the WalK PAS CYT domain reveal a metal-binding site, in which a zinc ion (Zn 2+ ) is tetrahedrally-coordinated by four amino acids including H271. The WalK H271Y mutation abrogates metal binding, increasing WalK kinase activity and WalR phosphorylation. Thus, Zn 2+ -binding negatively regulates WalKR. Promoter-reporter experiments using S. aureus confirm Zn 2+ sensing by this system. Identification of a metal ligand recognized by the WalKR system broadens our understanding of this critical S. aureus regulon.
Community-onsetStaphylococcus aureusinfections presenting to general practices in South-eastern Australia
Publisher: Cambridge University Press (CUP)
Date: 18-07-2013
DOI: 10.1017/S0950268813001581
Abstract: Community-acquired Staphylococcus aureus infections are a public health concern, yet little is known about infections that do not present to hospital. We identified community-onset S. aureus infections via specimens submitted to a community-based pathology service. Referring doctors confirmed eligibility and described infection site, severity and treatment. Isolates were characterized on antibiotic resistance, PFGE, MLST/SCC mec , and Panton–Valentine leukocidin (PVL), representing 106 community-onset infections 34 non-multiresistant methicillin-resistant S. aureus (nmMRSA) (resistant to non- β -lactam antibiotics), 15 multiply antibiotic-resistant MRSA (mMRSA) and 57 methicillin-sensitive S. aureus (MSSA). Most (93%) were skin and soft tissue infections. PVL genes were carried by 42% of nmMRSA isolates [95% confidence interval (CI) 26–61] and 15% of MSSA (95% CI 8–28). PVL was associated with infections of the trunk, head or neck (56·4% vs . 24·3%, P = 0·005) in younger patients (23 vs . 52 years, P 0·001), and with boils or abscesses (OR 8·67, 95% CI 2·9–26·2), suggesting underlying differences in exposure and/or pathogenesis.
Evolutionary origins of the emergent ST796 clone of vancomycin resistant Enterococcus faecium
Publisher: PeerJ
Date: 24-01-2017
DOI: 10.7717/PEERJ.2916
Abstract: From early 2012, a novel clone of vancomycin resistant Enterococcus faecium (assigned the multi locus sequence type ST796) was simultaneously isolated from geographically separate hospitals in south eastern Australia and New Zealand. Here we describe the complete genome sequence of Ef_aus0233, a representative ST796 E. faecium isolate. We used PacBio single molecule real-time sequencing to establish a high quality, fully assembled genome comprising a circular chromosome of 2,888,087 bp and five plasmids. Comparison of Ef_aus0233 to other E. faecium genomes shows Ef_aus0233 is a member of the epidemic hospital-adapted lineage and has evolved from an ST555-like ancestral progenitor by the accumulation or modification of five mosaic plasmids and five putative prophage, acquisition of two cryptic genomic islands, accrued chromosomal single nucleotide polymorphisms and a 80 kb region of recombination, also gaining Tn 1549 and Tn 916 , transposons conferring resistance to vancomycin and tetracycline respectively. The genomic dissection of this new clone presented here underscores the propensity of the hospital E. faecium lineage to change, presumably in response to the specific conditions of hospital and healthcare environments.
Ceftazidime/avibactam susceptibility by three different susceptibility testing methods in carbapenemase-producing Gram-negative bacteria from Australia
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.IJANTIMICAG.2018.02.017
Abstract: Avibactam (AVI) is a novel β-lactamase inhibitor active against class A, class C and some class D β-lactamases. In combination with ceftazidime, AVI may be useful for the treatment of infections due to Gram-negative bacteria producing carbapenemases from these classes however, susceptibility data for some of the less common carbapenemases are limited. To assess the in vitro activity of ceftazidime/avibactam (CZA), a panel of 50 erse carbapenemase-producing Gram-negative bacteria collected from clinical s les in Victoria, Australia, containing KPC, GES, SME, OXA-23 and OXA-48-like carbapenemases were tested for susceptibility to CZA using the broth microdilution (BMD), Etest and disk diffusion methods. All isolates were susceptible to CZA. Etest correlated well with BMD, although Etest minimum inhibitory concentrations (MICs) were generally lower than BMD. Disk diffusion correlated moderately well with BMD, with two interpretive errors. This study confirms phenotypic CZA susceptibility in the carbapenemase groups tested, including the less common OXA-23-producing Escherichia coli, SME-producing Serratia marcescens and GES-5-producing Pseudomonas aeruginosa.
Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing
Publisher: American Society for Microbiology
Date: 27-02-2019
Abstract: The study results reported here perfectly demonstrate the power and promise of clinical metagenomics to recover genome sequences of important drug-resistant bacteria and to rapidly provide rich data that inform outbreak investigations and treatment decisions, independently of the need to culture the organisms.
Effectiveness of diet quality indices in measuring a change in diet quality over time: a systematic review and meta-analysis of randomized controlled trials
Publisher: Oxford University Press (OUP)
Date: 14-09-2023
Abstract: Diet quality indices (DQIs) were developed to score and rank adherence to dietary patterns in observational studies, but their use to measure changes in diet quality in intervention trials is becoming common in the literature. This systematic review and meta-analysis aimed to assess the effectiveness of DQIs to measure change in diet quality in intervention trials. MEDLINE, CINAHL, Embase, and the Cochrane Central Register of Controlled Trials databases were searched from January 1994 to June 2020. Two reviewers independently completed full-text screening. Eligible studies were randomized controlled trials that used validated a priori DQIs to measure change in diet quality in adults. Data were extracted by an independent reviewer and reviewed by the research team. Risk of bias was assessed by the Cochrane Collaboration’s Risk of Bias 2.0 tool. The 34 included studies (52% of reviewed studies, 0.6% of initially identified studies) used 10 different DQIs, 7 of which were able to measure significant change in diet quality. Meta-analyses of pooled results demonstrated change in the Healthy Eating Index (MD 5.35 95%CI, 2.74–7.97 P & 0.001) and the Mediterranean Dietary Adherence Screener (MD 1.61 95%CI, 1.00–2.23 P & 0.001) scores. DQIs were more likely to measure change in diet quality if they reflected the diet pattern being implemented, if the intervention was significantly different from the baseline and control diets, and if the study was adequately powered to detect change. DQIs are responsive to change in diet quality in intervention trials when the index used reflects the dietary changes made and the study is adequately powered. The appropriate selection of a DQI to suitably match dietary changes and study populations is important for future dietary intervention trials. PROSPERO registration no. CRD42020181357.
Vancomycin-resistant Enterococcus faecium sequence type 796 - rapid international dissemination of a new epidemic clone
Publisher: Springer Science and Business Media LLC
Date: 22-03-2018
DOI: 10.1186/S13756-018-0335-Z
Abstract: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates’ antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited ersity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized in iduals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.
Significant Variability exists in the Toxicity of Global Methicillin-resistant Staphylococcus aureus Lineages
Publisher: Cold Spring Harbor Laboratory
Date: 16-07-2021
DOI: 10.1101/2021.07.16.452633
Abstract: Staphylococcus aureus is a major human pathogen where the emergence of antibiotic resistant lineages, such as methicillin-resistant S. aureus (MRSA), is a major health concern. While some MRSA lineages are restricted to the healthcare setting, the epidemiology of MRSA is changing globally, with the rise of specific lineages causing disease in healthy people in the community. In the past two decades, community-associated MRSA (CA-MRSA) has emerged as a clinically important and virulent pathogen associated with serious skin and soft-tissue infections (SSTI). These infections are primarily toxin driven, leading to the suggestion that hyper-virulent lineages/multi-locus sequence types (STs) exist. To examine this, we compared the toxic activity of 475 MRSA isolates representing five major MRSA STs (ST22, ST93, ST8, ST239 and ST36) by employing a monocyte-macrophage THP-1 cell line as a surrogate for measuring gross cytotoxicity. We demonstrate that while certain MRSA STs contain highly toxic isolates, there is such variability within lineages to suggest that this aspect of virulence should not be inferred from the genotype of any given isolate. Furthermore, by interrogating the accessory gene regulator (Agr) sequences in this collection we identified several Agr mutations that were associated with reduced toxicity. Interestingly, the majority of isolates that were attenuated in toxin production contained no mutations in the agr locus, indicating a role of other undefined genes in S. aureus toxin regulation.
Detection of Streptococcus pyogenes M1UK in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA
Publisher: Springer Science and Business Media LLC
Date: 24-02-2023
DOI: 10.1038/S41467-023-36717-4
Abstract: A new variant of Streptococcus pyogenes serotype M1 (designated ‘M1 UK ’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor S. pyogenes ‘M1 global ’ and M1 UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1 UK in Australia, now isolated from the majority of serious infections caused by serotype M1 S. pyogenes . M1 UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing S. pyogenes in Asia. A single SNP in the 5’ transcriptional leader sequence of the transfer-messenger RNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator read-through in the M1 UK lineage. This represents a previously unappreciated mechanism of toxin expression and urges enhanced international surveillance.
Accurate Assessment of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Nasal Carriage
Publisher: Oxford University Press (OUP)
Date: 10-2005
DOI: 10.1086/444382
Weight Loss, Adipokines, and Quality of Life After Sleeve Gastrectomy in Obese Patients With Stages 3-4 CKD: A Randomized Controlled Pilot Study
Publisher: Elsevier BV
Date: 10-2014
Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei
Publisher: Springer Science and Business Media LLC
Date: 23-10-2019
DOI: 10.1038/S41467-019-12823-0
Abstract: Shigella sonnei increasingly dominates the international epidemiological landscape of shigellosis. Treatment options for S. sonnei are dwindling due to resistance to several key antimicrobials, including the fluoroquinolones. Here we analyse nearly 400 S. sonnei whole genome sequences from both endemic and non-endemic regions to delineate the evolutionary history of the recently emergent fluoroquinolone-resistant S. sonnei . We reaffirm that extant resistant organisms belong to a single clonal expansion event. Our results indicate that sequential accumulation of defining mutations ( gyrA -S83L, parC -S80I, and gyrA -D87G) led to the emergence of the fluoroquinolone-resistant S. sonnei population around 2007 in South Asia. This clone was then transmitted globally, resulting in establishments in Southeast Asia and Europe. Mutation analysis suggests that the clone became dominant through enhanced adaptation to oxidative stress. Experimental evolution reveals that under fluoroquinolone exposure in vitro, resistant S. sonnei develops further intolerance to the antimicrobial while the susceptible counterpart fails to attain complete resistance.
RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3′UTR required for intermediate vancomycin resistance
Publisher: Springer Science and Business Media LLC
Date: 22-06-2022
DOI: 10.1038/S41467-022-31177-8
Abstract: Treatment of methicillin-resistant Staphylococcus aureus infections is dependent on the efficacy of last-line antibiotics including vancomycin. Treatment failure is commonly linked to isolates with intermediate vancomycin resistance (termed VISA). These isolates have accumulated point mutations that collectively reduce vancomycin sensitivity, often by thickening the cell wall. Changes in regulatory small RNA expression have been correlated with antibiotic stress in VISA isolates however the functions of most RNA regulators is unknown. Here we capture RNA–RNA interactions associated with RNase III using CLASH. RNase III-CLASH uncovers hundreds of novel RNA–RNA interactions in vivo allowing functional characterisation of many sRNAs for the first time. Surprisingly, many mRNA–mRNA interactions are recovered and we find that an mRNA encoding a long 3′ untranslated region (UTR) (termed vigR 3′UTR) functions as a regulatory ‘hub’ within the RNA–RNA interaction network. We demonstrate that the vigR 3′UTR promotes expression of folD and the cell wall lytic transglycosylase isaA through direct mRNA–mRNA base-pairing. Deletion of the vigR 3′UTR re-sensitised VISA to glycopeptide treatment and both isaA and vigR 3′UTR deletions impact cell wall thickness. Our results demonstrate the utility of RNase III-CLASH and indicate that S. aureus uses mRNA-mRNA interactions to co-ordinate gene expression more widely than previously appreciated.
Prospective Comparison of the Clinical Impacts of Heterogeneous Vancomycin-Intermediate Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Susceptible MRS
Publisher: American Society for Microbiology
Date: 08-2009
DOI: 10.1128/AAC.01365-08
Abstract: Although methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (RVS-MRSA including vancomycin-intermediate S. aureus [VISA] and heterogeneous VISA [hVISA]) have been linked with vancomycin treatment failure, it is unclear whether they are more pathogenic than vancomycin-susceptible MRSA (VS-MRSA). We prospectively assessed patients with clinical MRSA isolates during a 10-month period to determine clinical status (infection versus colonization) and therapeutic outcome before correlating these findings with the results of detailed in vitro assessment of vancomycin susceptibility, including population analysis profile (PAP) testing. hVISA and VISA were defined by standard PAP criteria (area-under-the-curve ratio compared to that of the reference hVISA strain Mu3 [≥0.9]) and routine CLSI criteria (vancomycin MIC, 4 to 8 μg/ml), respectively. Among the 117 patients assessed, 58 had RVS-MRSA isolates (56 hVISA and 2 VISA) and 59 had VS-MRSA isolates the patient demographics and comorbidities were similar. RVS-MRSA was associated with a lower rate of infection than VS-MRSA (29/58 versus 46/59 P = 0.003), including a lower rate of bacteremia (3/58 versus 20/59, respectively P 0.001). The cure rates in RVS-MRSA and VS-MRSA groups were not statistically different (16/26 versus 31/42 P = 0.43), but the post hoc assessment of treatment regimes and study size made detailed conclusions difficult. The results of the macro method Etest correlated well with the PAP results (sensitivity, 98.3%, and specificity, 91.5%), but broth microdilution and our preliminary RVS-MRSA detection method correlated poorly. All isolates were susceptible to linezolid and daptomycin. These data suggest that detailed prospective laboratory identification of RVS-MRSA isolates may be of limited value and that, instead, such in vitro investigation should be reserved for isolates from patients who are failing appropriate anti-MRSA therapy.
Low mannose-binding lectin complement activation function is associated with predisposition to Legionnaires' disease
Publisher: Oxford University Press (OUP)
Date: 11-04-2007
DOI: 10.1111/J.1365-2249.2007.03390.X
Abstract: Innate immune system deficiency may predispose to severe infections such as Legionnaires' disease. We have investigated the role of mannose-binding lectin (MBL) deficiency in the Melbourne Aquarium Legionnaires' disease outbreak. Serum s les from patients and controls that were exposed but shown to be uninfected from the Melbourne Aquarium Legionnaires' disease outbreak were tested for MBL function (C4 deposition) and level (mannan-binding). MBL function was lower in Legionnaires' disease cases than in age- and sex-matched uninfected, exposed controls. The frequency of MBL deficiency with C4 deposition & 0·2 U/µl was significantly higher in Legionnaires' disease cases than in controls. This also applied to Legionnaires' disease cases requiring hospital care. There was no difference in MBL mannan-binding levels between Legionnaires' disease patients and controls. There was no significant interval change in MBL function or level after a mean of 46 days. MBL complement activation functional deficiency appears to predispose to Legionnaires' disease.
The Ionic Liquid Cholinium Arginate Is an Efficient Solvent for Extracting High-Value Nannochloropsis sp. Lipids
Publisher: American Chemical Society (ACS)
Date: 12-12-2019
Two novel point mutations in clinical Staphylococcus aureus reduce linezolid susceptibility and switch on the stringent response to promote persistent infection
Publisher: Public Library of Science (PLoS)
Date: 10-06-2010
Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307
Publisher: Cold Spring Harbor Laboratory
Date: 21-06-2018
DOI: 10.1101/352740
Abstract: Recent reports indicate the emergence of a new carbapenemase producing Klebsiella pneumoniae clone, ST307. Here we show that ST307 emerged in the mid-1990s (nearly 20 years prior to its first report), is already globally distributed and is intimately associated with a conserved plasmid harbouring the bla CTX-M-15 extended-spectrum beta-lactamase (ESBL) gene plus other antimicrobial resistance determinants. Our findings support the need for enhanced surveillance of this widespread ESBL clone in which carbapenem resistance is now emerging.
In vitro pharmacodynamics of colistin against multidrug-resistant Klebsiella pneumoniae
Publisher: Oxford University Press (OUP)
Date: 10-09-2008
DOI: 10.1093/JAC/DKN425
Abstract: Resistance to colistin is emerging in multidrug-resistant Gram-negative bacteria and no solid pharmacodynamic data are available for colistin against Klebsiella pneumoniae. Twenty-one multidrug-resistant clinical K. pneumoniae isolates from 16 different clinical sites worldwide were employed. The genetic relatedness of these isolates was examined with PFGE. In vitro pharmacodynamic properties of colistin (sulphate) were investigated by studying the MICs, mutation prevention concentrations, time-kill kinetics, population analysis profiles and the post-antibiotic effect (PAE). Time-kill was studied with three clinical isolates plus ATCC 13883 at concentrations ranging from 0.5 to 64x MIC. The PAE was examined after 20 min of exposure of these isolates. The 22 isolates belonged to 18 different PFGE groups. For susceptible isolates, colistin MICs ranged from 0.125 to 1 mg/L. Six isolates were colistin-resistant with MICs of >/=32 mg/L. Colistin heteroresistance was observed in 15 of 16 isolates considered colistin-susceptible based on MICs. For susceptible isolates, colistin showed extremely rapid killing however, regrowth was observed as early as 2 h after treatment and substantial regrowth at 24 h even at concentrations up to 64x MIC for some isolates. Colistin exhibited no or very modest PAE against the isolates tested. The data suggest that monotherapy with colistin methanesulfonate, the parenteral form of colistin, and long dosage intervals may be problematic for the treatment of infections caused by multidrug-resistant K. pneumoniae, particularly for colistin-heteroresistant strains. Further investigation on combination therapy of colistin with other antibiotics is warranted.
Genomic assessment of within-host population variation inNeisseria gonorrhoeae: Implications for gonorrhoea transmission
Publisher: Cold Spring Harbor Laboratory
Date: 31-08-2020
DOI: 10.1101/2020.08.24.20181230
Abstract: Mathematical modelling and genomic analyses are powerful methods for investigating the transmission dynamics of Neisseria gonorrhoeae , however, often make the implicit assumption that N. gonorrhoeae isolates at different anatomical sites within the same in idual are the same strain. In this study, two approaches were used to explore genetic ersity. First, we examined a collection of stored, clinical N. gonorrhoeae isolates sourced from multiple anatomical sites of single in iduals attending a sexual health clinic in Melbourne from 2011-2019. Second, we obtained multiple colony picks from primary clinical s les from in iduals attending a sexual health clinic in Melbourne from 2019-2020. Whole genome sequencing and a variety of bioinformatics approaches were used to determine both within-host and within-s le genetic ersity. Thirty-seven in iduals were identified that had cultured N. gonorrhoeae from two or more anatomical sites (urogenital, anorectal, or oropharyngeal), with a final dataset of 105 isolates. In 35/37 (94.6%) in iduals, infections were highly similar at the genetic level, with identical MLST and NG-MAST profiles. Pairwise comparisons of isolates within each in idual indicated that the maximum within-host pairwise SNP distance was 13 SNPs (median = 1, IQR: 0-3). Notably, four distinct multi-in idual phylogenetic clusters were identified, where the maximum pairwise SNP distance was 19 SNPs (median = 6, IQR = 2-11). Similarly, comparisons of isolates within each primary s le indicated that the maximum pairwise SNP distance was 8 SNPs (median = 2, IQR:1-3). This study suggests that in most cases of multi-site infection, the same strain of N. gonorrhoeae causes the infection at each anatomical site. However, WGS data alone cannot differentiate between the same infecting strain or (re)infections from the same transmission network. These data guide recommendations regarding optimal bioinformatic approaches to infer genetic relatedness of N. gonorrhoeae and will help inform future studies of gonorrhoea transmission and epidemiology. In most cases of multi-site infection, the same strain of N. gonorrhoeae causes infection at each anatomical site (urogenital, anorectal, and oropharyngeal) within an in idual. It is not possible, using genomics alone, to determine if an infection is from a single in idual or multiple in iduals within the same sexual network. Current literature reports an array of different bioinformatic methods for describing genetic ersity, highlighting that SNP thresholds are not directly transferable between studies.
Efficient Harvesting of Nannochloropsis Microalgae via Optimized Chitosan-Mediated Flocculation
Publisher: Wiley
Date: 21-09-2019
Translating genomics into practice for real-time surveillance and response to carbapenemase-producing Enterobacteriaceae: evidence from a complex multi-institutional KPC outbreak
Publisher: PeerJ
Date: 03-01-2028
DOI: 10.7717/PEERJ.4210
Abstract: Until recently, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae were rarely identified in Australia. Following an increase in the number of incident cases across the state of Victoria, we undertook a real-time combined genomic and epidemiological investigation. The scope of this study included identifying risk factors and routes of transmission, and investigating the utility of genomics to enhance traditional field epidemiology for informing management of established widespread outbreaks. All KPC-producing Enterobacteriaceae isolates referred to the state reference laboratory from 2012 onwards were included. Whole-genome sequencing was performed in parallel with a detailed descriptive epidemiological investigation of each case, using Illumina sequencing on each isolate. This was complemented with PacBio long-read sequencing on selected isolates to establish high-quality reference sequences and interrogate characteristics of KPC-encoding plasmids. Initial investigations indicated that the outbreak was widespread, with 86 KPC-producing Enterobacteriaceae isolates ( K. pneumoniae 92%) identified from 35 different locations across metropolitan and rural Victoria between 2012 and 2015. Initial combined analyses of the epidemiological and genomic data resolved the outbreak into distinct nosocomial transmission networks, and identified healthcare facilities at the epicentre of KPC transmission. New cases were assigned to transmission networks in real-time, allowing focussed infection control efforts. PacBio sequencing confirmed a secondary transmission network arising from inter-species plasmid transmission. Insights from Bayesian transmission inference and analyses of within-host ersity informed the development of state-wide public health and infection control guidelines, including interventions such as an intensive approach to screening contacts following new case detection to minimise unrecognised colonisation. A real-time combined epidemiological and genomic investigation proved critical to identifying and defining multiple transmission networks of KPC Enterobacteriaceae, while data from either investigation alone were inconclusive. The investigation was fundamental to informing infection control measures in real-time and the development of state-wide public health guidelines on carbapenemase-producing Enterobacteriaceae surveillance and management.
Rifampin resistance in staphylococcus epidermidis : molecular characterization and fitness cost of rpoB mutations
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.IJANTIMICAG.2017.12.019
Abstract: The molecular mechanisms and characteristics of rif icin (RIF) resistance in Staphylococcus epidermidis are poorly characterised, even though S. epidermidis is one of the most common nosocomial pathogens associated with indwelling medical device-related infections. The aim of this study was to investigate the evolution of RIF resistance and to characterise the associated molecular mechanisms in S. epidermidis. RIF-resistant mutants from two RIF-susceptible S. epidermidis strains (RP62A and IDRL-8883) were selected through in vitro and in vivo exposure to RIF. A total of 16 colonies with an RP62A background and 63 colonies with an IDRL-8883 background were analysed for rpoB mutations. The fitness of RIF-susceptible and isogenic RIF-resistant strains was assessed using a paired competition assay and by comparing generation times. All mutations detected were in cluster I of rpoB. The following five amino acid substitutions were selected in vitro: Asp471→Asn Asp471→Gly Asp471→Val Ser486→Tyr and His481→Tyr. The following three amino acid substitutions were selected in vivo: His481→Tyr Gln468→Lys and Ser486→Phe. Asp471→Asn and Asp471→Gly changes were associated with susceptible minimal inhibitory concentrations (MICs). In vitro competition assays revealed that all RIF-resistant mutants other than Ser486→Tyr and Ser486→Phe had a relative fitness of <1.0. His481→Tyr mutations had their own specific fitness costs and effects on growth rate, irrespective of strain background. In conclusion, the current study presents molecular characterisations and fitness costs of several rpoB mutations in S. epidermidis.
1,2,4-Oxadiazole antimicrobials act synergistically with daptomycin and display rapid kill kinetics against MDR Enterococcus faecium
Publisher: Oxford University Press (OUP)
Date: 06-03-2018
DOI: 10.1093/JAC/DKY064
Abstract: Enterococcus faecium is an important nosocomial pathogen. It has a high propensity for horizontal gene transfer, which has resulted in the emergence of MDR strains that are difficult to treat. The most notorious of these, vancomycin-resistant E. faecium, are usually treated with linezolid or daptomycin. Resistance has, however, been reported, meaning that new therapeutics are urgently needed. The 1,2,4-oxadiazoles are a recently discovered family of antimicrobials that are active against Gram-positive pathogens and therefore have therapeutic potential for treating E. faecium. However, only limited data are available on the activity of these antimicrobials against E. faecium. To determine whether the 1,2,4-oxadiazole antimicrobials are active against MDR and daptomycin-non-susceptible E. faecium. The activity of the 1,2,4-oxadiazole antimicrobials against vancomycin-susceptible, vancomycin-resistant and daptomycin-non-susceptible E. faecium was determined using susceptibility testing, time-kill assays and synergy assays. Toxicity was also evaluated against human cells by XTT and haemolysis assays. The 1,2,4-oxadiazoles are active against a range of MDR E. faecium, including isolates that display non-susceptibility to vancomycin and daptomycin. This class of antimicrobial displays rapid bactericidal activity and demonstrates superior killing of E. faecium compared with daptomycin. Finally, the 1,2,4-oxadiazoles act synergistically with daptomycin against E. faecium, with subinhibitory concentrations reducing the MIC of daptomycin for non-susceptible isolates to a level below the clinical breakpoint. The 1,2,4-oxadiazoles are active against MDR and daptomycin-non-susceptible E. faecium and hold great promise as future therapeutics for treating infections caused by these difficult-to-treat isolates.
An implementation science approach to evaluating pathogen whole genome sequencing in public health
Publisher: Springer Science and Business Media LLC
Date: 28-07-2021
DOI: 10.1186/S13073-021-00934-7
Abstract: Pathogen whole genome sequencing (WGS) is being incorporated into public health surveillance and disease control systems worldwide and has the potential to make significant contributions to infectious disease surveillance, outbreak investigation and infection prevention and control. However, to date, there are limited data regarding (i) the optimal models for integration of genomic data into epidemiological investigations and (ii) how to quantify and evaluate public health impacts resulting from genomic epidemiological investigations. We developed the Pathogen Genomics in Public HeAlth Surveillance Evaluation (PG-PHASE) Framework to guide examination of the use of WGS in public health surveillance and disease control. We illustrate the use of this framework with three pathogens as case studies: Listeria monocytogenes , Mycobacterium tuberculosis and SARS-CoV-2. The framework utilises an adaptable whole-of-system approach towards understanding how interconnected elements in the public health application of pathogen genomics contribute to public health processes and outcomes. The three phases of the PG-PHASE Framework are designed to support understanding of WGS laboratory processes, analysis, reporting and data sharing, and how genomic data are utilised in public health practice across all stages, from the decision to send an isolate or s le for sequencing to the use of sequence data in public health surveillance, investigation and decision-making. Importantly, the phases can be used separately or in conjunction, depending on the need of the evaluator. Subsequent to conducting evaluation underpinned by the framework, avenues may be developed for strategic investment or interventions to improve utilisation of whole genome sequencing. Comprehensive evaluation is critical to support health departments, public health laboratories and other stakeholders to successfully incorporate microbial genomics into public health practice. The PG-PHASE Framework aims to assist public health laboratories, health departments and authorities who are either considering transitioning to whole genome sequencing or intending to assess the integration of WGS in public health practice, including the capacity to detect and respond to outbreaks and associated costs, challenges and facilitators in the utilisation of microbial genomics and public health impacts.
Evolution of Daptomycin Resistance in Coagulase-Negative Staphylococci Involves Mutations of the Essential Two-Component Regulator WalKR
Publisher: American Society for Microbiology
Date: 03-2019
DOI: 10.1128/AAC.01926-18
Abstract: Coagulase-negative staphylococci (CoNS) represent one of the major causes of health care- and medical device-associated infections. Emerging antimicrobial resistance has complicated the treatment of systemic infections caused by CoNS.
Cytomegalovirus viral load monitoring after allogeneic bone marrow transplantation in patients receiving antiviral prophylaxis
Publisher: Springer Science and Business Media LLC
Date: 10-2003
Biosynthesis and Ether-Bridge Formation in Nargenicin Macrolides
Publisher: Wiley
Date: 11-02-2019
Abstract: The nargenicin family of antibiotics are macrolides containing a rare ether-bridged cis-decalin motif. Several of these compounds are highly active against multi-drug resistant organisms. Despite the identification of the first members of this family almost 40 years ago, the genetic basis for the production of these molecules and the enzyme responsible for formation of the oxa bridge, remain unknown. Here, the 85 kb nargenicin biosynthetic gene cluster was identified from a human pathogenic Nocardia arthritidis isolate and this locus is solely responsible for nargenicin production. Further investigation of this locus revealed a putative iron-α-ketoglutarate-dependent dioxygenase, which was found to be responsible for the formation of the ether bridge from the newly identified deoxygenated precursor, 8,13-deoxynargenicin. Uncovering the nargenicin biosynthetic locus provides a molecular basis for the rational bioengineering of these interesting antibiotic macrolides.
Author Correction: The evolution and international spread of extensively drug resistant Shigella sonnei
Publisher: Springer Science and Business Media LLC
Date: 21-04-2023
Evolution of multidrug resistance during staphylococcus aureus infection involves mutation of the essential two component regulator WalKR
Publisher: Public Library of Science (PLoS)
Date: 10-11-2011
Functional genomics reveals extensive diversity in Staphylococcus epidermidis restriction modification systems compared to Staphylococcus aureus
Publisher: Cold Spring Harbor Laboratory
Date: 22-05-2019
DOI: 10.1101/644856
Abstract: Staphylococcus epidermidis is a significant opportunistic pathogen of humans. Molecular studies in this species have been h ered by the presence of restriction-modification (RM) systems that limit introduction of foreign DNA. Here we establish the complete genomes and methylomes for seven clinically significant, genetically erse S. epidermidis isolates and perform the first systematic genomic analyses of the type I RM systems within both S. epidermidis and Staphylococcus aureus . Our analyses revealed marked differences in the gene arrangement, chromosomal location and movement of type I RM systems between the two species. Unlike S. aureus , S. epidermidis type I RM systems demonstrate extensive ersity even within a single genetic lineage. This is contrary to current assumptions and has important implications for approaching the genetic manipulation of S. epidermidis . Using Escherichia coli plasmid artificial modification (PAM) to express S. epidermidis hsdMS , we readily overcame restriction barriers in S. epidermidis , and achieved transformation efficiencies equivalent to those of modification deficient mutants. With these functional experiments we demonstrate how genomic data can be used to predict both the functionality of type I RM systems and the potential for a strain to be transformation proficient. We outline an efficient approach for the genetic manipulation of S. epidermidis from erse genetic backgrounds, including those that have hitherto been intractable. Additionally, we identified S. epidermidis BPH0736, a naturally restriction defective, clinically significant, multidrug-resistant ST2 isolate as an ideal candidate for molecular studies. Staphylococcus epidermidis is a major cause of hospital-acquired infections, especially those related to implanted medical devices. Understanding how S. epidermidis causes disease and devising ways to combat these infections has been hindered by an inability to genetically manipulate “hospital-adapted” strains that cause clinical disease. Here we provide the first comprehensive analyses of the mechanisms whereby S. epidermidis resists the uptake of foreign DNA and demonstrate that these are distinct from those described for S. aureus. Until now it had been assumed that these are the same. Using these insights, we demonstrate an efficient approach for the genetic manipulation of S. epidermidis to enable the study of clinically relevant isolates for the first time.
Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in Staphylococcus aureus
Publisher: American Society for Microbiology
Date: 11-02-2020
DOI: 10.1128/MSYSTEMS.00665-19
Abstract: Bacterial small RNAs (sRNAs) are RNA molecules that can have important regulatory roles across gene expression networks. There is a growing understanding of the scope and potential breadth of impact of sRNAs on global gene expression patterns in Staphylococcus aureus , a major human pathogen. Here, transcriptome comparisons were used to examine the roles of sRNA genes with a potential role in the response of S. aureus to antibiotic exposure. Although no measurable impact on key bacterial phenotypes was observed after deleting each of 18 sRNAs identified by these comparisons, this research is significant because it underscores the subtle modes of action of these sometimes abundant molecules within the bacterium.
Validation of a single-step, single-tube reverse transcription-loop-mediated isothermal amplification assay for rapid detection of SARS-CoV-2 RNA
Publisher: Cold Spring Harbor Laboratory
Date: 30-04-2020
DOI: 10.1101/2020.04.28.067363
Abstract: 2. The SARS-CoV-2 pandemic of 2020 has resulted in unparalleled requirements for RNA extraction kits and enzymes required for virus detection, leading to global shortages. This has necessitated the exploration of alternative diagnostic options to alleviate supply chain issues. To establish and validate a reverse transcription loop-mediated isothermal lification (RT-LAMP) assay for the detection of SARS-CoV-2 from nasopharyngeal swabs. We used a commercial RT-LAMP mastermix from OptiGene Ltd in combination with a primer set designed to detect the CDC N1 region of the SARS-CoV-2 nucleocapsid (N) gene. A single-tube, single-step fluorescence assay was implemented whereby as little as 1 μL of universal transport medium (UTM) directly from a nasopharyngeal swab could be used as template, bypassing the requirement for RNA purification. Amplification and detection could be conducted in any thermocycler capable of holding 65°C for 30 minutes and measure fluorescence in the FAM channel at one-minute intervals. Assay evaluation by assessment of 157 clinical specimens previously screened by E-gene RT-qPCR revealed assay sensitivity and specificity of 87% and 100%, respectively. Results were fast, with an average time-to-positive (Tp) for 93 clinical s les of 14 minutes (SD ±7 minutes). Using dilutions of SARS-CoV-2 virus spiked into UTM, we also evaluated assay performance against FDA guidelines for implementation of emergency-use diagnostics and established a limit-of-detection of 54 Tissue Culture Infectious Dose 50 per ml (TCID 50 mL −1 ), with satisfactory assay sensitivity and specificity. A comparison of 20 clinical specimens between four laboratories showed excellent interlaboratory concordance performing equally well on three different, commonly used thermocyclers, pointing to the robustness of the assay. With a simplified workflow, N1-STOP-LAMP is a powerful, scalable option for specific and rapid detection of SARS-CoV-2 and an additional resource in the diagnostic armamentarium against COVID-19. 3. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
Mortality and morbidity following exercise-based renal rehabilitation in patients with chronic kidney disease: the effect of programme completion and change in exercise capacity
Publisher: Oxford University Press (OUP)
Date: 15-02-2019
DOI: 10.1093/NDT/GFZ032
Emergence and global spread ofListeria monocytogenesmain clinical clonal complex
Publisher: Cold Spring Harbor Laboratory
Date: 20-12-2020
DOI: 10.1101/2020.12.18.423387
Abstract: Retracing microbial emergence and spread is essential to understanding the evolution and dynamics of pathogens. The bacterial foodborne pathogen Listeria monocytogenes clonal complex 1 ( Lm -CC1) is the most prevalent clonal group associated with listeriosis, and is strongly associated with cattle and dairy products. Here we analysed 2,021 Lm -CC1 isolates collected from 40 countries, since the first Lm isolation to the present day, to define its evolutionary history and population dynamics. Our results suggest that Lm -CC1 spread worldwide from North America following the Industrial Revolution through two waves of expansion, coinciding with the transatlantic livestock trade in the second half of the 19 th century and the rapid growth of cattle farming in the 20 th century. Lm -CC1 then firmly established at a local level, with limited inter-country spread. This study provides an unprecedented insight into Lm -CC1 phylogeography and dynamics and can contribute to effective disease surveillance to reduce the burden of listeriosis.
Comment on: Benchmarking of methods for identification of antimicrobial resistance genes in bacterial whole genome data
Publisher: Oxford University Press (OUP)
Date: 20-12-2017
DOI: 10.1093/JAC/DKW473
Staphylococcal superantigen-like protein 5 induces thrombotic and bleeding complications in vivo: Inhibition by an anti-SSL5 antibody and the glycan Bimosiamose
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1111/JTH.12022
Reply to De Angelis et al
Publisher: Oxford University Press (OUP)
Date: 31-05-2011
DOI: 10.1093/CID/CIR250
High-resolution melting genotyping of enterococcus faecium based on multilocus sequence typing derived single nucleotide polymorphisms
Publisher: Public Library of Science (PLoS)
Date: 16-12-2011
Antibiotic resistance and host immune evasion in Staphylococcus aureus mediated by a metabolic adaptation
Publisher: Proceedings of the National Academy of Sciences
Date: 11-02-2019
Abstract: Staphylococcus aureus is one of the most significant human bacterial pathogens that has the capacity to cause serious infections and become highly resistant to antibiotics. In this study, we identified a metabolic adaptation mechanism used by S. aureus to simultaneously circumvent killing by one of the last-line antistaphylococcal antibiotics, daptomycin, and attack from host innate immune cells. This process led to enhanced bacterial survival and was mediated by a change in bacterial membrane phospholipid composition sufficient to impair daptomycin membrane penetration and significantly affect neutrophil chemotactic responses. These results highlight the importance of bacterial membrane lipid adaptation in bacterial pathogenesis and provide crucial insights into potentially novel therapeutic targeting.
High performance enrichment-based genome sequencing to support the investigation of hepatitis A virus outbreaks
Publisher: Cold Spring Harbor Laboratory
Date: 21-07-2023
DOI: 10.1101/2023.07.21.548488
Abstract: Hepatitis A virus (HAV) infections are an increasing public health concern in low-endemicity regions due to outbreaks from foodborne infections and sustained transmission among vulnerable groups, including persons experiencing homelessness, those who inject drugs, and men who have sex with men (MSM), which is further compounded by aging, unvaccinated populations. DNA sequence characterisation of HAV for source tracking is performed by comparing small subgenomic regions of the virus. While this approach has been successful when robust epidemiological data are available, poor genetic resolution can lead to conflation of outbreaks with sporadic cases. HAV outbreak investigations would greatly benefit from the additional phylogenetic resolution obtained by whole virus genome sequence comparisons. However, HAV genomic approaches can be difficult because of challenges in isolating the virus, low sensitivity of direct metagenomic sequencing in complex s le matrices like various foods such as fruits, vegetables and molluscs, and difficulty designing highly multiplexed PCR primers across erse HAV genotypes. Here, we introduce a proof-of-concept pan- HAV oligonucleotide hybrid capture enrichment assay from serum and frozen berry specimens that yields complete and near-complete HAV genomes from as few as four input HAV genome copies. We used this method to recover HAV genomes from human serum specimens with high Cτ values (34·7—42·7), with high assay performance for all six human HAV sub-genotypes, both contemporary and historical. Our approach provides a highly sensitive and streamlined workflow for HAV WGS from erse s le types, that can be the basis for harmonised and high-resolution molecular epidemiology during HAV outbreak surveillance. This proof-of-concept study introduces a hybrid capture oligo panel for whole genome sequencing (WGS) of all six human pathogenic hepatitis A virus (HAV) sub-genotypes, exhibiting a higher sensitivity than some conventional genotyping assays. The ability of hybrid capture to enrich multiple targets allows for a single, streamlined workflow, thus facilitating the potential harmonization of molecular surveillance of HAV with other enteric viruses. Even challenging s le matrices can be accommodated, making it suitable for broad implementation in clinical and public health laboratories. This innovative approach has significant implications for enhancing multijurisdictional outbreak investigations, as well as our understanding of the global ersity and transmission dynamics of HAV.
Evidence for a new paradigm of gonorrhoea transmission: cross-sectional analysis of Neisseria gonorrhoeae infections by anatomical site in both partners in 60 male couples
Publisher: BMJ
Date: 17-04-2019
DOI: 10.1136/SEXTRANS-2018-053803
Abstract: Gonorrhoea transmission between men is currently thought to occur primarily to and from the urethra. Transmission without urethral involvement, from throat-to-throat and throat-to-anus, is considered to be uncommon. Using gonorrhoea results from male couples, we aimed to investigate the transmission dynamics of gonorrhoea. If current medical consensus is correct, then most throat and anal infections should be explained by the partner’s urethral infection. This is a cross-sectional analysis of gonorrhoea diagnosed by nucleic acid lification tests in both partners in male couples who attended Melbourne Sexual Health Centre together between March 2015 and June 2017. Isolates obtained from culture-positive infections underwent whole genome sequencing to assess phylogenetic relatedness between partners. In all 60 couples (120 men) at least one partner had gonorrhoea, and isolates had very high phylogenetic relatedness between partners. After excluding men with urethral gonorrhoea, among 32 men with anal gonorrhoea, 34% (95% CI 19% to 53 %) had a partner with throat gonorrhoea. After excluding couples where either man had urethral gonorrhoea, among 48 couples in which at least one man had throat gonorrhoea, in 23% (95% CI 12% to 37 %) of couples both men had throat gonorrhoea. The observed gonorrhoea positivity when urethral infection is absent supports a new paradigm of gonorrhoea transmission, where the throat is a major source of gonorrhoea transmission between men, through tongue kissing, oroanal sex and saliva use as anal lubricant. Public health messages may need to address the risk of saliva exposure during sex.
Clinical Relevance of Topical Antibiotic Use in Coselecting for Multidrug-Resistant Staphylococcus aureus: Insights from In Vitro and Ex Vivo
Publisher: American Society for Microbiology
Date: 19-04-2021
DOI: 10.1128/AAC.02048-20
Abstract: Topical antibiotic preparations, such as fusidic acid (FA) or mupirocin, are used in the prevention and treatment of superficial skin infections caused by staphylococci. Previous genomic epidemiology work has suggested an association between the widespread use of topical antibiotics and the emergence of methicillin-resistant Staphylococcus aureus in some settings.
Large tandem chromosome expansions facilitate niche adaptation during persistent infection with drug-resistant Staphylococcus aureus
Publisher: Microbiology Society
Date: 03-08-2015
Genomic Exploration of Within-Host Microevolution Reveals a Distinctive Molecular Signature of PersistentStaphylococcus aureusBacteraemia
Publisher: Cold Spring Harbor Laboratory
Date: 28-02-2018
DOI: 10.1101/273904
Abstract: Large-scale genomic studies of within-host evolution during Staphylococcus aureus bacteraemia (SAB) are needed to understanding bacterial adaptation underlying persistence and thus refining the role of genomics in management of SAB. However, available comparative genomic studies of sequential SAB isolates have tended to focus on selected cases of unusually prolonged bacteraemia, where secondary antimicrobial resistance has developed. To understand the bacterial genomic evolution during SAB more broadly, we applied whole genome sequencing to a large collection of sequential isolates obtained from patients with persistent or relapsing bacteraemia. We show that, while adapation pathways are heterogenous and episode-specific, isolates from persistent bacteraemia have a distinctive molecular signature, characterised by a low mutation frequency and high proportion of non-silent mutations. By performing an extensive analysis of structural genomic variants in addition to point mutations, we found that these often overlooked genetic events are commonly acquired during SAB. We discovered that IS 256 insertion may represent the most effective driver of within-host microevolution in selected lineages, with up to three new insertion events per isolate even in the absence of other mutations. Genetic mechanisms resulting in significant phenotypic changes, such as increases in vancomycin resistance, development of small colony phenotypes, and decreases in cytotoxicity, included mutations in key genes ( rpoB, stp, agrA ) and an IS256 insertion upstream of the walKR operon. This study provides for the first time a large-scale analysis of within-host evolution during invasive S. aureus infection and describes specific patterns of adaptation that will be informative for both understanding S. aureus pathoadaptation and utilising genomics for management of complicated S. aureus infections.
Emergence and divergence of major lineages of shiga-toxin-producing escherichia coli in Australia
Publisher: Microbiology Society
Date: 05-2019
Whole genome sequencing in clinical and public health microbiology.
Publisher: Elsevier BV
Date: 04-2015
The evolution of vancomycin intermediate Staphylococcus aureus (VISA) and heterogenous-VISA
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.MEEGID.2013.03.047
Abstract: Resistance to new antimicrobials is generally recognized in Staphylococcus aureus soon after they are released for clinical use. In the case of vancomycin, which was first released in the 1950s, resistance was not reported until the mid 1990s, with the description of vancomycin-intermediate S. aureus (VISA), and heterogenous-VISA (hVISA). Unraveling the complex genetic and cell wall structural changes conferring low-level vancomycin resistance in S. aureus has proved challenging. However the recent advances in high throughput whole-genome sequencing has played a key role in determining the breadth of bacterial chromosomal changes linked with resistance. Diverse mutations in a small number of staphylococcal regulatory genes, in particular walKR, graRS, vraSR and rpoB, have been associated with hVISA and VISA. Only a small number of these mutations have been experimentally proven to confer the resistance phenotype and some of these only partially contribute to resistance. It also appears that the evolution of VISA from VSSA is a step-wise process. Transcriptomics studies, and analysis of host pathogen interactions, indicate that the evolution of vancomycin-susceptible S. aureus to VISA is associated not only with antibiotic resistance, but with other changes likely to promote persistent infection. These include predicted alterations in central metabolism, altered expression of virulence associated factors, attenuated virulence in vivo, and alterations in susceptibility to host innate immune responses, together with reduced susceptibility to other antibiotics. In fact, current data suggests that hVISA and VISA represent a bacterial evolutionary state favoring persistence in the face of not only antibiotics, but also the host environment. The additional knowledge of staphylococcal biology that has been uncovered during the study of hVISA and VISA is significant. The present review will detail the current understanding of the evolutionary process in the generation of hVISA and VISA, and explore the erse additional changes that occur in these strains.
Biogas production coupled to repeat microalgae cultivation using a closed nutrient loop
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.BIORTECH.2018.05.039
Abstract: Anaerobic digestion is an established technology to produce renewable energy as methane-rich biogas for which microalgae are a suitable substrate. Besides biogas production, anaerobic digestion of microalgae generates an effluent rich in nutrients, so-called digestate, that can be used as a growth medium for microalgal cultures, with the potential for a closed nutrient loop and sustainable bioenergy facility. In this study, the methane potential and nutrient mobilization of the microalga Scenedemus dimorphus was evaluated under continuous conditions. The suitability of using the digestate as culture medium was also evaluated. The results show that S. dimorphus is a suitable substrate for anaerobic digestion with an average methane yield of 199 mL g
Elucidating the Pharmacokinetics/Pharmacodynamics of Aerosolized Colistin against Multidrug-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in a Mouse Lung Infection Model
Publisher: American Society for Microbiology
Date: 02-2018
DOI: 10.1128/AAC.01790-17
Abstract: The pharmacokinetics harmacodynamics (PK/PD) of aerosolized colistin was investigated against Acinetobacter baumannii and Klebsiella pneumoniae over 24 h in a neutropenic mouse lung infection model. Dose fractionation studies were performed over 2.64 to 23.8 mg/kg/day, and the data were fitted to a sigmoid inhibitory model. The area under the concentration-time curve over 24 h in the steady state ided by the MIC (AUC/MIC) in the epithelial lining fluid was the most predictive PK/PD index for aerosolized colistin against both pathogens. Our study provides important pharmacological information for optimizing aerosolized colistin.
Heart Rate Variability and Long Chain n-3 Polyunsaturated Fatty Acids in Chronic Kidney Disease Patients on Haemodialysis: A Cross-Sectional Pilot Study
Publisher: MDPI AG
Date: 18-07-2021
DOI: 10.3390/NU13072453
Abstract: Low heart rate variability (HRV) is independently associated with increased risk of sudden cardiac death (SCD) and all cardiac death in haemodialysis patients. Long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may exert anti-arrhythmic effects. This study aimed to investigate relationships between dialysis, sleep and 24 h HRV and LC n-3 PUFA status in patients who have recently commenced haemodialysis. A cross-sectional study was conducted in adults aged 40–80 with chronic kidney disease (CKD) stage 5 (n = 45, mean age 58, SD 9, 20 females and 25 males, 39% with type 2 diabetes). Pre-dialysis blood s les were taken to measure erythrocyte and plasma fatty acid composition (wt % fatty acids). Mean erythrocyte omega-3 index was not associated with HRV following adjustment for age, BMI and use of β-blocker medication. Higher ratios of erythrocyte eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) were associated with lower 24 h vagally-mediated beat-to-beat HRV parameters. Higher plasma EPA and docosapentaenoic acid (DPAn-3) were also associated with lower sleep-time and 24 h beat-to-beat variability. In contrast, higher plasma EPA was significantly related to higher overall and longer phase components of 24 h HRV. Further investigation is required to investigate whether patients commencing haemodialysis may have compromised conversion of EPA to DHA, which may impair vagally-mediated regulation of cardiac autonomic function, increasing risk of SCD.
Tracking the COVID-19 pandemic in Australia using genomics
Publisher: Springer Science and Business Media LLC
Date: 09-2020
DOI: 10.1038/S41467-020-18314-X
Abstract: Genomic sequencing has significant potential to inform public health management for SARS-CoV-2. Here we report high-throughput genomics for SARS-CoV-2, sequencing 80% of cases in Victoria, Australia (population 6.24 million) between 6 January and 14 April 2020 (total 1,333 COVID-19 cases). We integrate epidemiological, genomic and phylodynamic data to identify clusters and impact of interventions. The global ersity of SARS-CoV-2 is represented, consistent with multiple importations. Seventy-six distinct genomic clusters were identified, including large clusters associated with social venues, healthcare and cruise ships. Sequencing sequential s les from 98 patients reveals minimal intra-patient SARS-CoV-2 genomic ersity. Phylodynamic modelling indicates a significant reduction in the effective viral reproductive number ( R e ) from 1.63 to 0.48 after implementing travel restrictions and physical distancing. Our data provide a concrete framework for the use of SARS-CoV-2 genomics in public health responses, including its use to rapidly identify SARS-CoV-2 transmission chains, increasingly important as social restrictions ease globally.
Compliance With a Structured Weight Loss Program Is Associated With Reduced Systolic Blood Pressure in Obese Patients With Chronic Kidney Disease
Publisher: Oxford University Press (OUP)
Date: 21-06-2012
DOI: 10.1038/AJH.2012.80
Abstract: The effectiveness of lifestyle-based weight loss programs in obese patients with chronic disease has not been widely studied. This study examined the effectiveness of a weight management program (WMP), and sought to determine factors associated with successful weight loss in obese patients with chronic kidney disease (CKD). In this prospective cohort study, all patients with a body mass index (BMI) of >30 kg/m(2) referred to our clinic from January 2005 to December 2008 and who commenced a structured WMP of an energy-reduced renal diet, exercise, and pharmacotherapy were included in the analyses. Changes in body weight and associated variables up to 24 months were assessed with intention-to-treat mixed linear models and predictors of weight loss were identified with multiple linear regression. One hundred and thirty-five patients (56% male), of mean age 52.2 years and BMI 36.4 kg/m(2) commenced the WMP. Significant weight loss was achieved for all patients at 6, 12, 18, and 24 months. Weight loss at 12 months was predicted by compliance and age, but not by baseline BMI, blood pressure (BP), stage of CKD or pharmacotherapy use. Greater compliance was associated with decreased systolic BP, with no change in mean antihypertensive medication dose. Significant weight loss was achieved, demonstrating the effectiveness of the WMP, and compliance with a structured program improved weight loss and systolic BP.
A Potential Blind Spot in Vancomycin Treatment Studies
Publisher: Oxford University Press (OUP)
Date: 29-03-2012
DOI: 10.1093/CID/CIS333
Development of Phylodynamic Methods for Bacterial Pathogens
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.TIM.2021.02.008
Abstract: Phylodynamic methods have been essential to understand the interplay between the evolution and epidemiology of infectious diseases. To date, the field has centered on viruses. Bacterial pathogens are seldom analyzed under such phylodynamic frameworks, due to their complex genome evolution and, until recently, a paucity of whole-genome sequence data sets with rich associated metadata. We posit that the increasing availability of bacterial genomes and epidemiological data means that the field is now ripe to lay the foundations for applying phylodynamics to bacterial pathogens. The development of new methods that integrate more complex genomic and ecological data will help to inform public heath surveillance and control strategies for bacterial pathogens that represent serious threats to human health.
Multi-Site Assessment of Rapid, Point-of-Care Antigen Testing for the Diagnosis of SARS-CoV-2 Infection in a Low-Prevalence Setting: A Validation and Implementation Study
Publisher: Elsevier BV
Date: 2021
DOI: 10.2139/SSRN.3750715
Implementation and evaluation of a novel real-time multiplex assay for SARS-CoV-2: In-field learnings from a clinical microbiology laboratory
Publisher: Cold Spring Harbor Laboratory
Date: 05-06-2020
DOI: 10.1101/2020.06.03.20117267
Abstract: The unprecedented scale of testing required to effectively control the coronavirus disease (COVID-19) pandemic has necessitated urgent implementation of rapid testing in clinical microbiology laboratories. To date, there are limited data available on the analytical performance of emerging commercially available assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and integration of these assays into laboratory workflows. Here, we performed a prospective validation study of a commercially available assay, the AusDiagnostics Coronavirus Typing (8-well) assay. Respiratory tract s les for SARS-CoV-2 testing were collected between 1 st March and 25 th March 2020. All positive s les and a random subset of negative s les were sent to a reference laboratory for confirmation. In total, 2,673 s les were analyzed using the Coronavirus Typing assay. The predominant s le type was a combined nasopharyngeal/throat swab (2,640/2,673 98.8%). Fifty-four patients were positive for SARS-CoV-2 (0.02%) using the Coronavirus Typing assay 53/54 (98.1%) positive results and 621/621 (100%) negative results were concordant with the reference laboratory. Compared to the reference standard, sensitivity of the Coronavirus Typing assay for SARS-CoV-2 was 100% [95% CI 93.2%-100%], specificity 99.8% [95% CI 99.1%-100%], positive predictive value 98.1% (95% CI 90.2%-99.7%] and negative predictive value 100% [95% CI 99.4%-100%]. In many countries, standard regulatory requirements for the introduction of new assays have been replaced by emergency authorizations and it is critical that laboratories share their post-market validation experiences, as the consequences of widespread introduction of a sub-optimal assay for SARS-CoV-2 are profound. Here, we share our in-field experience, and encourage other laboratories to follow suit.
Publisher Correction: RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3′UTR required for intermediate vancomycin resistance
Publisher: Springer Science and Business Media LLC
Date: 27-09-2022
Control Of Isometric Muscle Activity In Cerebral Palsy
Publisher: Wiley
Date: 09-1990
DOI: 10.1111/J.1469-8749.1990.TB08481.X
Abstract: Voluntary control of muscle contraction was examined in five adults with cerebral palsy, who were required to track a moving target by continuously varying the level of isometric contraction of elbow flexor muscles (measured by EMG). First performance varied from minimal control to almost normal control, depending on the severity of disability. Practice over 12 weeks reduced inappropriate muscle activity in the most disabled patients, but there was no increase in appropriate muscle activity for any patient beyond that observed after the first few minutes of tracking. Thus their ability to translate a visual response into the appropriate motor activity was impaired, and there was no evidence of potential to overcome this. This supports the authors' earlier proposal that impairment of sensory-motor learning is the primary cause of functional disability in cerebral palsy. The EMG tracking task may provide a technique for assessing the ability of in iduals with cerebral palsy to control muscle contraction.
Impact of vanB vancomycin-resistant enterococcal bacteraemia analysed as a time-varying covariate on length of hospital stay
Publisher: Cambridge University Press (CUP)
Date: 19-02-2014
DOI: 10.1017/S095026881400020X
Abstract: The impact of vanB vancomycin-resistant enterococci (VRE) bacteraemia on length of stay (LOS) in hospital, after adjusting for the time-varying nature of enterococcal bacteraemia (variable onset of bacteraemia post-admission), is unknown. Survival analyses (time-varying Cox and competing risks regression) were performed on vanB VRE bacteraemia patients, matched 1:1 with vancomycin-susceptible enterococci bacteraemia patients to determine the factors associated with LOS in these patients. In Cox regression analysis, vanB VRE bacteraemia, intensive-care-unit admission, Charlson co-morbidity index score ⩾4, and an increase in the time to receive appropriate antibiotics were associated with prolonged LOS. Competing risks regression which accounts for the influence of in-patient mortality on the ability to observe the event discharge alive from hospital suggests that, vanB VRE bacteraemia was not significantly associated with prolonged LOS. For the first time, the rate of discharge from hospital in patients with vanB VRE bacteraemia has been quantified.
Population genomics provides insights in diversity, epidemiology, evolution and pathogenicity of the waterborne pathogen Mycobacterium kansasii
Publisher: Research Square Platform LLC
Date: 10-2020
DOI: 10.21203/RS.3.RS-78954/V1
Abstract: Mycobacterium kansasii is a nontuberculous mycobacterium that can cause serious pulmonary disease. Genotyping suggested that the species is composed of at least six subtypes that vary in clinical significance, with subtype I being clinically dominant but less commonly isolated from environmental sources. Here we report a population genomics study of 358 M. kansasii isolates obtained from global water and clinical sources. Phylogenomic analyses revealed that the six subtypes are more accurately designated as closely related subspecies. These subspecies show le evidence of recombination mediated by distributive conjugative transfer that has contributed to subspeciation and on-going ersification. Water was confirmed as a source of clinical infections by showing that genomes of clinical strains from an Australian outbreak were almost indistinguishable from strains contaminating the drinking water supply. Most clinical infections (nearly 80%) were due to a recently emerged group of strains designated the M. kansasii main complex (MKMC), which appears to have originated in Europe in 1900s and expanded globally over the past century. Comparative genomic analyses revealed that the MKMC has maintained the methylcitrate cycle and expanded ESX-I secretion-associated proteins, perhaps facilitating metabolic adaptation and pathogenicity for human hosts. Evidence of on-going positive selection in isolates of the MKMC was found in genes involved in carbon and secondary metabolism, metal ion homeostasis and cell surface remodeling that could represent adaptation to human hosts. These results further our understanding of the epidemiology and pathogenicity of M. kansasii and emphasize the importance of monitoring its potential transition to a more human-adapted pathogen.
Functional analysis of the first complete genome sequence of a multidrug resistant sequence type 2 Staphylococcus epidermidis
Publisher: Microbiology Society
Date: 20-09-2016
Prevalence of genital and oropharyngeal chlamydia and gonorrhoea among female sex workers in Melbourne, Australia, 2015–2017: need for oropharyngeal testing
Publisher: BMJ
Date: 21-05-2019
DOI: 10.1136/SEXTRANS-2018-053957
Abstract: The Victorian legislation requires sex workers to have quarterly screening for genital chlamydia and gonorrhoea, but screening for oropharyngeal infection is not mandatory in Victoria, Australia. In 2017, oropharyngeal screening for gonorrhoea and chlamydia was added as part of the routine quarterly screening for sex workers attending the Melbourne Sexual Health Centre (MSHC). The aim of this study was to examine the prevalence of oropharyngeal gonorrhoea and chlamydia among female sex workers (FSW). We included females who (1) self-identified as sex workers or were attended MSHC for a sex work certificate and (2) had tested for any STI or HIV, between March 2015 and December 2017. The prevalence of HIV, syphilis, chlamydia and gonorrhoea was calculated. There were 8538 FSW consultations among 2780 in iduals during the study period. There was a twofold increase in genital gonorrhoea (from 0.5% (95% CI 0.3% to 0.9%) to 1.1% (95% CI 0.8% to 1.5%) p trend =0.047) and a 1.5-fold increase in genital chlamydia (from 2.2% (95% CI 1.6% to 2.8%) to 3.2% (95% CI 2.6% to 3.8%) p trend =0.031) during the period. Overall, the prevalence of HIV (0.2% (95% CI 0.1% to 0.3%)) and syphilis (0.1% (95% CI 0.0% to 0.2%)) remained low and did not change over time. In 2017, the prevalence of oropharyngeal gonorrhoea was 2.0% (95% CI 1.6% to 2.6%) and oropharyngeal chlamydia was 2.1% (95% CI 1.6% to 2.7%). Among FSW who were tested positive for gonorrhoea and chlamydia, 55% (n=41) and 34% (n=45) only tested positive in the oropharynx but not genital for gonorrhoea and chlamydia, respectively. The prevalence of oropharyngeal gonorrhoea and chlamydia is similar to the prevalence at genital sites and is often independent of genital infection. It is important to test the oropharynx and genital site for chlamydia and gonorrhoea among FSW.
Phasevarion-regulated virulence in the emerging pediatric pathogen Kingella kingae
Publisher: American Society for Microbiology
Date: 12-2017
DOI: 10.1128/IAI.00319-17
Abstract: Kingella kingae is a common etiological agent of pediatric osteoarticular infections. While current research has expanded our understanding of K. kingae pathogenesis, there is a paucity of knowledge about host-pathogen interactions and virulence gene regulation. Many host-adapted bacterial pathogens contain phase variable DNA methyltransferases ( mod genes), which can control expression of a regulon of genes (phasevarion) through differential methylation of the genome. Here, we identify a phase variable type III mod gene in K. kingae , suggesting that phasevarions operate in this pathogen. Phylogenetic studies revealed that there are two active modK alleles in K. kingae . Proteomic analysis of secreted and surface-associated proteins, quantitative PCR, and a heat shock assay comparing the wild-type modK1 ON (i.e., in frame for expression) strain to a modK1 OFF (i.e., out of frame) strain revealed three virulence-associated genes under ModK1 control. These include the K. kingae toxin rtxA and the heat shock genes groEL and dnaK . Cytokine expression analysis showed that the interleukin-8 (IL-8), IL-1β, and tumor necrosis factor responses of THP-1 macrophages were lower in the modK1 ON strain than in the modK1 :: kan mutant. This suggests that the ModK1 phasevarion influences the host inflammatory response and provides the first evidence of this phase variable epigenetic mechanism of gene regulation in K. kingae .
Unintentional Weight Loss Is an Independent Predictor of Mortality in a Hemodialysis Population
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1053/J.JRN.2010.04.003
Abstract: This study investigated common components of classification of nutrition screening risk in the prediction of clinical end-points (mortality and morbidity) in hemodialysis patients over a 3-year period (2005 to 2008). This was a retrospective cohort study. This study was conducted at a Hemodialysis centre. The study included patients on maintenance hemodialysis in June 2005. Assessment of nutrition risk was carried out using components of Protein-Energy Wasting criteria. Clinical outcome at the 3-year follow-up (June 2008) was measured as mortality and morbidity (as unplanned hospital admissions). Risk of mortality was investigated independent of comorbidities, age, gender, ethnicity, and dialysis vintage using Cox proportional hazards model. A total of 217 patients met the inclusion criteria (143 male [66%] age, 60.5 ± 15.6 years). Patients who lost ≥5% body weight in the 6 months before the study commenced, had a 3-fold (Hazard Ratio = 3.0 95% confidence interval: 1.2 to 7.5) independent greater risk of death (P = .02). Low serum albumin (<38 g/L) resulted in higher morbidity and mortality however, this was not statistically significant when adjusted for confounders. Body mass index was only available in 64% (138 of 217) of the cohort at baseline, and was not related to clinical outcome at the 3-year follow-up. Unintentional weight loss is independently predictive of clinical outcome in this cohort of dialysis patients. It is recommended that nutrition screening tools include weight loss as a key component in classification of risk and for prioritizing patient care.
Comparison of contemporary invasive and non-invasive Streptococcus pneumoniae isolates reveals new insights into circulating anti-microbial resistance determinants
Publisher: American Society for Microbiology
Date: 12-10-2023
DOI: 10.1128/AAC.00785-23
A multicentre double-blind randomised controlled trial evaluating the efficacy of daily use of antibacterial mouthwash against oropharyngeal gonorrhoea among men who have sex with men: the OMEGA (Oral
Publisher: Springer Science and Business Media LLC
Date: 28-06-2017
Incursions of Candida auris into Australia, 2018
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 06-2020
The delivery of patient centred dietetic care in subacute rehabilitation units: A scoping review
Publisher: Wiley
Date: 07-2021
Comparison of the Xpert Methicillin-Resistant Staphylococcus aureus (MRSA) Assay, BD GeneOhm MRSA Assay, and Culture for Detection of Nasal and Cutaneous Groin Colonizat
Publisher: American Society for Microbiology
Date: 11-2009
DOI: 10.1128/JCM.00303-09
Abstract: Detection of methicillin (meticillin)-resistant Staphylococcus aureus colonization was assessed using combined nose and groin swabs in two commercial PCR assays (the Xpert MRSA assay and the BD GeneOhm MRSA assay). Compared to routine culture, both had similar sensitivities (87.0% versus 84.8%, respectively) and specificities (93.8% versus 92.7%, respectively). Combined PCR assays provide a rapid and more-complete assessment of colonization at a cost similar to that of single-site analysis.
The importance of regulatory RNAs in Staphylococcus aureus
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.MEEGID.2013.11.016
Abstract: RNA molecules with regulatory functions in pathogenic bacteria have benefited from a renewed interest these two last decades. In Staphylococcus aureus, recent genome-wide approaches have led to the discovery that almost 10-20% of genes code for RNAs with critical regulatory roles in adaptive processes. These RNAs include trans-acting RNAs, which mostly act through binding to target mRNAs, and cis-acting RNAs, which include regulatory regions of mRNAs responding to various metabolic signals. Besides recent analysis of S. aureus transcriptome has revealed an unprecedented existence of pervasive transcription generating a high number of weakly expressed antisense RNAs along the genome as well as numerous mRNAs with overlapped regions. Here, we will illustrate the ersity of trans-acting RNAs and illustrate how they are integrated into complex regulatory circuits, which link metabolism, stress response and virulence.
Remodeling of pSK1 family plasmids and enhanced chlorhexidine tolerance in a dominant hospital lineage of methicillin-resistant staphylococcus aureus
Publisher: American Society for Microbiology
Date: 05-2019
DOI: 10.1128/AAC.02356-18
Abstract: Staphylococcus aureus is a significant human pathogen whose evolution and adaptation have been shaped in part by mobile genetic elements (MGEs), facilitating the global spread of extensive antimicrobial resistance. However, our understanding of the evolutionary dynamics surrounding MGEs, in particular, how changes in the structure of multidrug resistance (MDR) plasmids may influence important staphylococcal phenotypes, is incomplete.
Bridging of Neisseria gonorrhoeae lineages across sexual networks in the HIV pre-exposure prophylaxis era
Publisher: Springer Science and Business Media LLC
Date: 05-09-2019
DOI: 10.1038/S41467-019-12053-4
Abstract: Whole genome sequencing (WGS) has been used to investigate transmission of Neisseria gonorrhoeae , but to date, most studies have not combined genomic data with detailed information on sexual behaviour to define the extent of transmission across population risk groups (bridging). Here, through combined epidemiological and genomic analysis of 2,186 N. gonorrhoeae isolates from Australia, we show widespread transmission of N. gonorrhoeae within and between population groups. We describe distinct transmission clusters associated with men who have sex with men (MSM) and heterosexuals, and men who have sex with men and women (MSMW) are identified as a possible bridging population between these groups. Further, the study identifies transmission of N. gonorrhoeae between HIV-positive and HIV-negative in iduals receiving pre-exposure prophylaxis (PrEP). Our data highlight several groups that can be targeted for interventions aimed at improving gonorrhoea control, including returning travellers, sex workers, and PrEP users.
Clinical manifestations of invasive meningococcal disease in Victoria with the emergence of serogroup W and serogroup Y Neisseria meningitidis
Publisher: Wiley
Date: 03-2021
DOI: 10.1111/IMJ.14771
NGMASTER:in silico multi-antigen sequence typing for Neisseria gonorrhoeae
Publisher: Microbiology Society
Date: 25-08-2016
Author response: Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Publisher: eLife Sciences Publications, Ltd
Date: 03-07-2023
Genomics for Molecular Epidemiology and Detecting Transmission of Carbapenemase-Producing Enterobacterales in Victoria, Australia, 2012 to 2016
Publisher: American Society for Microbiology
Date: 09-2019
DOI: 10.1128/JCM.00573-19
Abstract: Carbapenemase-producing Enterobacterales (CPE) are being increasingly reported in Australia, and integrated clinical and genomic surveillance is critical to effectively manage this threat. We sought to systematically characterize CPE in Victoria, Australia, from 2012 to 2016.
Isolation and rapid sharing of the 2019 novel coronavirus (
SARS
‐CoV‐2) from the first patient diagnosed with
COVID
‐19 in Austra
Publisher: AMPCo
Date: 04-2020
DOI: 10.5694/MJA2.50569
Obesity Does Not Influence Hepcidin and Hemojuvelin Levels in Hemodialysis Patients
Publisher: S. Karger AG
Date: 12-12-2013
DOI: 10.1159/000355545
Abstract: b i Background/Aims: /i /b Clinical studies have shown increased levels of hepcidin causing functional iron deficiency in obese in iduals. This study examined whether obesity contributes to increased hepcidin and hemojuvelin levels in adult hemodialysis patients. b i Methods: /i /b In a case-control design, 37 obese [body mass index (BMI) kg/m sup /sup ] stable hemodialysis patients and 37 patients with normal BMI (20-25 kg/m sup /sup ), matched for age, gender and race, who fulfilled a strict set of inclusion and exclusion criteria were included in the study. Serum hepcidin and hemojuvelin, markers of iron status and inflammation, and routine hematological and biochemical variables were measured on s les obtained prior to the midweek hemodialysis session. b i Results: /i /b Obese and nonobese patients (BMI 35.1 ± 3.4 vs. 22.8 ± 1.4 kg/m sup /sup p 0.001) were similar with regard to basic comorbidities and use of erythropoietin and iron. Levels of hemoglobin, hypochromic red cells and reticulocytes were similar in the two groups. Serum iron and transferrin saturation levels were on the low side and not different between obese and lean in iduals total iron-binding capacity showed a trend towards higher levels in obese patients (48.4 ± 8.3 vs. 44.9 ± 7.4 μmol/l p = 0.065). Levels of serum ferritin (651 ± 302 vs. 705 ± 327 μg/l p = 0.46), hepcidin (118.3 ± 67.7 vs. 119.3 ± 78.0 ng/ml p = 0.95) and hemojuvelin (1.90 ± 1.11 vs. 1.94 ± 1.24 mg/l p = 0.90) were high but similar between the two groups. Serum hepcidin showed a significant correlation only with ferritin (r = 0.287, p = 0.013). b i Conclusions: /i /b Hepcidin and hemojuvelin levels are already considerably elevated in dialysis patients, but obesity does not have an additional impact. Further studies should examine whether increased weight contributes towards hepcidin elevation in predialysis in iduals, in whom there is a lesser burden of systemic inflammation.
Blue Skies beyond COVID-19 at the Queensland University of Technology
Publisher: Wiley
Date: 07-2021
The RpoB H{481}Y rifampicin resistance mutation and an active stringent response reduce virulence and increase resistance to innate immune responses in Staphylococcus aureus
Publisher: Oxford University Press (OUP)
Date: 18-12-2013
The Molecular Epidemiology of the Highly Virulent ST93 Australian Community Staphylococcus aureus Strain
Publisher: Public Library of Science (PLoS)
Date: 10-08-2012
Bioinformatic investigation of discordant sequence data for SARS-CoV-2: insights for robust genomic analysis during pandemic surveillance
Publisher: Cold Spring Harbor Laboratory
Date: 02-02-2023
DOI: 10.1101/2023.02.01.526694
Abstract: The capacity to undertake whole genome sequencing (WGS) in public health laboratories (PHLs) has grown rapidly in response to COVID-19, and SARS-CoV-2 genomic data has been invaluable for managing the pandemic. The public health response has been further supported by the rapid upgrade and implementation of laboratory and bioinformatic resources. However, there remains a high degree of variability in methods and capabilities between laboratories. In addition to evolving methodology and improved understanding of SARS-CoV-2, public health laboratories have become strained during surges in case numbers, adding to the difficulty of ensuring the highest data accuracy. Here, we formed a national working group comprised of laboratory scientists and bioinformaticians from Australia and New Zealand to improve data concordance across PHLs. Through investigating discordant sequence data from Australia’s first external SARS-CoV-2 WGS proficiency testing program (PTP), we show that most discrepancies in genome assessment arose from intrahost variation. While others could be remedied using reasonable, parsimonious bioinformatic quality control. Furthermore, we demonstrate how multidisciplinary national working groups can inform guidelines in real time for bioinformatic quality acceptance criteria. Provision of technical feedback allows laboratory improvement during a pandemic in real time, enhancing public health responses. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. The COVID-19 pandemic has brought the utility of genomics to the forefront of microbial surveillance in public health. Our findings provide recommendations for monitoring bioinformatic quality controls in a pandemic context and how multidisciplinary national working groups can provide technical feedback for actionable improvement towards sequence data concordance.
The evolution and international spread of extensively drug resistant Shigella sonnei
Publisher: Research Square Platform LLC
Date: 15-09-2022
DOI: 10.21203/RS.3.RS-2057516/V1
Abstract: Shigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common and can include resistance to the World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin. Recently, an MSM-associated outbreak of extended-spectrum β-lactamase producing, extensively drug resistant S. sonnei was reported in the United Kingdom. Here, we aimed to identify the genetic basis, natural history, and international dissemination of the outbreak strain. Our genomic epidemiological analyses of 3,304 isolates from the United Kingdom, Australia, Belgium, France, and the United States of America revealed an internationally connected outbreak with a common, low fitness-cost resistance plasmid, previously observed in travel associated sublineages of S. flexneri . Our results highlight the persistent threat of horizontally transmitted antimicrobial resistance and the value of continuing to work towards early and open international sharing of genomic surveillance data.
Increasing antimicrobial resistance in nontyphoidal salmonella isolates in Australia from 1979 to 2015
Publisher: American Society for Microbiology
Date: 02-2018
DOI: 10.1128/AAC.02012-17
Abstract: Australia has high and increasing rates of salmonellosis. To date, the serovar distribution and associated antimicrobial resistance (AMR) patterns of nontyphoidal Salmonella enterica (NTS) in Australia have not been assessed. Such information provides critical knowledge about AMR in the food chain and informs decisions about public health. We reviewed longitudinal data on NTS in two Australian states over a 37-year period, between 1979 and 2015, and antimicrobial resistance since 1984. Overall, 17% of isolates were nonsusceptible to at least one antimicrobial, 4.9% were nonsusceptible to ciprofloxacin, and 0.6% were nonsusceptible to cefotaxime. In total, 2.5% of isolates were from invasive infections, with no significant difference in AMR profiles between invasive and noninvasive isolates. Most isolates with clinically relevant AMR profiles were associated with travel, particularly to Southeast Asia, with multiple “incursions” of virulent and resistant clones into Australia. Our findings represent the largest longitudinal surveillance system for NTS in Australia and provide valuable public health knowledge on the trends and distribution of AMR in NTS. Ongoing surveillance is critical to identify local emergence of resistant isolates.
Impact of Intrapartum Oral Azithromycin on the Acquired Macrolide Resistome of Infants’ Nasopharynx: A Randomized Controlled Trial
Publisher: Oxford University Press (OUP)
Date: 23-05-2020
DOI: 10.1093/CID/CIAA609
Abstract: In a post hoc analysis of s les from an intrapartum azithromycin randomized clinical trial, we found that children whose mothers had been treated with the drug had higher prevalence of macrolide-resistance genes msr(A) and ermC at 28 days but not at 12 months. The 2 genes were positively associated in the nasopharynx. NCT1800942.
Nonrandomized Trial of Weight Loss With Orlistat, Nutrition Education, Diet, and Exercise in Obese Patients With CKD: 2-Year Follow-up
Publisher: Elsevier BV
Date: 2010
DOI: 10.1053/J.AJKD.2009.09.011
Abstract: Obesity increases the comorbidity-adjusted relative risk of developing end-stage renal disease. Body mass index (BMI) > 30 kg/m(2) was a contraindication for transplant in our renal unit until 2008. Open-label prospective nonrandomized intervention. All men and women aged 18-75 years with chronic kidney disease (CKD) and BMI > 30 or > 28 kg/m(2) with diabetes, hypertension, or dyslipidemia and otherwise suitable for kidney transplant if on dialysis therapy were eligible to enroll in the weight-management program. 64 patients were referred 44 agreed to participate in the intervention group and 20 did not wish to take part and constitute the usual-care group. 24-month weight-management program that included a low-fat renal-specific diet, exercise, and orlistat, 120 mg, 3 times daily. Body weight, blood pressure (BP), kidney transplant wait listing. Body weight, BP, estimated glomerular filtration rate (eGFR calculated using the 4-variable Modification of Diet in Renal Disease [MDRD] Study equation). 32 patients (73%) in the weight-management program group completed the follow-up evaluation. Baseline mean BMI was 35.7 +/- 4.5 (SD) kg/m(2) in the weight-management program group and 34.1 +/- 4.2 kg/m(2) in the usual-care group. 12 (38%) patients in the weight-management program and 9 (45%) in usual care had stages 3-4 CKD, with the remainder in stage 5 CKD on dialysis therapy. There were no differences in body weight, BP, or eGFR between groups at baseline. After 24 months, mean body weight was 94.6 +/- 16.1 kg in the weight-management program group versus 101.0 +/- 26.8 kg in the usual-care group (P < 0.001), and eGFR was 43 mL/min in the weight-management program group versus 18 mL/min in the usual-care group (P < 0.001). 9 of 26 (35%) otherwise eligible patients in the weight-management program and 1 of 18 (6%) patients in usual care were accepted for kidney transplant listing, with 3 transplants performed in the weight-management program group and 1 in the usual-care group. Nonrandomized trial, small number of participants. The weight-management program group showed significant weight loss and weight-loss maintenance in obese patients with CKD and potentially enables obese patients with CKD to undergo kidney transplant.
Differences in the population structure of Neisseria meningitidis in two Australian states: Victoria and Western Australia
Publisher: Public Library of Science (PLoS)
Date: 24-10-2017
Evolutionary dynamics of multidrug resistant Salmonella enterica serovar 4,[5],12:i:- in Australia
Publisher: Springer Science and Business Media LLC
Date: 09-08-2021
DOI: 10.1038/S41467-021-25073-W
Abstract: Salmonella enterica serovar 4,[5],12:i:- ( Salmonella 4,[5],12:i:-) is a monophasic variant of Salmonella Typhimurium that has emerged as a global cause of multidrug resistant salmonellosis. We used Bayesian phylodynamics, genomic epidemiology, and phenotypic characterization to describe the emergence and evolution of Salmonella 4,[5],12:i:- in Australia. We show that the interruption of the genetic region surrounding the phase II flagellin, FljB, causing a monophasic phenotype, represents a stepwise evolutionary event through the accumulation of mobile resistance elements with minimal impairment to bacterial fitness. We identify three lineages with different population dynamics and discrete antimicrobial resistance profiles emerged, likely reflecting differential antimicrobial selection pressures. Two lineages are associated with travel to South-East Asia and the third lineage is endemic to Australia. Moreover antimicrobial-resistant Salmonella 4,[5],12:i- lineages efficiently infected and survived in host phagocytes and epithelial cells without eliciting significant cellular cytotoxicity, suggesting a suppression of host immune response that may facilitate the persistence of Salmonella 4,[5],12:i:-.
Microbe-metabolite associations linked to the rebounding murine gut microbiome post-colonization with vancomycin resistant Enterococcus faecium
Publisher: Cold Spring Harbor Laboratory
Date: 21-11-2019
DOI: 10.1101/849539
Abstract: Vancomycin resistant Enterococcus faecium (VREfm) is an emerging antibiotic resistant pathogen. Strain-level investigations are beginning to reveal the molecular mechanisms used by VREfm to colonize regions of the human bowel. However, the role of commensal bacteria during VREfm colonization, in particular following antibiotic treatment, remains largely unknown. We employed licon 16S rRNA gene sequencing and metabolomics in a murine model system to try and investigate functional roles of the gut microbiome during VREfm colonization. First-order taxonomic shifts between Bacteroidetes and Tenerricutes within the gut microbial community composition were detected both in response to pretreatment using ceftriaxone, and to subsequent VREfm challenge. Using neural networking approaches to find co-occurrence profiles of bacteria and metabolites, we detected key metabolome features associated with butyric acid during and after VREfm colonization. These metabolite features were associated with Bacteroides , indicative of a transition towards a pre-antibiotic naïve microbiome. This study shows the impacts of antibiotics on the gut ecosystem, and the progression of the microbiome in response to colonisation with VREfm. Our results offer insights towards identifying potential non-antibiotic alternatives to eliminate VREfm through metabolic re-engineering to preferentially select for Bacteroides . This study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications.
Nutrient Metabolism and Protein-Energy Wasting in Chronic Kidney Disease
Publisher: Elsevier
Date: 2019
Once bitten, twice shy: an unusual case report of a mycotic aortic aneurysm
Publisher: Wiley
Date: 11-2005
DOI: 10.1111/J.1445-2197.2005.03599.X
Abstract: Primary mycotic aneurysms of the aorta are a rare, but potentially lethal condition comprising less than 1% of all aortic aneurysms. All age groups are affected but patients younger than 50 years are most susceptible. Organisms commonly implicated in aortitis and mycotic aortic aneurysms include Salmonella species and Staphylococcus aureus(1). We present the first case report of a primary aortic mycotic aneurysm caused by Capnocytophaga canimorsus, a commensal organism found in the mouth of dogs and cats and occasionally associated with serious human infections.
Case-case-control study on factors associated with vanB vancomycin-resistant and vancomycin-susceptible enterococcal bacteraemia
Publisher: Springer Science and Business Media LLC
Date: 28-06-2014
Abstract: Enterococci are a major cause of healthcare-associated infection. In Australia, vanB vancomycin-resistant enterococci (VRE) is the predominant genotype. There are limited data on the factors linked to vanB VRE bacteraemia. This study aimed to identify factors associated with vanB VRE bacteraemia, and compare them with those for vancomycin-susceptible enterococci (VSE) bacteraemia. A case-case-control study was performed in two tertiary public hospitals in Victoria, Australia. VRE and VSE bacteraemia cases were compared with controls without evidence of enterococcal bacteraemia, but may have had infections due to other pathogens. All VRE isolates had vanB genotype. Factors associated with vanB VRE bacteraemia were urinary catheter use within the last 30 days (OR 2.86, 95% CI 1.09-7.53), an increase in duration of metronidazole therapy (OR 1.65, 95% CI 1.17-2.33), and a higher Chronic Disease Score specific for VRE (OR 1.70, 95% CI 1.05-2.77). Factors linked to VSE bacteraemia were a history of gastrointestinal disease (OR 2.29, 95% CI 1.05-4.99) and an increase in duration of metronidazole therapy (OR 1.23, 95% CI 1.02-1.48). Admission into the haematology/oncology unit was associated with lower odds of VSE bacteraemia (OR 0.08, 95% CI 0.01-0.74). This is the largest case-case-control study involving vanB VRE bacteraemia. Factors associated with the development of vanB VRE bacteraemia were different to those of VSE bacteraemia.
Growth-promoting bacteria double eicosapentaenoic acid yield in microalgae
Publisher: Elsevier BV
Date: 11-2020
A structured weight management programme can achieve improved functional ability and significant weight loss in obese patients with chronic kidney disease
Publisher: Oxford University Press (OUP)
Date: 17-08-2007
DOI: 10.1093/NDT/GFM511
Abstract: Kidney transplantation in obese patients [body mass index (BMI) >30 kg/m(2)] is associated with a poorer outcome, and these patients are therefore often excluded from transplant waiting lists. Conventional weight loss strategies based on a high fibre, low energy diet and exercise are often unsuitable in the chronic kidney disease (CKD) population. A comprehensive multidisciplinary weight management programme comprising a low fat, reduced energy diet, in idual exercise prescription and pharmacotherapy with orlistat 120 mg tds, was initiated to determine whether obese patients with CKD could reach an acceptable weight for transplantation. Thirty-two patients who completed 12 months in the programme were monitored regularly for weight and waist circumference measures as well as exercise performance tests. Twenty-two patients formed a contemporaneous control group. Exercise performance tests included the 6 min timed walk test (6MTWT), sit to stand transfers in 60 s (STS60), timed up and go 3 m (TUAG) and the Duke's activity status index (DASI), a measure of functional ability. Friedman's test analyses were performed to assess differences between baseline and 12-month data. Mean body weight reduced by 7.1% from 102.9 kg to 95.7 kg (P<0.001) This equates to a reduction in BMI from 35.7 kg/m(2) at baseline to 33.2 kg/m(2) at 12 months. Waist circumference decreased by 12.9 cm from 112.9 cm to 100.0 cm (P<0.005) at 12 months. The 6MTWT improved by 45% (P<0.001), STS60 by 30% (P<0.001), TUAG by 37% (P<0.001) and DASI by 50% (P<0.001) after 12 months. To date, two of the patients have received live-related renal transplants and an additional seven patients have now been successfully enrolled onto the transplant waiting list. Preliminary experience from this multidisciplinary programme combining diet, exercise and orlistat suggests that significant weight loss and improved physical functioning can be achieved in obese CKD patients, potentially allowing them the opportunity of kidney transplantation and the associated benefits of this compared with long-term dialysis.
Long-term Impact of Oral Azithromycin Taken by Gambian Women During Labor on Prevalence and Antibiotic Susceptibility of Streptococcus pneumoniae and Staphylococcus aureus in Their Infants: Follow-up
Publisher: Oxford University Press (OUP)
Date: 28-03-2018
DOI: 10.1093/CID/CIY254
AusTrakka: Fast-tracking nationalized genomics surveillance in response to the COVID-19 pandemic
Publisher: Springer Science and Business Media LLC
Date: 14-02-2022
The changing landscape of vancomycin-resistant Enterococcus faecium in Australia: A population-level genomic study
Publisher: Oxford University Press (OUP)
Date: 04-09-2018
DOI: 10.1093/JAC/DKY331
Abstract: Vancomycin-resistant Enterococcus faecium (VREfm) represent a major source of nosocomial infection worldwide. In Australia, there has been a recent concerning increase in bacteraemia associated with the vanA genotype, prompting investigation into the genomic epidemiology of VREfm. A population-level study of VREfm (10 November-9 December 2015) was conducted. A total of 321 VREfm isolates (from 286 patients) across Victoria State were collected and sequenced with Illumina NextSeq. SNPs were used to assess relatedness. STs and genes associated with resistance and virulence were identified. The vanA-harbouring plasmid from an isolate from each ST was assembled using long-read data. Illumina reads from remaining isolates were then mapped to these assemblies to identify their probable vanA-harbouring plasmid. vanA-VREfm comprised 17.8% of isolates. ST203, ST80 and a pstS(-) clade, ST1421, predominated (30.5%, 30.5% and 37.2%, respectively). Most vanB-VREfm were ST796 (77.7%). vanA-VREfm were more closely related within hospitals versus between them [core SNPs 10 (IQR 1-357) versus 356 (179-416), respectively], suggesting discrete introductions of vanA-VREfm, with subsequent intra-hospital transmission. In contrast, vanB-VREfm had similar core SNP distributions within versus between hospitals, due to widespread dissemination of ST796. Different vanA-harbouring plasmids were found across STs. With the exception of ST78 and ST796, Tn1546 transposons also varied. Phylogenetic analysis revealed Australian strains were often interspersed with those from other countries, suggesting ongoing cross-continental transmission. Emerging vanA-VREfm in Australia is polyclonal, indicating repeat introductions of vanA-VREfm into hospitals and subsequent dissemination. The close relationship to global strains reinforces the need for ongoing screening and control of VREfm in Australia and abroad.
Multi-site implementation of whole genome sequencing for hospital infection control: A prospective genomic epidemiological analysis
Publisher: Elsevier BV
Date: 06-2022
Oropharyngeal and Genital Gonorrhea Infections Among Women and Heterosexual Men Reporting Sexual Contact With Partners With Gonorrhea: Implication for Oropharyngeal Testing of Heterosexual Gonorrhea C
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-09-2019
DOI: 10.1097/OLQ.0000000000001068
Abstract: There have been very limited studies of oropharyngeal gonorrhea in heterosexuals. Routine screening of oropharyngeal gonorrhea is not recommended in heterosexual contacts of gonorrhea. This study aimed to examine oropharyngeal gonorrhea positivity among heterosexuals reporting contact with a partner with gonorrhea. At the Melbourne Sexual Health Centre (MSHC), all heterosexual in iduals reporting contact with sexual partners with gonorrhea are tested for genital gonorrhea. In May 2017, MSHC also included screening for oropharyngeal gonorrhea in heterosexual contacts of gonorrhea. All contacts of gonorrhea among women and heterosexual men between May 2017 and November 2018 were reviewed. Site-specific gonorrhea positivity was also calculated. One hundred ninety-one gonorrhea contacts (102 heterosexual men and 89 women) were reviewed. The median age was 28 (interquartile range, 24–33) years. The gonorrhea positivity in males was significantly higher at the oropharynx compared with urethra (18% 95% confidence interval [CI], 11% to 26% vs 2% 95% CI, 0% to 7% P 0.001) and higher at the oropharynx compared with cervicovaginal site in women (46% 95% CI, 35% to 57% vs 36% 95% CI, 26% to 47% P = 0.056). Of the 100 men who did not have genital gonorrhea, 17 (18% 95% CI, 10% to 26%) tested positive at the oropharynx. Of the 55 women who did not have genital gonorrhea, 21 (24% 95% CI, 15% to 34%) tested positive at the oropharynx. Infection at both the oropharynx and genital sites was not associated with sex worker status in women. Overall, 89% and 40% of gonorrhea in heterosexual men and women were only in the oropharynx, respectively. Oropharyngeal gonorrhea testing among heterosexual contacts of gonorrhea may be indicated given a substantial proportion of gonorrhea contacts are only infected at this site.
Does Intragastric Balloon Treatment for Obesity in Chronic Kidney Disease Heighten Acute Kidney Injury Risk?
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000450765
Abstract: b i Background: /i /b The outcomes of intragastric balloon (IGB) placement to achieve weight loss in obese patients with chronic kidney disease (CKD) have not been reported to date. This study aimed to assess the safety and efficacy of the IGB as a weight-loss treatment among this patient population. b i Methods: /i /b A prospective, single-arm, ‘first in CKD' interventional study was conducted in patients with a body mass index kg/m sup /sup and CKD stages 3-4, referred for weight loss. After clinical assessment, the IGB was endoscopically inserted into the stomach and kept in place for 6 months. Complications, adverse events, acceptability, weight loss and metabolic responses were monitored over 6 months. b i Results: /i /b Eleven participants were recruited over 18 months. Two patients withdrew (1 prior to IGB insertion and 1 early removal after 3 days due to persistent vomiting) from the study 9 patients completed the study. There were 5 episodes of acute kidney injury (AKI), occurring in 3 patients. After 6 months, the mean body mass decreased by 9.6% (SD ±6.8). Median waist circumference and total cholesterol decreased significantly (-7.7 cm interquartile range (IQR) -15.3 to -3.9 and -0.2 mmol/l IQR -0.6 to -0.05, respectively), with no changes in estimated glomerular filtration rate, blood pressure, triglycerides, adipokines, inflammation, or arterial stiffness measured by carotid-femoral pulse wave velocity. At IGB removal, there was 1 new case each of gastritis and esophagitis. b i Conclusions: /i /b Treatment with IGB has only moderate efficacy on weight loss yet it results in a high rate of complications in obese patients with established CKD. The risk of AKI may be raised due to increased risk of dehydration secondary to gastrointestinal symptoms associated with IGB placement and reduced baseline kidney function.
Treatment and outcome of 104 hospitalized patients with legionnaires' disease
Publisher: Wiley
Date: 31-10-2003
DOI: 10.1046/J.1445-5994.2003.00422.X
Abstract: Large outbreaks of Legionella pneumonia are rare, but when they occur provide an opportunity to assess predictors of mortality and efficacy of drug therapy. Although erythromycin has been the treatment of choice for many years, newer antimicrobials with increased activity against Legionella are available. A large outbreak of legionnaires' disease associated with the Melbourne Aquarium occurred in April 2000. To describe the patterns and impact of Legionella therapy, and predictors of outcome in a large group of hospitalized patients with legionnaires' disease. A 6-month retrospective audit of hospitalized patients with proven legionnaires' disease around the time of the Melbourne Aquarium outbreak was conducted. Statistical analysis was performed using SAS version 8.0 (SAS Institute Inc., NC, USA). Data were obtained on 104 patients (71 aquarium related, 33 not related). There were six deaths (mortality rate 5.8%), three of which were attributable directly to progressive legionnaires' disease. The major predictors of death were pre-existing cardiac failure (P = 0.0035) and renal disease (P = 0.026). Erythro-mycin is still the most commonly used antibiotic (80% received i.v. erythromycin) with clinicians prescribing more than one active Legionella drug in the majority of cases (76%). Choice of initial antibiotic therapy did not statistically affect outcome as measured by death, length of hospital stay or time to defervescence, although there was a trend towards improved survival with i.v. erythromycin (P = 0.063). Intravenous erythromycin was associated with a 19% rate of phlebitis, whereas side-effects from other antibiotics were uncommon. The most commonly used Legionella therapy in Australia remains erythromycin. This continues to be an effective agent, however, side-effects are common.
Genomics-informed responses in the elimination of COVID-19 in Victoria, Australia: an observational, genomic epidemiological study
Publisher: Elsevier BV
Date: 08-2021
Clinical manifestations and outcome in HIV‐infected young infants presenting with acute illness in Durban, South Africa
Publisher: Informa UK Limited
Date: 02-2011
Emergence and global spread of Listeria monocytogenes main clinical clonal complex
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-12-2021
Abstract: Analyses of ~2000 genomes of Listeria monocytogenes main clinical clone reveal its global spread and dynamics.
Evaluation of Serological Tests for SARS-CoV-2: Implications for Serology Testing in a Low-Prevalence Setting
Publisher: Oxford University Press (OUP)
Date: 06-08-2020
Abstract: Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little premarket validation. Performance characteristics for 5 PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralization test (sVNT). Sensitivities for PoCT ranged from 51.8% (95% confidence interval [CI], 43.1%–60.4%) to 67.9% (95% CI, 59.4%–75.6%), and specificities from 95.6% (95% CI, 89.2%–98.8%) to 100.0% (95% CI, 96.1%–100.0%). ELISA sensitivity for IgA or IgG detection was 67.9% (95% CI, 59.4%–75.6%), increasing to 93.8% (95% CI, 85.0%–98.3%) for s les & days post symptom onset. sVNT sensitivity was 60.9% (95% CI, 53.2%–68.4%), rising to 91.2% (95% CI, 81.8%–96.7%) for s les & days post symptom onset, with specificity 94.4% (95% CI, 89.2%–97.5%). Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.
Treating Gram-positive infections: vancomycin update and the whys, wherefores and evidence base for continuous infusion of anti-Gram-positive antibiotics
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2009
Comprehensive Genomic Investigation of Adaptive Mutations Driving the Low-Level Oxacillin Resistance Phenotype in Staphylococcus aureus.
Publisher: American Society for Microbiology
Date: 22-12-2020
Abstract: The majority of Staphylococcus aureus strains causing human disease are methicillin-susceptible (MSSA) and can be treated with antistaphylococcal penicillins (such as oxacillin). While acquisition of the mec gene represents the main resistance mechanism to oxacillin, S. aureus can acquire low-level resistance through adaptive mutations in other genes. In this study, we used genomic approaches to understand the basis of S. aureus adaption to oxacillin and its dynamic at the population level. By combining a genome analysis of clinical isolates from persistent MSSA infections, in vitro selection of oxacillin resistance, and genome-wide association analysis on a large collection of isolates, we identified 21 genes linked to secondary oxacillin resistance. Adaptive mutations in these genes were easy to select when S. aureus was exposed to oxacillin, but they also came at a substantial cost in terms of bacterial fitness, suggesting that this phenotype emerges preferentially in the setting of sustained antibiotic exposure.
Molecular Epidemiology of Enterococcal Bacteremia in Australia
Publisher: American Society for Microbiology
Date: 03-2014
DOI: 10.1128/JCM.03286-13
Abstract: Enterococci are a major cause of health care-associated infections and account for approximately 10% of all bacteremias globally. The aim of this study was to determine the proportion of enterococcal bacteremia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to icillin and the glycopeptides, and to characterize the molecular epidemiology of the Enterococcus faecalis and Enterococcus faecium isolates. From 1 January to 31 December 2011, 1,079 unique episodes of bacteremia were investigated, of which 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). The majority of bacteremias were health care associated, and approximately one-third were polymicrobial. Ampicillin resistance was detected in 90.4% of E. faecium isolates but was not detected in E. faecalis isolates. Vancomycin nonsusceptibility was reported in 0.6% and 36.5% of E. faecalis and E. faecium isolates, respectively. Unlike Europe and the United States, where vancomycin resistance in E. faecium is predominately due to the acquisition of the vanA operon, 98.4% of E. faecium isolates harboring van genes carried the vanB operon, and 16.1% of the vanB E. faecium isolates had vancomycin MICs at or below the susceptible breakpoint of the CLSI. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis pulsotypes, % belonged to two pulsotypes that were isolated across Australia. E. faecium consisted of 73 pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium isolates were identified as CC17 clones, of which approximately half were characterized as ST203, which was isolated Australia-wide. In conclusion, the Australian Enterococcal Sepsis Outcome Programme (AESOP) study has shown that although they are polyclonal, enterococcal bacteremias in Australia are frequently caused by icillin-resistant vanB E. faecium .
Vancomycin in the treatment of methicillin-resistant Staphylococcus aureus – a clinician’s guide to the science informing current practice
Publisher: Informa UK Limited
Date: 06-05-2015
DOI: 10.1586/14787210.2015.1041924
Abstract: Clinicians treating an infection assess a patient in terms of disease manifestation, causative organism and available antibiotic options with the aim of devising a therapeutic strategy under the creed of 'first, do no harm'. It is often only when treatment is failing or options are limited, as in the scenario of multidrug-resistant organisms, that consideration is given to the interplay that occurs between the microbe and the host. The emergence of Staphylococcus aureus with reduced susceptibility to vancomycin provides a prime ex le of these dynamic interactions. This review shall explore these concepts in relation to vancomycin for the treatment of methicillin-resistant S. aureus, with the aim of providing an informed approach to the utilization of this drug.
Comparative genomics shows that Mycobacterium ulcerans migration and expansion preceded the rise of Buruli ulcer in southeastern Australia
Publisher: American Society for Microbiology
Date: 15-04-2018
DOI: 10.1128/AEM.02612-17
Abstract: Since 2000, cases of the neglected tropical disease Buruli ulcer, caused by infection with Mycobacterium ulcerans , have increased 100-fold around Melbourne (population 4.4 million), the capital of Victoria, in temperate southeastern Australia. The reasons for this increase are unclear. Here, we used whole-genome sequence comparisons of 178 M. ulcerans isolates obtained primarily from human clinical specimens, spanning 70 years, to model the population dynamics of this pathogen from this region. Using phylogeographic and advanced Bayesian phylogenetic approaches, we found that there has been a migration of the pathogen from the east end of the state, beginning in the 1980s, 300 km west to the major human population center around Melbourne. This move was then followed by a significant increase in M. ulcerans population size. These analyses inform our thinking around Buruli ulcer transmission and control, indicating that M. ulcerans is introduced to a new environment and then expands, rather than it being from the awakening of a quiescent pathogen reservoir. IMPORTANCE Buruli ulcer is a destructive skin and soft tissue infection caused by Mycobacterium ulcerans and is characterized by progressive skin ulceration, which can lead to permanent disfigurement and long-term disability. Despite the majority of disease burden occurring in regions of West and central Africa, Buruli ulcer is also becoming increasingly common in southeastern Australia. Major impediments to controlling disease spread are incomplete understandings of the environmental reservoirs and modes of transmission of M. ulcerans . The significance of our research is that we used genomics to assess the population structure of this pathogen at the Australian continental scale. We have then reconstructed a historical bacterial spread and modeled demographic dynamics to reveal bacterial population expansion across southeastern Australia. These findings provide explanations for the observed epidemiological trends with Buruli ulcer and suggest possible management to control disease spread.
Decreased Copper in Alzheimer’s Disease Brain Is Predominantly in the Soluble Extractable Fraction
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/623241
Abstract: Alzheimer’s disease (AD) is the leading cause of dementia and represents a significant burden on the global economy and society. The role of transition metals, in particular copper (Cu), in AD has become of significant interest due to the dyshomeostasis of these essential elements, which can impart profound effects on cell viability and neuronal function. We tested the hypothesis that there is a systemic perturbation in Cu compartmentalization in AD, within the brain as well as in the periphery, specifically within erythrocytes. Our results showed that the previously reported decrease in Cu within the human frontal cortex was confined to the soluble ( P 0.05 ) and total homogenate ( P 0.05 ) fractions. No differences were observed in Cu concentration in erythrocytes. Our data indicate that there is a brain specific alteration in Cu levels in AD localized to the soluble extracted material, which is not reflected in erythrocytes. Further studies using metalloproteomics approaches will be able to elucidate the metabolic mechanism(s) that results in the decreased brain Cu levels during the progression of AD.
Genomic epidemiology offers high resolution estimates of serial intervals for COVID-19
Publisher: Cold Spring Harbor Laboratory
Date: 03-03-2022
DOI: 10.1101/2022.02.23.22271355
Abstract: Estimating key aspects of transmission is crucial in infectious disease control. Serial intervals – the time between symptom onset in an infector and infectee – are fundamental, and help to define rates of transmission, estimates of reproductive numbers, and vaccination levels needed to prevent transmission. However, estimating the serial interval requires knowledge of in iduals’ contacts and exposures (who infected whom), which is typically obtained through resource-intensive contact tracing efforts. We develop an alternate framework that uses virus sequences to inform who infected whom and thereby estimate serial intervals. The advantages are many-fold: virus sequences are often routinely collected to support epidemiological investigations and to monitor viral evolution. The genomic approach offers high resolution and cluster-specific estimates of the serial interval that are comparable with those obtained from contact tracing data. Our approach does not require contact tracing data, and can be used in large populations and over a range of time periods. We apply our techniques to SARS-CoV-2 sequence data from the first two waves of COVID-19 in Victoria, Australia. We find that serial interval estimates vary between clusters, supporting the need to monitor this key parameter and use updated estimates in onward applications. Compared to an early published serial interval estimate, using cluster-specific serial intervals can cause estimates of the effective reproduction number R t to vary by a factor of up to 2–3. We also find that serial intervals estimated in settings such as schools and meat processing acking plants tend to be shorter than those estimated in healthcare facilities.
Isolates with low-level vancomycin resistance associated with persistent methicillin-resistant Staphylococcus aureus bacteremia
Publisher: American Society for Microbiology
Date: 09-2006
DOI: 10.1128/AAC.00422-06
Abstract: Low-level vancomycin-resistant Staphylococcus aureus (vancomycin-intermediate S. aureus [VISA] and heterogenous VISA [hVISA]) is increasingly reported and leads to glycopeptide treatment failure. Various phenotypic features have been reported for these isolates, but the genetic changes leading to hVISA and VISA have yet to be clearly determined. We assessed phenotypic, antibiotic resistance, and genomic changes by using genomic DNA microarray comparison and sequencing of selected loci in five pairs of clinical hVISA/VISA strains and the initial methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained prior to vancomycin therapy. The isolates were from adult patients in Australia and New Zealand who had persistent MRSA bacteremia ( days) while receiving vancomycin therapy. In all cases, the initial isolates were found to be fully vancomycin-susceptible Staphylococcus aureus (VSSA). The hVISA/VISA phenotype was associated with increased cell wall thickness, reduced autolytic activity in four of five hVISA/VISA strains, and a striking reduction in biofilm formation compared to the parent strains in all pairs. All five pairs appeared to be isogenic, and genomic DNA microarray comparison suggested that major genetic changes are not required for the development of the resistant phenotype in these strains. No sequence differences were found in the agr locus or the tcaRA genes for any pair, but a marked reduction in RNAIII expression was found in four pairs. In summary, hVISA/VISA arises from fully VSSA during persistent infection that fails to respond to glycopeptide therapy and is associated with significant phenotypic changes, including a marked reduction in biofilm-forming ability. These clinically derived pairs of isolates will be a useful resource to elucidate the genetic mechanism of resistance in hVISA/VISA strains.
Creatinine index: a retrospective cohort study in an urban Australian dialysis context
Publisher: Wiley
Date: 31-03-2023
DOI: 10.1111/IMJ.16054
Abstract: This study aimed to described the relationship between the CI and mortality in an Australian context. Maintenance haemodialysis is a catabolic state associated with a significant decrease in lean body mass (LBM) and protein energy wasting. LBM can be derived or estimated from creatinine kinetic modelling, specifically the creatinine index (CI). This has been demonstrated in cohort studies to predict mortality. One hundred seventy‐nine patients undergoing haemodialysis in 2015 were included in this cohort. They were followed for 5 years with pertinent clinical data collected to calculate the CI as of December 2015. For analysis, patients were split into a high and low CI group based on the median (18.32 mg/kg/day). The primary outcome of interest was all‐cause mortality, and secondary outcomes included myocardial infarction, stroke and transplantation. During follow‐up, 69 (76.7%) patients in the low CI group and 28 (31.5%) patients in the high CI group died ( P 0.001). The relative risk (RR) of mortality within the low compared with the high CI group was 2.43 (95% confidence interval, 1.75–3.38). Fully adjusted Cox proportional hazards modelling demonstrated a hazard ratio (HR) of 0.498 (95% CI, 0.292–0.848) for survival in the high CI group. Lower CI was associated with increased risk of stroke (RR, 5.43 [95% CI, 1.24–23.84]), whereas transplant was more likely in the high CI group (RR, 6.4 [95% confidence interval, 1.96–20.88]). In a single‐centre Australian haemodialysis cohort, the CI was strongly associated with mortality and stroke risk. The CI is an accurate and simple method to identify patients with low LBM at risk for significant morbidity and mortality.
Multi-site assessment of rapid, point-of-care antigen testing for the diagnosis of SARS-CoV-2 infection in a low-prevalence setting: A validation and implementation study
Publisher: Elsevier BV
Date: 04-2021
Failure of Vancomycin for Treatment of Methicillin-Resistant Staphylococcus aureus Infections
Publisher: Oxford University Press (OUP)
Date: 15-11-2004
DOI: 10.1086/425129
Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates
Publisher: American Society for Microbiology
Date: 09-2014
DOI: 10.1128/JCM.01320-14
Abstract: An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator ( agr ) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [ P 0.001]) or low (CC22 [ P 0.001], CC88 [ P 0.001], and CC188 [ P = 0.002]) vancomycin MIC. agr dysfunction ( P = 0.014) or agr genotype II ( P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ ( P = 0.002), sea ( P 0.001), clfA ( P 0.001), splA ( P = 0.001), and the arginine catabolic mobile element (ACME) locus ( P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes.
Genomic investigation of the emergence of vanD vancomycin resistant Enterococcus faecium
Publisher: Microbiology Society
Date: 04-10-2023
Body mass index and chronic kidney disease outcomes after acute kidney injury: a prospective matched cohort study
Publisher: Springer Science and Business Media LLC
Date: 28-05-2021
DOI: 10.1186/S12882-021-02400-3
Abstract: Acute kidney injury (AKI) and obesity are independent risk factors for chronic kidney disease (CKD). This study aimed to determine if obesity modifies risk for CKD outcomes after AKI. This prospective multisite cohort study followed adult survivors after hospitalization, with or without AKI. The primary outcome was a combined CKD event of incident CKD, progression of CKD and kidney failure, examined using time-to-event Cox proportional hazards models, adjusted for diabetes status, age, pre-existing CKD, cardiovascular disease status and intensive care unit admission, and stratified by study center. Body mass index (BMI) was added as an interaction term to examine effect modification by body size. The cohort included 769 participants with AKI and 769 matched controls. After median follow-up of 4.3 years, among AKI survivors, the rate of the combined CKD outcome was 84.7 per1000-person-years with BMI ≥30 kg/m 2 , 56.4 per 1000-person-years with BMI 25–29.9 kg/m 2 , and 72.6 per 1000-person-years with BMI 20–24.9 kg/m 2 . AKI was associated with a higher risk of combined CKD outcomes adjusted-HR 2.43 (95%CI 1.87–3.16), with no evidence that this was modified by BMI ( p for interaction = 0.3). After adjustment for competing risk of death, AKI remained associated with a higher risk of the combined CKD outcome (subdistribution-HR 2.27, 95%CI 1.76–2.92) and similarly, there was no detectable effect of BMI modifying this risk. In this post-hospitalization cohort, we found no evidence for obesity modifying the association between AKI and development or progression of CKD.
Fulminant meningococcal sepsis due to non-groupable Neisseria meningitidis in a patient receiving eculizumab
Publisher: AMPCo
Date: 06-2018
DOI: 10.5694/MJA17.01012
Improved Outcomes with Linezolid for Methicillin-Resistant Staphylococcus aureus Infections: Better Drug or Reduced Vancomycin Susceptibility?
Publisher: American Society for Microbiology
Date: 11-2005
Correspondence: Spontaneous secondary mutations confound analysis of the essential two-component system WalKR in Staphylococcus aureus
Publisher: Springer Science and Business Media LLC
Date: 06-02-2017
DOI: 10.1038/NCOMMS14403
Optimising genomic approaches for identifying vancomycin-resistant Enterococcus faecium transmission in healthcare settings
Publisher: Springer Science and Business Media LLC
Date: 26-01-2022
DOI: 10.1038/S41467-022-28156-4
Abstract: Vancomycin-resistant Enterococcus faecium (VREfm) is a major nosocomial pathogen. Identifying VREfm transmission dynamics permits targeted interventions, and while genomics is increasingly being utilised, methods are not yet standardised or optimised for accuracy. We aimed to develop a standardized genomic method for identifying putative VREfm transmission links. Using comprehensive genomic and epidemiological data from a cohort of 308 VREfm infection or colonization cases, we compared multiple approaches for quantifying genetic relatedness. We showed that clustering by core genome multilocus sequence type (cgMLST) was more informative of population structure than traditional MLST. Pairwise genome comparisons using split k-mer analysis (SKA) provided the high-level resolution needed to infer patient-to-patient transmission. The more common mapping to a reference genome was not sufficiently discriminatory, defining more than three times more genomic transmission events than SKA (3729 compared to 1079 events). Here, we show a standardized genomic framework for inferring VREfm transmission that can be the basis for global deployment of VREfm genomics into routine outbreak detection and investigation.
Analysis of the Small RNA Transcriptional Response in Multidrug-Resistant Staphylococcus aureus after Antimicrobial Exposure
Publisher: American Society for Microbiology
Date: 08-2013
DOI: 10.1128/AAC.00263-13
Abstract: The critical role of noncoding small RNAs (sRNAs) in the bacterial response to changing conditions is increasingly recognized. However, a specific role for sRNAs during antibiotic exposure has not been investigated in Staphylococcus aureus . Here, we used Illumina RNA-Seq to examine the sRNA response of multiresistant sequence type 239 (ST239) S. aureus after exposure to four antibiotics (vancomycin, linezolid, ceftobiprole, and tigecycline) representing the major classes of antimicrobials used to treat methicillin-resistant S. aureus (MRSA) infections. We identified 409 potential sRNAs and then compared global sRNA and mRNA expression profiles at 2 and 6 h, without antibiotic exposure and after exposure to each antibiotic, for a vancomycin-susceptible strain (JKD6009) and a vancomycin-intermediate strain (JKD6008). Exploration of this data set by multivariate analysis using a novel implementation of nonnegative matrix factorization (NMF) revealed very different responses for mRNA and sRNA. Where mRNA responses clustered with strain or growth phase conditions, the sRNA responses were predominantly linked to antibiotic exposure, including sRNA responses that were specific for particular antibiotics. A remarkable feature of the antimicrobial response was the prominence of antisense sRNAs to genes encoding proteins involved in protein synthesis and ribosomal function. This study has defined a large sRNA repertoire in epidemic ST239 MRSA and shown for the first time that a subset of sRNAs are part of a coordinated transcriptional response to specific antimicrobial exposures in S. aureus . These data provide a framework for interrogating the role of staphylococcal sRNAs in antimicrobial resistance and exploring new avenues for sRNA-based antimicrobial therapies.
Bilateral osteomyelitis and liver abscess caused by hypervirulent Klebsiella pneumoniae- a rare clinical manifestation
Publisher: Springer Science and Business Media LLC
Date: 07-08-2018
Coxiella burnetii endocarditis after Q fever vaccination
Publisher: Microbiology Society
Date: 12-2012
Abstract: Coxiella burnetii is the causative bacterium of Q fever, a vaccine-preventable infection. C. burnetii is an unusual cause of culture-negative endocarditis. Here, we present a case of Q fever native valve endocarditis that developed in a young man despite prior vaccination. Definitive diagnosis was difficult and required C. burnetii-specific PCR testing.
Staphylococcus aureus host interactions and adaptation
Publisher: Springer Science and Business Media LLC
Date: 27-01-2023
The changing landscape of VREfm in Victoria, Australia: A State-wide genomic snapshot
Publisher: Cold Spring Harbor Laboratory
Date: 28-03-2018
DOI: 10.1101/289975
Abstract: Vancomycin-resistant Enterococcus faecium (VREfm) represent a major source of nosocomial infection worldwide. In Australia, the vanB genotype is dominant however there has been a recent increase in the predominantly plasmid-encoded vanA genotype, prompting investigation into the genomic epidemiology of VREfm in this context. A cross-sectional study of VREfm in Victoria, Australia (Nov.10 th - Dec.9 th , 2015). A total of 321 VREfm isolates (from 286 patients) were collected and whole-genome sequenced with Illumina NextSeq. Single nucleotide polymorphisms (SNPs) were used to assess relatedness. Multi-locus sequence types (STs), and genes associated with resistance and virulence were identified. The vanA -harbouring plasmid from an isolate from each ST was assembled using long-read data. vanA -VREfm comprised 17.8% of isolates. ST203, ST80 and a pstS (-) clade, ST1421, predominated (30.5%, 30.5% and 37.2% of vanA -VREfm, respectively). Most vanB- VREfm were ST796 (77.7%). vanA -VREfm isolates were closely-related within hospitals vs. between them (core SNPs 10 [interquartile range 1-357] vs. 356 [179-416] respectively), suggesting discrete introductions of vanA -VREfm, with subsequent intra-hospital transmission. In contrast, vanB -VREfm had similar core SNP distributions within vs. between hospitals, due to widespread dissemination of ST796. Overall, vanA -harbouring plasmids differed across STs, and with exception of ST78 and ST796, Tn 1546 transposons also varied. vanA -VREfm in Victoria is associated with multiple STs, and is not solely mediated by a single shared plasmid/Tn 1546 transposon clonal transmission appears to play an important role, predominantly within, rather than between, hospitals. In contrast, vanB- VREfm appears to be well-established and widespread across Victorian healthcare institutions.
The growing burden of multidrug-resistant infections among returned Australian travellers
Publisher: AMPCo
Date: 02-2014
DOI: 10.5694/MJA13.10592
Evolution of virulence in Enterococcus faecium, a hospital-adapted opportunistic pathogen
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.MIB.2017.11.030
Abstract: Enterococci are long-standing members of the human microbiome and they are also widely distributed in nature. However, with the surge of antibiotic-resistance in recent decades, two enterococcal species (Enterococcus faecalis and Enterococcus faecium) have emerged to become significant nosocomial pathogens, acquiring extensive antibiotic resistance. In this review, we summarize what is known about the evolution of virulence in E. faecium, highlighting a specific clone of E. faecium called ST796 that has emerged recently and spread globally.
Reflex Detection of Ciprofloxacin Resistance in Neisseria gonorrhoeae by Use of the SpeeDx ResistancePlus GC Assay
Publisher: American Society for Microbiology
Date: 20-04-2021
DOI: 10.1128/JCM.00089-21
Abstract: Resistance-guided therapy (RGT) for gonorrhoea may reduce unnecessary use of broad-spectrum antibiotics. When reflexed from the Aptima Combo 2 assay, the ResistancePlus GC assay demonstrated 94.8% sensitivity and 100.0% specificity for Neisseria gonorrhoeae detection.
Bacterial Load of Chlamydia trachomatis in the Posterior Oropharynx, Tonsillar Fossae, and Saliva among Men Who Have Sex with Men with Untreated Oropharyngeal Chlamydia
Publisher: American Society for Microbiology
Date: 23-12-2020
DOI: 10.1128/JCM.01375-19
Abstract: The aim of this study was to determine whether Chlamydia trachomatis could be detected in saliva and if infection is specific to an anatomical site in the oropharynx. Men who have sex with men (MSM) who were diagnosed with oropharyngeal chlamydia at the Melbourne Sexual Health Centre in 2017-2018 were invited to participate upon returning for treatment. Swabs at the tonsillar fossae and posterior oropharynx and a saliva s le were collected.
Condition dependence of phenotypic integration and the evolvability of genitalic traits in a neriid fly
Publisher: The Royal Society
Date: 05-2020
Abstract: The spectacular ersity of insect male genitalia, and their relative insensitivity to the environment, have long puzzled evolutionary biologists and taxonomists. We asked whether the unusual evolvability of male genitalia could be associated with low morphological integration of genitalic traits, by comparison with male somatic traits and female traits. We also asked whether this pattern was robust to variation in resource availability during development, which affects adult condition. To address these questions, we manipulated larval diet quality in a split-brood design and compared levels of integration of male and female genitalic and somatic traits in the neriid fly, Telostylinus angusticollis . We found that male genitalic traits were substantially less integrated than male somatic traits, and less integrated than female genitalic traits. Female genitalic traits were also less integrated than female somatic traits, but the difference was less pronounced than in males. However, integration of male genitalic traits was negatively condition-dependent, with high-condition males exhibiting lower trait integration than low-condition males. Finally, genitalic traits exhibited lower larval diet × family interactions than somatic traits. These results could help explain the unusually high evolvability of male genitalic traits in insects.
Hidden Resistances: How Routine Whole-Genome Sequencing Uncovered an Otherwise Undetected blaNDM-1 Gene in Vibrio alginolyticus from Imported Seafood.
Publisher: American Society for Microbiology
Date: 14-02-2023
DOI: 10.1128/SPECTRUM.04176-22
Abstract: Carbapenems are last-line antimicrobials, vital for use in human medicine. Antimicrobial resistance determinants such as bla NDM (New Delhi metallo-β-lactamase producing) genes conferring resistance to the carbapenem class of antimicrobials, are typically found in Enterobacterales (first described in 2009 from a Klebsiella pneumoniae isolate).
The global dissemination of hospital clones of Enterococcus faecium
Publisher: Springer Science and Business Media LLC
Date: 30-03-2021
DOI: 10.1186/S13073-021-00868-0
Abstract: The hospital-adapted A1 group of Enterococcus faecium remains an organism of significant concern in the context of drug-resistant hospital-associated infections. How this pathogen evolves and disseminates remains poorly understood. A large, globally representative collection of short-read genomic data from the hospital-associated A1 group of Enterococcus faecium was assembled ( n = 973). We analysed, using a novel analysis approach, global ersity in terms of both the dynamics of the accessory genome and homologous recombination among conserved genes. Two main modes of genomic evolution continue to shape E. faecium : the acquisition and loss of genes, including antimicrobial resistance genes, through mobile genetic elements including plasmids, and homologous recombination of the core genome. These events lead to new clones emerging at the local level, followed by the erosion of signals of clonality through recombination, and in some identifiable cases producing new clonal clusters. These patterns lead to new, emerging lineages which are able to spread globally over relatively short timeframes. The ability of A1 E. faecium to continually present new combinations of genes for potential selection suggests that controlling this pathogen will remain challenging but establishing a framework for understanding genomic evolution is likely to aid in tracking the threats posed by newly emerging lineages.
Genomic Epidemiology and Antimicrobial Resistance Mechanisms of Imported Typhoid in Australia
Publisher: American Society for Microbiology
Date: 17-11-2021
DOI: 10.1128/AAC.01200-21
Abstract: Typhoid fever is an invasive bacterial disease of humans that disproportionately affects low- and middle-income countries. Antimicrobial resistance (AMR) has been increasingly prevalent in recent decades in Salmonella enterica serovar Typhi ( S.
Decreased vancomycin susceptibility in Staphylococcus aureus caused by IS256 tempering of walKR expression
Publisher: American Society for Microbiology
Date: 07-2013
DOI: 10.1128/AAC.00279-13
Abstract: Vancomycin-intermediate Staphylococcus aureus (VISA) strains often arise by mutations in the essential two-component regulator walKR however their impact on walKR function has not been definitively established. Here, we investigated 10 MRSA strains recovered serially after exposure of vancomycin-susceptible S. aureus (VSSA) JKD6009 to simulated human vancomycin dosing regimens (500 mg to 4,000 mg every 12 h) using a 10-day hollow fiber infection model. After continued exposure to the vancomycin regimens, two isolates displayed reduced susceptibility to both vancomycin and daptomycin, developing independent IS 256 insertions in the walKR 5′ untranslated region (5′ UTR). Quantitative reverse transcription-PCR (RT-PCR) revealed a 50% reduction in walKR gene expression in the IS 256 mutants compared to the VSSA parent. Green fluorescent protein (GFP) reporter analysis, promoter mapping, and site-directed mutagenesis confirmed these findings and showed that the IS 256 insertions had replaced two SigA-like walKR promoters with weaker, hybrid promoters. Removal of IS 256 reverted the phenotype to VSSA, showing that reduced expression of WalKR did induce the VISA phenotype. Analysis of selected WalKR-regulated autolysins revealed upregulation of ssaA but no change in expression of sak and sceD in both IS 256 mutants. Whole-genome sequencing of the two mutants revealed an additional IS 256 insertion within agrC for one mutant, and we confirmed that this mutation abolished agr function. These data provide the first substantial analysis of walKR promoter function and show that prolonged vancomycin exposure can result in VISA through an IS 256 -mediated reduction in walKR expression however, the mechanisms by which this occurs remain to be determined.
Comprehensive antibiotic-linked mutation assessment by Resistance Mutation Sequencing (RM-seq)
Publisher: Cold Spring Harbor Laboratory
Date: 31-01-2018
DOI: 10.1101/257915
Abstract: Acquired mutations are a major mechanism of bacterial antibiotic resistance generation and dissemination, and can arise during treatment of infections. Early detection of sub-populations of resistant bacteria harbouring defined resistance mutations could prevent inappropriate antibiotic prescription. Here we present RM-seq, a new licon-based DNA sequencing workflow based on single molecule barcoding coupled with deep-sequencing that enables the high-throughput characterisation and sensitive detection of resistance mutations from complex mixed populations of bacteria. We show that RM-seq reduces both background sequencing noise and PCR lification bias and allows highly sensitive identification and accurate quantification of antibiotic resistant sub-populations, with relative allele frequencies as low as 10 -4 . We applied RM-seq to identify and quantify rif icin resistance mutations in Staphylococcus aureus using pools of 10,000 in vitro selected clones and identified a large number of previously unknown resistance-associated mutations. Targeted mutagenesis and phenotypic resistance testing was used to validate the technique and demonstrate that RM-seq can be used to link subsets of mutations with clinical resistance breakpoints at high-throughput using large pools of in vitro selected resistant clones. Differential analysis of the abundance of resistance mutations after a selection bottleneck detected antimicrobial cross-resistance and collateral sensitivity-conferring mutations. Using a mouse infection model and human clinical s les, we also demonstrate that RM-seq can be effectively applied in vivo to track complex mixed populations of S. aureus and another major human pathogen, Mycobacterium tuberculosis during infections. RM-seq is a powerful new tool to both detect and functionally characterise mutational antibiotic resistance.
CAMERA2 - combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection: Study protocol for a randomised controlled trial
Publisher: Springer Science and Business Media LLC
Date: 31-03-2016
Niche-specific genome degradation and convergent evolution shaping Staphylococcus aureus adaptation during severe infections
Publisher: Cold Spring Harbor Laboratory
Date: 12-02-2022
DOI: 10.1101/2022.02.11.480068
Abstract: During severe infections, Staphylococcus aureus moves from its colonising sites to blood and tissues, and is exposed to new selective pressures, thus potentially driving adaptive evolution. Previous studies have shown the key role of the agr locus in S. aureus pathoadaptation, however a more comprehensive characterisation of genetic signatures of bacterial adaptation may enable prediction of clinical outcomes and reveal new targets for treatment and prevention of these infections. Here, we measured adaptation using within-host evolution analysis of 2,590 S. aureus genomes from 396 independent episodes of infection. By capturing a comprehensive repertoire of single-nucleotide and structural genome variations, we found evidence of a distinctive evolutionary pattern within the infecting populations compared to colonising bacteria. These invasive strains had up to 20-fold enrichments for genome degradation signatures and displayed significantly convergent mutations in a distinctive set of genes, linked to antibiotic response and pathogenesis. In addition to agr -mediated adaptation we identified non-canonical, genome-wide significant loci including sucA - sucB and stp1 . The prevalence of adaptive changes increased with infection extent, emphasising the clinical significance of these signatures. These findings provide a high-resolution picture of the molecular changes when S. aureus transitions from colonisation to severe infection and may inform correlation of infection outcomes with adaptation signatures.
Evaluation of serological tests for SARS-CoV-2: Implications for serology testing in a low-prevalence setting
Publisher: Cold Spring Harbor Laboratory
Date: 03-06-2020
DOI: 10.1101/2020.05.31.20118273
Abstract: Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little pre-market validation. Performance characteristics for five PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralisation test (sVNT). Sensitivities for PoCT ranged from 51.8% (95% CI 43.1 to 60.4%) to 67.9% (95% CI 59.4–75.6%), and specificities from 95.6% (95% CI 89.2–98.8%) to 100.0% (95% CI 96.1–100.0%). Overall ELISA sensitivity for either IgA or IgG detection was 67.9% (95% CI 59.4–75.6), increasing to 93.8% (95% CI 85.0–98.3%) for s les 14 days post symptom onset. Overall, sVNT sensitivity was 60.9% (95% CI 53.2–68.4%), rising to 91.2%% (95% CI 81.8–96.7%) for s les collected 14 days post-symptom onset, with a specificity 94.4% (95% CI 89.2–97.5%), Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in the reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.
Standardised Outcome Reporting for the Nutrition Management of Complex Chronic Disease: A Rapid Review
Publisher: MDPI AG
Date: 26-09-2021
DOI: 10.3390/NU13103388
Abstract: In iduals with coexisting chronic diseases or with complex chronic disease are among the most challenging and costly patients to treat, placing a growing demand on healthcare systems. Recommending effective treatments, including nutrition interventions, relies on standardised outcome reporting from randomised controlled trials (RCTs) to enable data synthesis. This rapid review sought to determine how the scope and consistency of the outcomes reported by RCTs investigating nutrition interventions for the management of complex chronic disease compared to what is recommended by the core outcome sets (COS) for in idual disease states. Peer-reviewed RCTs published between January 2010 and July 2020 were systematically sourced from PubMed, CINAHL and Embase, and COS were sourced from the International Consortium for Health Outcomes Measurements (ICHOM) and the Core Outcome Measures in Effectiveness Trials (COMET) database. A total of 45 RCTs (43 studies) and 7 COS were identified. Outcomes were extracted from both the RCTs and COS and were organised using COMET Taxonomy Core Areas. A total of 66 outcomes and 439 outcome measures were reported by the RCTs. The RCTs demonstrated extensive outcome heterogeneity, with only five outcomes (5/66, 8%) being reported with relative consistency (cited by ≥50% of publications). Furthermore, the scope of the outcomes reported by studies was limited, with a notable paucity of patient-reported outcomes. Poor agreement (25%) was observed between the outcomes reported in the RCTs and those recommended by the COS. This review urges greater uptake of the existing COS and the development of a COS for complex chronic disease to be considered so that evidence can be better synthesised regarding effective nutrition interventions.
Health Outcomes from Multidrug-Resistant Salmonella Infections in High-Income Countries: A Systematic Review and Meta-Analysis
Publisher: Mary Ann Liebert Inc
Date: 07-2018
Abstract: Salmonella is a leading cause of foodborne enterocolitis worldwide. Antimicrobial use in food animals is the driving force for antimicrobial resistance among Salmonella particularly in high-income countries. Nontyphoidal Salmonella (NTS) infections that are multidrug resistant (MDR) (nonsusceptible to ≥1 agent in ≥3 antimicrobial categories) may result in more severe health outcomes, although these effects have not been systematically examined. We conducted a systematic review and meta-analysis to examine impacts of MDR NTS on disease outcomes in high-income settings. We systematically reviewed the literature from scientific databases, including PubMed, Scopus, and grey literature sources, using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. We included peer-reviewed publications of case-control and cohort studies, outbreak investigations, and published theses, imposing no language restriction. We included publications from January 1, 1990 through September 15, 2016 from high-income countries as classified by the World Bank, and extracted data on duration of illness, hospitalization, morbidity and mortality of MDR, and pan-susceptible NTS infections. After removing duplicates, the initial search revealed 4258 articles. After further screening, 16 eligible studies were identified for the systematic review, but, only 9 of these were included in the meta-analysis. NTS serotypes differed among the reported studies, but serotypes Typhimurium, Enteritidis, Newport, and Heidelberg were the most often reported MDR pathogens. Salmonella infections that were MDR were associated with excess bloodstream infections (odds ratio [OR] 1.73 95% confidence interval [CI] 1.32-2.27), more frequent hospitalizations (OR 2.51 95% CI 1.38-4.58), and higher mortality (OR 3.54 95% CI 1.10-11.40) when compared with pan-susceptible isolates. Our study suggests that MDR NTS infections have more serious health outcomes compared with pan-susceptible strains. With the emergence of MDR Salmonella strains in high-income countries, it is crucial to reduce the use of antimicrobials in animals and humans, and intervene to prevent foodborne infections.
Clinico-epidemiological profile and predictors of severe illness in young infants (0-59 days) in Ghana
Publisher: Informa UK Limited
Date: 03-2008
The epidemiology of bacteriuria and candiduria in critically ill patients
Publisher: Cambridge University Press (CUP)
Date: 24-04-2015
DOI: 10.1017/S0950268814000934
Abstract: An observational study was conducted to describe the epidemiology of bacteriuria and candiduria in the intensive care unit (ICU), and the occurrence of blood stream infection (BSI) associated with ICU-acquired positive urine culture. Between 2006 and 2011, 444 episodes of either bacteriuria or candiduria defined by positive urine culture (microorganisms ⩾10 5 c.f.u./ml) occurred in 406 patients. Three hundred and seventy-seven (85%) were hospital-acquired including 221 which were ICU-acquired (6·4 ± 0·8 episodes/1000 ICU days). Escherichia coli was the most common bacteria of both community- and ICU-acquired bacteriuria/candiduria (49·2% and 29%, respectively). Candida spp. represented 55% (129/236) of pathogens responsible for ICU-acquired positive urine cultures. Patients with ICU-acquired candiduria had greater illness severity at ICU admission than those with ICU-acquired bacteriuria (APACHE III score 79 ± 25 vs. 66 ± 31, P = 0·0015). BSI associated with ICU-acquired positive urine culture occurred in 0·15/1000 ICU days and was more often due to Candida . In this study, Candida was the most common pathogen responsible for ICU-acquired positive urine cultures and illness severity was a risk factor for candiduria in the study population.
Utilizing genomic analyses to investigate the first outbreak of van A vancomycin-resistant Enterococcus in Australia with emergence of daptomycin non-susceptibility
Publisher: Microbiology Society
Date: 03-2019
DOI: 10.1099/JMM.0.000916
Abstract: The majority of vancomycin-resistant Enterococcus faecium (VREfm) in Australia is of the vanB genotype. An outbreak of vanA VREfm emerged in our haematology/oncology unit between November 2014 and May 2015. The first case of daptomycin non-susceptible E. faecium (DNSEfm) detected was a patient with vanA VREfm bacteraemia who showed clinical failure of daptomycin therapy, prompting microbiologic testing confirming daptomycin non-susceptibility. To describe the patient profiles, antibiotic susceptibility and genetic relatedness of vanA VREfm isolates in the outbreak. Chart review of vanA VREfm colonized and infected patients was undertaken to describe the demographics, clinical features and outcomes of therapy. Whole genome sequencing of vanA VREfm isolates involved in the outbreak was conducted to assess clonality. In total, 29 s les from 24 patients tested positive for vanA VREfm (21 screening swabs and 8 clinical isolates). Five isolates were DNSEfm (four patients colonized, one patient with bacteraemia), with only one patient exposed to daptomycin previously. In silico multi-locus sequence typing of the isolates identified 25/26 as ST203, and 1/26 as ST796. Comparative genomic analysis revealed limited core genome ersity amongst the ST203 isolates, consistent with an outbreak of a single clone of vanA VREfm. Here we describe an outbreak of vanA VREfm in a haematology/oncology unit. Genomic analysis supports transmission of an ST203 vanA VRE clone within this unit. Daptomycin non-susceptibility in 5/24 patients left linezolid as the only treatment option. Daptomycin susceptibility cannot be assumed in vanA VREfm isolates and confirmatory testing is recommended.
South Asia as a Reservoir for the Global Spread of Ciprofloxacin-Resistant Shigella sonnei: A Cross-Sectional Study
Publisher: Public Library of Science (PLoS)
Date: 02-08-2016
Treatment Outcomes for Serious Infections Caused by Methicillin‐ResistantStaphylococcus aureuswith Reduced Vancomycin Susceptibility
Publisher: Oxford University Press (OUP)
Date: 15-02-2004
DOI: 10.1086/381202
Transiently silent acquired antimicrobial resistance: an emerging challenge in susceptibility testing
Publisher: Oxford University Press (OUP)
Date: 31-01-2023
DOI: 10.1093/JAC/DKAD024
Abstract: Acquisition and expression of antimicrobial resistance (AMR) mechanisms in bacteria are often associated with a fitness cost. Thus, evolutionary adaptation and fitness cost compensation may support the advance of subpopulations with a silent resistance phenotype when the antibiotic selection pressure is absent. However, reports are emerging on the transient nature of silent acquired AMR, describing genetic alterations that can change the expression of these determinants to a clinically relevant level of resistance, and the association with breakthrough infections causing treatment failures. This phenomenon of transiently silent acquired AMR (tsaAMR) is likely to increase, considering the overall expansion of acquired AMR in bacterial pathogens. Moreover, the augmented use of genotypic methods in combination with conventional phenotypic antimicrobial susceptibility testing (AST) will increasingly enable the detection of genotype and phenotype discrepancy. This review defines tsaAMR as acquired antimicrobial resistance genes with a corresponding phenotype within the wild-type distribution or below the clinical breakpoint for susceptibility for which genetic alterations can mediate expression to a clinically relevant level of resistance. References to in vivo resistance development and therapeutic failures caused by selected resistant subpopulations of tsaAMR in Gram-positive and Gram-negative pathogens are given. We also describe the underlying molecular mechanisms, including alterations in the expression, reading frame or copy number of AMR determinants, and discuss the clinical relevance concerning challenges for conventional AST.
Vancomycin therapeutics and monitoring: a contemporary approach
Publisher: Wiley
Date: 02-2013
DOI: 10.1111/IMJ.12036
Abstract: Vancomycin remains a clinically useful antibiotic despite the advent of several alternative drugs. Optimising vancomycin therapy with therapeutic drug monitoring is widely recommended. The aim of therapeutic drug monitoring is to help the clinician to achieve target pharmacodynamic parameters in the case of vancomycin, an area under the concentration time curve/minimum inhibitory concentration ratio of ≥400. Vancomycin monitoring methods can be categorised into four categories: empiric trough concentrations linear regression analysis (one-compartment model), population methods and Bayesian estimation procedures. Although the empiric trough concentrations and population methods are easy to use and require minimal resources, there are large differences in the published vancomycin model parameters. This demonstrates that there is great variance in pharmacokinetic parameters between the models and a single vancomycin model cannot be applied to all patient populations. The linear regression and Bayesian methods recommended more accurate dosage regimens however, they require additional resources such as information technology and healthcare personnel with background training in pharmacokinetics. The Bayesian methods offered additional advantages such as calculation of doses based on a single-serum concentration and optimisation of the patient's previous pharmacokinetic data to determine subsequent dosage regimens. Computerised programs, utilising the Bayesian estimation procedures, are able to achieve target concentrations in a greater percentage of patients earlier in the course of therapy than the empiric trough concentrations and population methods. We recommend the use of these programs providing there is appropriate expertise available to make appropriate recommendations.
Pilot study of a combined genomic and epidemiologic surveillance program for hospital-acquired multidrug-resistant pathogens across multiple hospital networks in Australia
Publisher: Cambridge University Press (CUP)
Date: 26-11-2020
Abstract: To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission. Pilot prospective multicenter surveillance study. The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals. All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data. In total, 408 isolates were collected from 358 patients 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure. Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients). Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.
Increasing incidence of invasive nontyphoidal Salmonella infections in Queensland, Australia, 2007-2016
Publisher: Public Library of Science (PLoS)
Date: 18-03-2018
The dominant Australian community-acquired methicillin-resistant Staphylococcus aureus clone ST93-IV [2B] is highly virulent and genetically distinct
Publisher: Public Library of Science (PLoS)
Date: 03-10-2011
Mobile phones and computer keyboards: unlikely reservoirs of multidrug-resistant organisms in the tertiary intensive care unit
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.JHIN.2018.02.013
Abstract: Few studies have used molecular epidemiological methods to study transmission links to clinical isolates in intensive care units. Ninety-four multidrug-resistant organisms (MDROs) cultured from routine specimens from intensive care unit (ICU) patients over 13 weeks were stored (11 meticillin-resistant Staphylococcus aureus (MRSA), two vancomycin-resistant enterococci and 81 Gram-negative bacteria). Medical staff personal mobile phones, departmental phones, and ICU keyboards were swabbed and cultured for MDROs MRSA was isolated from two phones. Environmental and patient isolates of the same genus were selected for whole genome sequencing. On whole genome sequencing, the mobile phone isolates had a pairwise single nucleotide polymorphism (SNP) distance of 183. However, >15,000 core genome SNPs separated the mobile phone and clinical isolates. In a low-endemic setting, mobile phones and keyboards appear unlikely to contribute to hospital-acquired MDROs.
Mycolactone Gene Expression Is Controlled by Strong SigA-Like Promoters with Utility in Studies of Mycobacterium ulcerans and Buruli Ulcer
Publisher: Public Library of Science (PLoS)
Date: 24-11-2009
Morbidity from in-hospital complications is greater than treatment failure in patients with Staphylococcus aureus bacteraemia
Publisher: Springer Science and Business Media LLC
Date: 05-03-2018
Blue light enhances astaxanthin biosynthesis metabolism and extraction efficiency in Haematococcus pluvialis by inducing haematocyst germination
Publisher: Elsevier BV
Date: 11-2018
Quality and Validity of Diet Quality Indices for Use in Australian Contexts: A Systematic Review
Publisher: Cambridge University Press (CUP)
Date: 16-12-2021
DOI: 10.1017/S0007114521004943
Abstract: Diet quality indices (DQIs) are tools used to evaluate the overall diet quality against dietary guidelines or known healthy dietary patterns. This review aimed to evaluate DQIs and their validation processes to facilitate decision making in the selection of appropriate DQI for use in Australian contexts. A search of CINAHL, PubMed and Scopus electronic databases was conducted for studies published between January 2010 and May 2020, which validated a DQI, measuring 1 dimension of diet quality (adequacy, balance, moderation, variety) and was applicable to the Australian context. Data on constructs, scoring, weighting and validation methods (construct validity, criterion validity, reliability and reproducibility) were extracted and summarised. The quality of the validation process was evaluated using COnsensus-based Standards for the selection of health Measurement INstruments Risk of Bias and Joanna Briggs Appraisal checklists. The review identified twenty-seven indices measuring adherence to: national dietary guidelines ( n 13), Mediterranean Diet ( n 8) and specific population recommendations and chronic disease risk ( n 6). Extensiveness of the validation process varied widely across and within categories. Construct validity was the most strongly assessed measurement property, while evaluation of measurement error was frequently inadequate. DQIs should capture multiple dimensions of diet quality, possess a reliable scoring system and demonstrate adequate evidence in their validation framework to support use in the intended context. Researchers need to understand the limitations of newly developed DQIs and interpret results in view of the validation evidence. Future research on DQIs is indicated to improve evaluation of measurement error, reproducibility and reliability.
Comparison between jet and paddlewheel mixing for the cultivation of microalgae in anaerobic digestate of piggery effluent (ADPE)
Publisher: Elsevier BV
Date: 11-2018
Increased Detection of Pharyngeal and Rectal Gonorrhea in Men Who Have Sex With Men After Transition From Culture To Nucleic Acid Amplification Testing
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2017
Implementation and evaluation of a novel real-time multiplex assay for SARS-CoV-2: in-field learnings from a clinical microbiology laboratory
Publisher: Elsevier BV
Date: 12-2020
Outbreak of vanB vancomycin-resistant Enterococcus faecium colonization in a neonatal service.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.AJIC.2015.05.047
Abstract: To describe successful termination of an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) colonization within a neonatal service. Multisite neonatal intensive care unit and special care nurseries within a single health care service. Forty-four cases of VREfm-colonized neonatal inpatients-including 2 clinical isolates (eye swab and catheter-urine specimen) and 42 screening isolates. Active surveillance cultures, patient isolation, contact precautions, enhanced environment cleaning, and staff and parent education. Whole genome sequencing and multilocus sequence typing were used to characterize the outbreak and refine infection control procedures. Peak prevalence of VREfm colonization across all sites was 31% upon discovery of the outbreak. Subsequent to the intervention, transmission was halted within 8 weeks and no further isolates of the outbreak strain have been detected as of 12 months following outbreak cessation. Environmental swabs revealed VREfm colonization of baby-weighing scales, a baby bath, and a pharmacy refrigerator within the neonatal intensive care unit. All isolates were of a single multilocus sequence type (sequence type 796) and highly clonal at the core genome level. Bundled infection control interventions were effective in rapidly terminating a clonal outbreak of sequence type 796 VREfm colonization within a neonatal inpatient service. Strain-typing and active surveillance cultures were critical in guiding the management of this outbreak. The closed environment of a neonatal unit likely facilitated eradication of the patient and environment reservoirs of VREfm colonization.
Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin
Publisher: Cold Spring Harbor Laboratory
Date: 05-03-2023
DOI: 10.1101/2023.03.01.23286614
Abstract: Bacterial pathogens such as vancomycin-resistant Enterococcus faecium (VREfm) that are resistant to almost all antibiotics are among the top global threats to human health. Daptomycin is a new last-resort antibiotic for VREfm infections with a novel mode-of-action, but for which resistance has surprisingly and alarmingly been widely reported. The causes of such a rapid emergence of resistance to this novel antibiotic have been unclear. Here we show that the use of rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in liver disease patients, is causing resistance to this last-resort antibiotic in VREfm. We show that mutations within the bacterial RNA polymerase complex confer cross- resistance to both rifaximin and daptomycin. Furthermore, VREfm with these mutations are spread globally across at least 5 continents and 20 countries, making this a major yet previously unrecognised mechanism of resistance. Until now, rifaximin has been considered ‘low-risk’ for development of antibiotic resistance. Our study shows this is not the case and that widespread rifaximin use may be compromising the clinical efficacy of daptomycin, one of the major last-resort interventions for multidrug resistant pathogens. These findings demonstrate that unanticipated antibiotic cross-resistance may potentially undermine global strategies designed to preserve the clinical use of last-resort antibiotics.
Evidence based practice guidelines for the nutritional management of chronic kidney disease
Publisher: Wiley
Date: 21-08-2006
The evolution and international spread of extensively drug resistant Shigella sonnei
Publisher: Springer Science and Business Media LLC
Date: 08-04-2023
DOI: 10.1038/S41467-023-37672-W
Abstract: Shigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common including against World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin. Recently, an MSM-associated outbreak of extended-spectrum β-lactamase producing, extensively drug resistant S. sonnei was reported in the United Kingdom. Here, we aimed to identify the genetic basis, evolutionary history, and international dissemination of the outbreak strain. Our genomic epidemiological analyses of 3,304 isolates from the United Kingdom, Australia, Belgium, France, and the United States of America revealed an internationally connected outbreak with a most recent common ancestor in 2018 carrying a low-fitness cost resistance plasmid, previously observed in travel associated sublineages of S. flexneri . Our results highlight the persistent threat of horizontally transmitted antimicrobial resistance and the value of continuing to work towards early and open international sharing of genomic surveillance data.
Population genetics and the evolution of virulence in Staphylococcus aureus
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.MEEGID.2013.04.026
Abstract: Staphylococcus aureus is one of the most important human pathogens, causing life-threatening infection in the community and hospital setting. The population genetics of S. aureus and the evolution of virulence is the focus of this review. We describe the various techniques in determining S. aureus population structure and discuss the insights gained from whole genome sequencing of various S. aureus strains. The emergence of community-acquired, methicillin-resistant S. aureus provides a framework for the discussion on evolution of virulence, and the role of horizontal gene transfer in the development of virulence and antibiotic resistance is explored. The knowledge generated from population genetics has the potential to inform strategies to assist in the prevention or treatment of this highly successful human pathogen.
Transcriptome-wide analysis of Chlorella reveals auxin-induced carotenogenesis pathway in green microalgae
Publisher: Elsevier BV
Date: 2019
Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia
Publisher: American Medical Association (AMA)
Date: 11-02-2020
Case Report: Confirmation by Metagenomic Sequencing of Visceral Leishmaniasis in an Immunosuppressed Returned Traveler
Publisher: American Society of Tropical Medicine and Hygiene
Date: 04-11-2020
Absence of high priority critically important antimicrobial resistance in Salmonella sp. isolated from Australian commercial egg layer environments
Publisher: Elsevier BV
Date: 02-2021
Adaptive change inferred from genomic population analysis of the ST93 epidemic clone of community-associated methicillin-resistant Staphylococcus aureus
Publisher: Oxford University Press (OUP)
Date: 29-01-2014
DOI: 10.1093/GBE/EVU022
Whatʼs new in the treatment of serious MRSA infection?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2014
Recognition and management of infections caused by vancomycin‐intermediate Staphylococcus aureus (VISA) and heterogenous VISA (hVISA)
Publisher: Wiley
Date: 04-11-2005
DOI: 10.1111/J.1444-0903.2005.00986.X
Abstract: Vancomycin resistance in Staphylococcus aureus has recently emerged as an important clinical problem with implications for laboratory detection and clinical management of patients infected with resistant strains. To date, low-level vancomycin resistance in the form of vancomycin-intermediate S. aureus (VISA) and heterogenous vancomycin-intermediate S. aureus (hVISA) have been more common, with only four cases of true vancomycin resistant S. aureus (VRSA) reported. This article reviews current knowledge about the epidemiology, clinical manifestations and optimal management of hVISA and VISA infections. VISA and hVISA have now been reported from many countries, and these strains tend to occur in patients with significant comorbidities and previous antibiotic exposure. Despite the difficulties in laboratory detection, there are increasing data linking VISA and hVISA to failure of glycopeptide antimicrobial therapy. Aggressive surgical intervention and non-glycopeptide-based antimicrobial therapy appears to improve outcomes for patients infected with these low-level vancomycin-resistant strains. Clinicians and diagnostic laboratories need to be aware of VISA and hVISA as a clinical problem, and consider aggressive surgical debridement and non-glycopeptide-based therapy where infections with such strains are suspected or proven.
Genomic investigation of Staphylococcus aureus recovered from Gambian women and newborns following an oral dose of intra-partum azithromycin
Publisher: Oxford University Press (OUP)
Date: 19-08-2019
DOI: 10.1093/JAC/DKZ341
Abstract: Oral azithromycin given during labour reduces carriage of bacteria responsible for neonatal sepsis, including Staphylococcus aureus. However, there is concern that this may promote drug resistance. Here, we combine genomic and epidemiological data on S. aureus isolated from mothers and babies in a randomized intra-partum azithromycin trial (PregnAnZI) to describe bacterial population dynamics and resistance mechanisms. Participants from both arms of the trial, who carried S. aureus in day 3 and day 28 s les post-intervention, were included. Sixty-six S. aureus isolates (from 7 mothers and 10 babies) underwent comparative genome analyses and the data were then combined with epidemiological data. Trial registration (main trial): ClinicalTrials.gov Identifier NCT01800942. Seven S. aureus STs were identified, with ST5 dominant (n = 40, 61.0%), followed by ST15 (n = 11, 17.0%). ST5 predominated in the placebo arm (73.0% versus 49.0%, P = 0.039) and ST15 in the azithromycin arm (27.0% versus 6.0%, P = 0.022). In azithromycin-resistant isolates, msr(A) was the main macrolide resistance gene (n = 36, 80%). Ten study participants, from both trial arms, acquired azithromycin-resistant S. aureus after initially harbouring a susceptible isolate. In nine (90%) of these cases, the acquired clone was an msr(A)-containing ST5 S. aureus. Long-read sequencing demonstrated that in ST5, msr(A) was found on an MDR plasmid. Our data reveal in this Gambian population the presence of a dominant clone of S. aureus harbouring plasmid-encoded azithromycin resistance, which was acquired by participants in both arms of the study. Understanding these resistance dynamics is crucial to defining the public health drug resistance impacts of azithromycin prophylaxis given during labour in Africa.
State-wide genomic epidemiology investigations of COVID-19 in healthcare workers in 2020 Victoria, Australia: Qualitative thematic analysis to provide insights for future pandemic preparedness
Publisher: Elsevier BV
Date: 08-2022
Use of bacterial whole-genome sequencing to understand and improve the management of invasive Staphylococcus aureus infections.
Publisher: Informa UK Limited
Date: 21-09-2016
DOI: 10.1080/14787210.2016.1233815
Abstract: Management of invasive Staphylococcus aureus infections is complex. Dramatic improvements in bacterial whole genome sequencing (WGS) offer new opportunities for personalising the treatment of S. aureus infections. Areas covered: We address recent achievements in S. aureus genomics, describe genetic determinants of antibiotic resistance and summarise studies that have defined molecular characteristics associated with risk and outcome of S. aureus invasive infections. Potential clinical use of WGS for resistance prediction, infection outcome stratification and management of persistent /relapsing infections is critically discussed. Expert commentary: WGS is not only providing invaluable information to track the emergence and spread of important S. aureus clones, but also allows rapid determination of resistance genotypes in the clinical environment. An evolving opportunity is to infer clinically important outcomes and optimal therapeutic approaches from widely available S. aureus genome data, with the goal of in idualizing management of invasive S. aureus infections.
Genomic analysis reveals a point mutation in the two-component sensor gene graS that leads to intermediate vancomycin resistance in clinical Staphylococcus aureus
Publisher: American Society for Microbiology
Date: 10-2008
DOI: 10.1128/AAC.01613-07
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA), once restricted to hospitals, is spreading rapidly through the wider community. Resistance to vancomycin, the principal drug used to treat MRSA infections, has only recently emerged, is mainly low level, and characteristically appears during vancomycin therapy (vancomycin-intermediate S. aureus [VISA] and hetero-resistant VISA). This phenomenon suggests the adaptation of MRSA through mutation, although defining the mutations leading to resistance in clinical isolates has been difficult. We studied a vancomycin-susceptible clinical MRSA isolate (MIC of 1 μg/ml) and compared it with an isogenic blood culture isolate from the same patient, despite 42 days of vancomycin treatment (MIC of 4 μg/ml). A whole-genome sequencing approach allowed the nearly complete assembly of the genome sequences of the two isolates and revealed only six nucleotide substitutions in the VISA strain compared with the parent strain. One mutation occurred in graS , encoding a putative two-component regulatory sensor, leading to a change from a polar to a nonpolar amino acid (T136I) in the conserved histidine region of the predicted protein. Replacing the graS allele of the vancomycin-susceptible parent strain with the graS allele from the VISA derivative resulted in increased vancomycin resistance at a level between those of the vancomycin-susceptible S. aureus and VISA clinical isolates, confirming a role for graRS in VISA. Our study suggests that MRSA is able to develop clinically significant vancomycin resistance via a single point mutation, and the two-component regulatory system graRS is a key mediator of this resistance. However, additional mutations are likely required to express the full VISA phenotype.
Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria
Publisher: Springer Science and Business Media LLC
Date: 18-03-2023
DOI: 10.1038/S41467-023-37200-W
Abstract: Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20–40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli , Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes . Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research.
Good Clinical Outcomes but High Rates of Adverse Reactions during Linezolid Therapy for Serious Infections: a Proposed Protocol for Monitoring Therapy in Complex Patients
Publisher: American Society for Microbiology
Date: 04-2006
DOI: 10.1128/AAC.50.4.1599-1602.2006
Abstract: We assessed the toxicity and clinical outcomes associated with linezolid therapy (mean duration, 29 ± 28 days range, 8 to 185 days) in 44 patients with serious gram-positive infections. Although a clinical cure was achieved in 73% of the cases, 28/44 (64%) had adverse reactions (thrombocytopenia, n = 13 anemia, n = 7 gastrointestinal, n = 12 peripheral neuropathy, n = 1 serotonin syndrome, n = 1), such that a systematic monitoring protocol was developed.
Public health implementation of pathogen genomics: the role for accreditation and application of ISO standards
Publisher: Microbiology Society
Date: 17-08-2023
Abstract: Pathogen genomics has transitioned rapidly from the research setting into a powerful tool now routinely used in public health microbiology, for surveillance, outbreak investigations and disease control. As these investigations can have significant public health, treatment and legal impacts, we must ensure the accuracy of these results through validation of testing processes. For laboratories working in this space, it is important to approach this work with a quality and accreditation framework in mind, working towards implementation of quality systems and test validation that meet international regulatory standards. Here we outline the key international standards and processes that lead toward accreditation for pathogen genomics.
Appropriate use of oral nutritional supplements in stages 4–5 chronic kidney disease
Publisher: Mark Allen Group
Date: 02-05-2015
DOI: 10.12968/JORN.2015.7.3.115
Abstract: Implementation strategies for using oral nutritional supplements (ONS) in patients with stages 4-5 chronic kidney disease (CKD) are lacking in the UK and current international recommendations 1 are not tailored to the dietetic-led nutrition services prominent in the UK. A recent meeting of the Renal Nutrition Group (RNG) of the British Dietetic Association (BDA) identified a need for clarity on the use of ONS in these patients and as a result a group of seven renal dietitians, together with a general practitioner, met to discuss and reach agreement on a simple step-by-step consensus algorithm to guide the appropriate use of ONS in patients with stages 4-5 CKD.
Multicentre randomised double-blind placebo controlled trial of combination vancomycin and cefazolin surgical antibiotic prophylaxis: the Australian surgical antibiotic prophylaxis (ASAP) trial
Publisher: BMJ
Date: 11-2019
DOI: 10.1136/BMJOPEN-2019-033718
Abstract: Resistant Gram-positive organisms, such as methicillin-resistant staphylococci, account for a significant proportion of infections following joint replacement surgery. Current surgical antimicrobial prophylaxis guidelines recommend the use of first-generation or second-generation cephalosporin antibiotics, such as cefazolin. Cefazolin, however, does not prevent infections due to these resistant organisms therefore, new prevention strategies need to be examined. One proposed strategy is to combine a glycopeptide antibiotic with cefazolin for prophylaxis. The clinical benefit and cost-effectiveness of this combination therapy compared with usual therapy, however, have not been established. This randomised, double-blind, parallel, superiority, placebo-controlled, phase 4 trial will compare the incidence of all surgical site infections (SSIs) including superficial, deep and organ/space (prosthetic joint) infections, safety and cost-effectiveness of surgical prophylaxis with cefazolin plus vancomycin to that with cefazolin plus placebo. The study will be performed in patients undergoing joint replacement surgery. In the microbiological sub-studies, we will examine the incidence of SSIs in participants with preoperative staphylococci colonisation (Sub-Study 1) and incidence of VRE acquisition (Sub-Study 2). The trial will recruit 4450 participants over a 4-year period across 13 orthopaedic centres in Australia. The primary outcome is the incidence of SSI at 90 days post index surgery. Secondary outcomes include the incidence of SSI according to joint and microorganism and other healthcare associated infections. Safety endpoints include the incidence of acute kidney injury, hypersensitivity reactions and all-cause mortality. The primary and secondary analysis will be a modified intention-to-treat analysis consisting of all randomised participants who undergo eligible surgery. We will also perform a per-protocol analysis. The study protocol was reviewed and approved by The Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/102) on 9 July 2018. Study findings will be disseminated in the printed media, and learnt forums. ACTRN12618000642280
Extensively Drug-Resistant Shigellosis in Australia among Men Who Have Sex with Men
Publisher: Massachusetts Medical Society
Date: 19-12-2019
DOI: 10.1056/NEJMC1910648
Mycobacterium ulcerans low infectious dose and mechanical transmission support insect bites and puncturing injuries in the spread of Buruli ulcer
Publisher: Public Library of Science (PLoS)
Date: 14-04-2017
Evaluation of the ResistancePlus GC (beta) assay: a commercial diagnostic test for the direct detection of ciprofloxacin susceptibility or resistance in Neisseria gonorrhoeae
Publisher: Oxford University Press (OUP)
Date: 20-03-2019
DOI: 10.1093/JAC/DKZ108
Abstract: To evaluate the performance of the ResistancePlus GC (beta) assay for the simultaneous detection of Neisseria gonorrhoeae and gyrA S91 markers of resistance (S91F) and susceptibility (WT) to ciprofloxacin, from both clinical specimens and isolates. Performance was assessed on several s le banks, including N. gonorrhoeae isolates (n = 822), non-gonococcal isolates (n = 110), N. gonorrhoeae-positive clinical specimens (n = 402) and N. gonorrhoeae-negative specimens (n = 290). Results were compared with previous testing data, including S91 genotyping and phenotypic resistance profiles. Overall, the assay demonstrated 100% sensitivity for N. gonorrhoeae detection in clinical isolates. For gyrA S91 mutation detection in clinical isolates, the assay showed 100% sensitivity/specificity compared with the genotype, and >99%/>97% sensitivity/specificity when compared with phenotype. For positive clinical specimens, the assay demonstrated >96% sensitivity for N. gonorrhoeae detection and 100% sensitivity/specificity for gyrA S91 mutation detection. The assay demonstrated >99% specificity for N. gonorrhoeae detection against non-gonococcal isolates and 100% specificity for negative clinical specimens. The ResistancePlus GC (beta) assay is suitable for the detection of N. gonorrhoeae and gyrA markers associated with resistance/susceptibility to ciprofloxacin directly in clinical s les. This assay could be implemented for the in idualized treatment of gonorrhoea infections as well as to enhance current antimicrobial resistance surveillance methods.
Increasing tolerance of hospital Enterococcus faecium to handwash alcohols
Publisher: American Association for the Advancement of Science (AAAS)
Date: 08-2018
DOI: 10.1126/SCITRANSLMED.AAR6115
Abstract: Alcohol-based disinfectants and particularly hand rubs are a key way to control hospital infections worldwide. Such disinfectants restrict transmission of pathogens, such as multidrug-resistant
A statistical genomics framework to trace bacterial genomic predictors of clinical outcomes in Staphylococcus aureus bacteraemia
Publisher: Cold Spring Harbor Laboratory
Date: 22-04-2022
DOI: 10.1101/2022.04.21.22273941
Abstract: Outcomes for patients with severe bacterial infections are determined by the interplay between host, pathogen, and treatments. Most notably, patient age and antibiotic resistance contributes significantly to poor outcomes. While human genomics studies have provided insights into the host genetic factors impacting outcomes of Staphylococcus aureus infections, comparatively little is known about S. aureus genotypes and disease severity. Building on the idea that bacterial pathoadaptation is a key driver of clinical outcomes, we develop a new genome-wide association study (GWAS) framework to identify adaptive bacterial mutations associated with clinical treatment failure and mortality in three large and independent S. aureus bacteraemia cohorts, comprising 1358 episodes. We discovered S. aureus loci with previously undescribed convergent mutations linked to both poorer infection outcomes and reduced susceptibility to vancomycin. Our research highlights the potential of vancomycin-selected mutations and vancomycin MIC as key explanatory variables to predict SAB severity. The contribution of bacterial variation was much lower for clinical outcomes (heritability 5%), however, GWAS allowed us to identify additional, MIC-independent candidate pathogenesis loci. Using supervised machine-learning, we were able to quantify the predictive potential of these adaptive S. aureus signatures, along with host determinants of bacteraemia outcomes. The statistical genomics framework we have developed is a powerful means to capture adaptive mutations and find bacterial factors that influence and predict severe infections. Our findings underscore the importance of systematically collected, rich clinical and microbiological data to understand bacterial mechanisms promoting treatment failure.
Mortality and morbidity following exercise-based renal rehabilitation in patients with chronic kidney disease: the effect of programme completion and change in exercise capacity
Publisher: Oxford University Press (OUP)
Date: 30-11-2018
DOI: 10.1093/NDT/GFY351
Dumb and Dumber--The Potential Waste of a Useful Antistaphylococcal Agent: Emerging Fusidic Acid Resistance in Staphylococcus aureus
Publisher: Oxford University Press (OUP)
Date: 02-2006
DOI: 10.1086/499365
Abstract: Fusidic acid has activity against a range of pathogens but has mainly been used to treat staphylococcal infections. Fusidic acid monotherapy, especially topical preparations, has been strongly associated with the emergence of fusidic acid resistance among both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus. Key resistance determinants include mutations in the fusA gene, which encodes elongation factor G, and plasmid-mediated resistance (i.e., acquisition of resistance gene fusB). Clonal outbreaks of fusidic acid-resistant S. aureus have been noted throughout the United Kingdom and Europe, such that the efficacy of fusidic acid is threatened. Fusidic acid in combination with other agents, such as rif icin, has proven effective for difficult-to-treat MRSA infections and provides a convenient oral alternative to oxazolidinones. Ensuring that systemic fusidic acid is always used in combination and that the use of topical fusidic acid is either abolished or restricted will be vital if we are to prevent the loss of this potentially useful agent.
A high-throughput cytotoxicity screening platform revealsagr-independent mutations in bacteraemia-associatedStaphylococcus aureusthat promote intracellular persistence
Publisher: Cold Spring Harbor Laboratory
Date: 13-12-2022
DOI: 10.1101/2022.12.11.519971
Abstract: Staphylococcus aureus infections are associated with high mortality rates. Often considered an extracellular pathogen, S. aureus can persist and replicate within host cells, evading immune responses and causing host cell death. Classical methods for assessing S. aureus cytotoxicity are limited by testing culture supernatants and endpoint measurements that do not capture the phenotypic ersity of intracellular bacteria. Using a well-established epithelial cell line model, we have developed a platform called InToxSa ( In tracellular Tox icity of S. a ureus ) to quantify intracellula cytotoxic S. aureus phenotypes. Studying a panel of 387 S. aureus bacteraemia isolates, and combined with comparative, statistical and functional genomics, our platform identified mutations in S. aureus clinical isolates that reduced bacterial cytotoxicity and promoted intracellular persistence. In addition to numerous convergent mutations in the Agr quorum sensing system, our approach detected mutations in other loci that also impacted cytotoxicity and intracellular persistence. We discovered that clinical mutations in ausA, encoding the aureusimine non-ribosomal peptide synthetase, reduced S. aureus cytotoxicity and increased intracellular persistence. InToxSa is a versatile, high-throughput cell-based phenomics platform and we showcase its utility by identifying clinically relevant S. aureus pathoadaptive mutations that promote intracellular residency.
Reply to internet-based solutions for analysis of next-generation sequence data
Publisher: American Society for Microbiology
Date: 09-2013
DOI: 10.1128/JCM.01393-13
Risk for chronic kidney disease increases with obesity: Health Survey for England 2010
Publisher: Cambridge University Press (CUP)
Date: 06-03-2015
DOI: 10.1017/S1368980015000488
Abstract: Studies of the relationship between obesity and chronic kidney disease (CKD) in nationally representative population s les are limited. Our study aimed to determine if overweight and obesity were independently associated with the risk for CKD in the 2010 Health Survey for England (HSE). The HSE is an annually conducted cross-sectional study. In 2010 serum creatinine was included to determine the incidence of CKD in the population. CKD was defined as estimated glomerular filtration rate (eGFR) ml/min per 1·73 m 2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Multivariable logistic regression models were developed to calculate odds ratios and 95 % confidence intervals for CKD risk by BMI (reference category: BMI=18·5–24·9 kg/m 2 ) and adjusted for age, gender, ethnicity, smoking, diabetes and hypertension. A random s le of nationally representative households in England. Adults ( n 3463) with calculable eGFR and BMI were included. The prevalence of CKD was 5·9 %. The risk of CKD was over 2·5 times higher in obese participants compared with normal-weight participants in the fully adjusted model (BMI=30·0–39·9 kg/m 2 : adjusted OR=2·78 (95 % CI 1·75, 4·43) BMI ≥ 40·0 kg/m 2 : adjusted OR=2·68 (95 % CI 1·05, 6·85)). Obesity is associated with an increased risk of CKD in a national s le of the UK population, even after adjustment for known CKD risk factors, which may have implications for CKD screening and future national health service planning and delivery.
Genomic analysis of ST88 community-acquired methicillin resistant Staphylococcus aureus in Ghana.
Publisher: PeerJ
Date: 28-02-2017
DOI: 10.7717/PEERJ.3047
Abstract: The emergence and evolution of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) strains in Africa is poorly understood. However, one particular MRSA lineage called ST88, appears to be rapidly establishing itself as an “African” CA-MRSA clone. In this study, we employed whole genome sequencing to provide more information on the genetic background of ST88 CA-MRSA isolates from Ghana and to describe in detail ST88 CA-MRSA isolates in comparison with other MRSA lineages worldwide. We first established a complete ST88 reference genome (AUS0325) using PacBio SMRT sequencing. We then used comparative genomics to assess relatedness among 17 ST88 CA-MRSA isolates recovered from patients attending Buruli ulcer treatment centres in Ghana, three non-African ST88s and 15 other MRSA lineages. We show that Ghanaian ST88 forms a discrete MRSA lineage (harbouring SCC mec- IV [2B]). Gene content analysis identified five distinct genomic regions enriched among ST88 isolates compared with the other S. aureus lineages. The Ghanaian ST88 isolates had only 658 core genome SNPs and there was no correlation between phylogeny and geography, suggesting the recent spread of this clone. The lineage was also resistant to multiple classes of antibiotics including β -lactams, tetracycline and chlor henicol. This study reveals that S. aureus ST88-IV is a recently emerging and rapidly spreading CA-MRSA clone in Ghana. The study highlights the capacity of small snapshot genomic studies to provide actionable public health information in resource limited settings. To our knowledge this is the first genomic assessment of the ST88 CA-MRSA clone.
Prolonged Exposure to β-Lactam Antibiotics Reestablishes Susceptibility of Daptomycin-Nonsusceptible Staphylococcus aureus to Daptomycin
Publisher: American Society for Microbiology
Date: 20-08-2020
DOI: 10.1128/AAC.00890-20
Abstract: Daptomycin-nonsusceptible (DAP-NS) Staphylococcus aureus often exhibits gain-in-function mutations in the mprF gene (involved in positive surface charge maintenance). Standard β-lactams, although relatively inactive against methicillin-resistant S. aureus (MRSA), may prevent the emergence of mprF mutations and DAP-NS. We determined if β-lactams might also impact DAP-NS isolates already possessing an mprF mutation to revert them to DAP-susceptible (DAP-S) phenotypes and, if so, whether this is associated with specific penicillin-binding protein (PBP) targeting.
Sample pooling on the Cepheid Xpert® Xpress SARS-CoV-2 assay
Publisher: Elsevier BV
Date: 02-2021
Determining research priorities for clinician-initiated trials in infectious diseases.
Publisher: AMPCo
Date: 03-2013
DOI: 10.5694/MJA12.11703
Abstract: To determine research priorities of infectious diseases physicians for clinician-initiated randomised controlled trials (RCTs). Online survey of infectious diseases physicians in Australia and New Zealand. Research priorities for, and perceived barriers to, clinician-initiated RCTs. 122/550 infectious diseases physicians (22%) responded to the survey. The five highest ranked proposals for clinician-initiated RCTs were in the areas of prosthetic joint infections, septic arthritis and osteomyelitis of native joints, Staphylococcus aureus bloodstream infections, diabetic foot infections and the treatment of serious multiresistant, gram-negative bacterial infections. Lack of funding was the most important perceived barrier to participation in clinician-initiated RCTs. The research focus of infectious diseases physicians - optimal treatment of commonly encountered serious infections - highlights a lack of well conducted RCTs in this area.
Continuous-infusion penicillin home-based therapy for serious infections due to penicillin-susceptible pathogens
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.IJANTIMICAG.2006.10.018
Abstract: To evaluate the feasibility of continuous-infusion (CI) penicillin in the treatment of serious bacterial infections, consecutive adult patients with deep-seated infections due to penicillin-susceptible pathogens were treated with CI aqueous penicillin G in a home-based programme, and their treatment outcomes were reviewed. Thirty-one patients with microbiologically proven infections completed the planned course of treatment. Twenty of 31 (65%) were followed for at least 2 months thereafter, and all remained free of relapse. One patient had fever attributable to penicillin hypersensitivity, two patients developed catheter-site infections and one patient developed catheter-related bacteraemia. Thus, CI penicillin is feasible for the home-based treatment of a variety of deep-seated infections with minimal toxicity.
A nonclonal outbreak of vancomycin-sensitive Enterococcus faecalis bacteremia in a neonatal intensive care unit
Publisher: Cambridge University Press (CUP)
Date: 05-08-2019
DOI: 10.1017/ICE.2019.202
Abstract: To describe an outbreak of bacteremia caused by vancomycin-sensitive Enterococcus faecalis (VSEfe). An investigation by retrospective case control and molecular typing by whole-genome sequencing (WGS). A tertiary-care neonatal unit in Melbourne, Australia. Risk factors for 30 consecutive neonates with VSEfe bacteremia from June 2011 to December 2014 were analyzed using a case control study. Controls were neonates matched for gestational age, birth weight, and year of birth. Isolates were typed using WGS, and multilocus sequence typing (MLST) was determined. Bacteremia for case patients occurred at a median time after delivery of 23.5 days (interquartile range, 14.9–35.8). Previous described risk factors for nosocomial bacteremia did not contribute to excess risk for VSEfe. WGS typing results designated 43% ST179 as well as 14 other sequence types, indicating a polyclonal outbreak. A multimodal intervention that included education, insertion checklists, guidelines on maintenance and access of central lines, adjustments to the late onset sepsis antibiotic treatment, and the introduction of diaper bags for disposal of soiled diapers after being handled inside the bed, led to termination of the outbreak. Typing using WGS identified this outbreak as predominately nonclonal and therefore not due to cross transmission. A multimodal approach was then sought to reduce the incidence of VSEfe bacteremia.
An ISO-certified genomics workflow for identification and surveillance of antimicrobial resistance
Publisher: Springer Science and Business Media LLC
Date: 04-01-2023
DOI: 10.1038/S41467-022-35713-4
Abstract: Realising the promise of genomics to revolutionise identification and surveillance of antimicrobial resistance (AMR) has been a long-standing challenge in clinical and public health microbiology. Here, we report the creation and validation of abritAMR , an ISO-certified bioinformatics platform for genomics-based bacterial AMR gene detection. The abritAMR platform utilises NCBI’s AMRFinderPlus , as well as additional features that classify AMR determinants into antibiotic classes and provide customised reports. We validate abritAMR by comparing with PCR or reference genomes, representing 1500 different bacteria and 415 resistance alleles. In these analyses, abritAMR displays 99.9% accuracy, 97.9% sensitivity and 100% specificity. We also compared genomic predictions of phenotype for 864 Salmonella spp. against agar dilution results, showing 98.9% accuracy. The implementation of abritAMR in our institution has resulted in streamlined bioinformatics and reporting pathways, and has been readily updated and re-verified. The abritAMR tool and validation datasets are publicly available to assist laboratories everywhere harness the power of AMR genomics in professional practice.
Heterogeneity of genetic pathways toward daptomycin nonsusceptibility in Staphylococcus aureus determined by adjunctive antibiotics
Publisher: American Society for Microbiology
Date: 05-2015
DOI: 10.1128/AAC.04990-14
Abstract: Daptomycin is increasingly used in combination with other antibiotics to enhance antimicrobial efficacy and/or to mitigate the emergence of daptomycin nonsusceptibility (DNS). This study used a clinical methicillin-resistant Staphylococcus aureus (MRSA) strain in which DNS emerged upon therapy to examine the influence of antibiotic combinations on the development of mutations in specific genes ( mprF , rpoBC , dltA , cls2 , and yycFG ) previously associated with DNS. Whole genomes of bacteria obtained following 28 days of in vitro exposure to daptomycin with or without adjunctive clarithromycin, linezolid, oxacillin, or trimethoprim-sulfamethoxazole were sequenced, and the sequences were compared to that of the progenitor isolate. The addition of oxacillin to medium containing daptomycin prevented the emergence of mprF mutation but did not prevent rpoBC mutation ( P 0.01). These isolates maintained susceptibility to daptomycin during the combined exposure (median MIC, 1 mg/liter). Daptomycin plus clarithromycin or linezolid resulted in low-level (1.5 to 8 mg/liter) and high-level (12 to 96 mg/liter) DNS, respectively, and did not prevent mprF mutation. However, these same combinations prevented rpoBC mutation. Daptomycin alone or combined with linezolid or trimethoprim-sulfamethoxazole resulted in high-level DNS and mutations in mprF plus rpoBC , cls2 , and yycFG . Combining daptomycin with different antimicrobials alters the mutational space available for DNS development, thereby favoring the development of predictable collateral susceptibilities.
Evaluation of the Xpert™ MRSA/SA Blood Culture assay for the detection of Staphylococcus aureus including strains with reduced vancomycin susceptibility from blood culture specimens
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.DIAGMICROBIO.2011.02.006
Abstract: The Xpert MRSA/SA Blood Culture (BC) assay (Cepheid, Sunnyvale, CA) was prospectively compared to culture and found to have excellent specificity for both Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in BC specimens with a sensitivity of 75% (3/4) and 100% (17/17), respectively. Among 28 heterogeneous vancomycin-intermediate S. aureus (hVISA)/VISA spiked BCs, the assay correctly identified 84.6% VISA and 80% hVISA isolates as MRSA.
Validation of a single-step, single-tube reverse transcription loop-mediated isothermal amplification assay for rapid detection of SARS-CoV-2 RNA
Publisher: Microbiology Society
Date: 09-2020
DOI: 10.1099/JMM.0.001238
Abstract: Introduction. The SARS-CoV-2 pandemic of 2020 has resulted in unparalleled requirements for RNA extraction kits and enzymes required for virus detection, leading to global shortages. This has necessitated the exploration of alternative diagnostic options to alleviate supply chain issues. Aim. To establish and validate a reverse transcription loop-mediated isothermal lification (RT- LAMP) assay for the detection of SARS-CoV-2 from nasopharyngeal swabs. Methodology. We used a commercial RT-LAMP mastermix from OptiGene in combination with a primer set designed to detect the CDC N1 region of the SARS-CoV-2 nucleocapsid (N) gene. A single-tube, single-step fluorescence assay was implemented whereby 1 µl of universal transport medium (UTM) directly from a nasopharyngeal swab could be used as template, bypassing the requirement for RNA purification. Amplification and detection could be conducted in any thermocycler capable of holding 65 °C for 30 min and measure fluorescence in the FAM channel at 1 min intervals. Results. Assay evaluation by assessment of 157 clinical specimens previously screened by E-gene RT-qPCR revealed assay sensitivity and specificity of 87 and 100%, respectively. Results were fast, with an average time-to-positive (Tp) for 93 clinical s les of 14 min ( sd ±7 min). Using dilutions of SARS-CoV-2 virus spiked into UTM, we also evaluated assay performance against FDA guidelines for implementation of emergency-use diagnostics and established a limit-of-detection of 54 Tissue Culture Infectious Dose 50 per ml (TCID 50 ml −1 ), with satisfactory assay sensitivity and specificity. A comparison of 20 clinical specimens between four laboratories showed excellent interlaboratory concordance performing equally well on three different, commonly used thermocyclers, pointing to the robustness of the assay. Conclusion. With a simplified workflow, The N1 gene Single Tube Optigene LAMP assay (N1-STOP-LAMP) is a powerful, scalable option for specific and rapid detection of SARS-CoV-2 and an additional resource in the diagnostic armamentarium against COVID-19.
Kissing may be an important and neglected risk factor for oropharyngeal gonorrhoea: a cross-sectional study in men who have sex with men
Publisher: BMJ
Date: 09-05-2019
DOI: 10.1136/SEXTRANS-2018-053896
Abstract: A mathematical model suggested that a significant proportion of oropharyngeal gonorrhoea cases are acquired via oropharynx-to-oropharynx transmission (ie, tongue-kissing), but to date, no empirical study has investigated this. This study aimed to examine the association between kissing and oropharyngeal gonorrhoea among gay and bisexual men who have sex with men (MSM). MSM attending a public sexual health centre in Melbourne, Australia, between March 2016 and February 2017 were invited to participate in a brief survey that collected data on their number of male partners in the last 3 months, in three distinct categories: kissing-only (ie, no sex including no oral and/or anal sex), sex-only (ie, any sex without kissing), and kissing-with-sex (ie, kissing with any sex). Univariable and multivariable logistic regression analyses were performed to examine associations between oropharyngeal gonorrhoea positivity by nucleic acid lification tests and the three distinct partner categories. A total of 3677 men completed the survey and were tested for oropharyngeal gonorrhoea. Their median age was 30 (IQR 25–37) and 6.2% (n=229) had oropharyngeal gonorrhoea. Men had a mean number of 4.3 kissing-only, 1.4 sex-only, and 5.0 kissing-with-sex partners in the last 3 months. Kissing-only and kissing-with-sex were associated with oropharyngeal gonorrhoea, but sex-only was not. The adjusted odds for having oropharyngeal gonorrhoea were 1.46-fold (95% CI 1.04 to 2.06) for men with ≥4 kissing-only partners and 1.81-fold (95% CI 1.17 to 2.79) for men with ≥4 kissing-with-sex partners. These data suggest that kissing may be associated with transmission of oropharyngeal gonorrhoea in MSM, irrespective of whether sex also occurs.
New aspirations: The debate on aspiration pneumonia treatment guidelines
Publisher: AMPCo
Date: 10-2011
DOI: 10.5694/MJA11.10298
Abstract: Aspiration pneumonia occurs most commonly in patients with a predisposition to aspiration (eg, those with neurological bulbar dysfunction). There is limited evidence regarding the involvement of anaerobes in most cases of aspiration pneumonia. Most patients respond to treatment for aspiration pneumonia without specific anti-anaerobic therapy such as metronidazole. Metronidazole has adverse side effects, and widespread use where not indicated can promote carriage of multiresistant intestinal flora such as vancomycin-resistant enterococci. Use of metronidazole may be appropriate in patients with aspiration pneumonia and evidence of a lung abscess, necrotising pneumonia, putrid sputum or severe periodontal disease.
The Critical Importance of Sampling Fraction to Inferences of Mycobacterium tuberculosis Transmission
Publisher: Oxford University Press (OUP)
Date: 13-10-2017
DOI: 10.1093/CID/CIX750
Topical Antibiotic Use Coselects for the Carriage of Mobile Genetic Elements Conferring Resistance to Unrelated Antimicrobials in Staphylococcus aureus
Publisher: American Society for Microbiology
Date: 02-2017
DOI: 10.1128/AAC.02000-17
Abstract: Topical antibiotics, such as mupirocin and fusidic acid, are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, the widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains. New Zealand (NZ) has some of the highest globally recorded rates of topical antibiotic usage and resistance. Using a combination of Pacific Biosciences single-molecule real-time (SMRT) whole-genome sequencing, Illumina short-read sequencing, and Bayesian phylogenomic modeling on 118 new multilocus sequence type 1 (ST1) community Staphylococcus aureus isolates from New Zealand and 61 publically available international ST1 genome sequences, we demonstrate a strong correlation between the clinical introduction of topical antibiotics and the emergence of MDR ST1 S. aureus . We also provide in vitro experimental evidence showing that exposure to topical antibiotics can lead to the rapid selection of MDR S. aureus isolates carrying plasmids that confer resistance to multiple unrelated antibiotics, from within a mixed population of competitor strains. These findings have important implications regarding the impact of the indiscriminate use of topical antibiotics.
Obesity and recovery from acute kidney injury (Ob AKI): a prospective cohort feasibility study
Publisher: BMJ
Date: 03-2019
DOI: 10.1136/BMJOPEN-2018-024033
Abstract: To test the methodology of recruitment, retention and data completeness in a prospective cohort recruited after a hospitalised episode of acute kidney injury (AKI), to inform a future prospective cohort study examining the effect of obesity on AKI outcomes. Feasibility study. Single centre, multi-site UK tertiary hospital. 101 participants (67M 34F) with a median age of 64 (IQR 53–73) years, with and without obesity, recruited within 3 months of a hospitalised episode of AKI. Feasibility outcomes were recruitment ( % meeting inclusion criteria recruited), participant retention at 6 and 12 months (≥80%) and completeness of data collection. Exploratory measures included recovery from AKI (regaining % of pre-AKI estimated glomerular filtration rate [eGFR]) at 6 months, development or progression of chronic kidney disease (CKD) (kidney function decrease of ≥25% + rise in CKD category) at 12 months, and associations with poorer kidney outcomes. 41% of eligible patients consented to take part, exceeding the target recruitment uptake rate of 15%. Retention was 86% at 6 months and 78% at 12 months 10 patients died and three commenced dialysis during the study. Data were 90%–100% complete. Median BMI was 27.9 kg/m 2 (range 18.1 kg/m 2 –54.3 kg/m 2 ). 50% of the cohort had stage 3 AKI and 49% had pre-existing CKD. 46% of the cohort met the AKI recovery definition at 6 months. At 12 months, 20/51 patients developed CKD (39%) and CKD progression occurred in 11/49 patients (22%). Post-AKI interleukin-6 and cystatin-C were associated with 12 months decline in eGFR. Feasibility to conduct a long-term observational study addressing AKI outcomes associated with obesity was demonstrated. A fully powered prospective cohort study to examine the relationships between obesity and outcomes of AKI is warranted.
Laparoscopic Sleeve Gastrectomy is a Novel and Effective Treatment for Obesity in Patients with Chronic Kidney Disease
Publisher: Springer Science and Business Media LLC
Date: 25-05-2011
DOI: 10.1007/S11695-011-0448-4
Abstract: Obesity increases the risk of progression of chronic kidney disease (CKD) towards kidney failure and may preclude access to kidney transplantation. Weight loss surgery remains relatively novel in obese patients with CKD, with several studies reporting results using Roux-en-Y bypass and adjustable gastric banding. However, in obese patients with CKD, kidney failure after bypass surgery and gastric band erosion after kidney transplantation have been reported. We present the first report of laparoscopic sleeve gastrectomy (LSG) performed for the treatment of obesity in patients with CKD. Weight loss, blood pressure and lipids, estimated kidney function, surgical complications and adverse events were studied. Nine obese patients with CKD (five of whom were undergoing haemodialysis treatment) underwent LSG, with median body mass index decrease of 8.4 kg/m(2) and excess weight loss of 43.0% after 6 months. Four of the five patients on haemodialysis were added to the kidney transplantation waiting list as a result of weight loss achieved with LSG. Adverse events occurred in three patients: myocardial infarction (one patient), acute kidney injury secondary to dehydration (one patient) and compromised dialysis access (one patient). There was one complication-a gastric leak, detected 7 months after LSG, requiring further surgical intervention and nasojejunal feeding, and no mortality. Our preliminary evidence suggests that LSG is an effective treatment for obesity in patients with CKD. However, there may be additional risk associated with the procedure in patients with CKD, requiring further study.
Daptomycin non-susceptibility in vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous-VISA (hVISA): implications for therapy after vancomycin treatment failure
Publisher: Oxford University Press (OUP)
Date: 02-03-2011
DOI: 10.1093/JAC/DKR066
Abstract: The aim of this study was to establish the relationship between reduced vancomycin and daptomycin susceptibility among Australasian vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous-VISA (hVISA) isolates from patients never exposed to daptomycin. Forty-seven stored clinical isolates of hVISA/VISA collected before November 2008 from around Australia and New Zealand were selected. Daptomycin and vancomycin MIC testing was performed using broth microdilution (BMD) and Etest methods. Daptomycin population analysis was performed on a subset of isolates. The percentage of daptomycin non-susceptible isolates was 0% for vancomycin-susceptible S. aureus (VSSA) (Etest and BMD), for hVISA it was 26% by Etest and 15% by BMD, and for VISA 62% by Etest and 38% by BMD. Population analysis profile testing demonstrated daptomycin heteroresistance among the hVISA and VISA strains tested. This is the highest rate of daptomycin non-susceptibility reported among hVISA isolates to date. Clinicians should exhibit caution when using daptomycin in situations where serious hVISA or VISA infection is a possibility.
Low-level vancomycin resistance in Staphylococcus aureus - An Australian perspective
Publisher: Springer Science and Business Media LLC
Date: 29-01-2005
DOI: 10.1007/S10096-004-1261-Y
Abstract: Low-level vancomycin resistance in Staphylococcus aureus has emerged as a clinical problem over the past 8 years. The clinical relevance of this resistance has been questioned, and laboratory detection remains difficult and time consuming. There is, however, increasing evidence linking low-level vancomycin resistance with glycopeptide treatment failure in serious Staphylococcus aureus infections. Diagnostic laboratories and clinicians need to be aware of this resistance phenotype, to have procedures in place to detect the resistance, and to have strategies for managing patients with infections caused by resistant strains.
A supervised statistical learning approach for accurate Legionella pneumophila source attribution during outbreaks
Publisher: American Society for Microbiology
Date: 11-2017
DOI: 10.1128/AEM.01482-17
Abstract: Public health agencies are increasingly relying on genomics during Legionnaires' disease investigations. However, the causative bacterium ( Legionella pneumophila ) has an unusual population structure, with extreme temporal and spatial genome sequence conservation. Furthermore, Legionnaires' disease outbreaks can be caused by multiple L. pneumophila genotypes in a single source. These factors can confound cluster identification using standard phylogenomic methods. Here, we show that a statistical learning approach based on L. pneumophila core genome single nucleotide polymorphism (SNP) comparisons eliminates ambiguity for defining outbreak clusters and accurately predicts exposure sources for clinical cases. We illustrate the performance of our method by genome comparisons of 234 L. pneumophila isolates obtained from patients and cooling towers in Melbourne, Australia, between 1994 and 2014. This collection included one of the largest reported Legionnaires' disease outbreaks, which involved 125 cases at an aquarium. Using only sequence data from L. pneumophila cooling tower isolates and including all core genome variation, we built a multivariate model using discriminant analysis of principal components (DAPC) to find cooling tower-specific genomic signatures and then used it to predict the origin of clinical isolates. Model assignments were 93% congruent with epidemiological data, including the aquarium Legionnaires' disease outbreak and three other unrelated outbreak investigations. We applied the same approach to a recently described investigation of Legionnaires' disease within a UK hospital and observed a model predictive ability of 86%. We have developed a promising means to breach L. pneumophila genetic ersity extremes and provide objective source attribution data for outbreak investigations. IMPORTANCE Microbial outbreak investigations are moving to a paradigm where whole-genome sequencing and phylogenetic trees are used to support epidemiological investigations. It is critical that outbreak source predictions are accurate, particularly for pathogens, like Legionella pneumophila , which can spread widely and rapidly via cooling system aerosols, causing Legionnaires' disease. Here, by studying hundreds of Legionella pneumophila genomes collected over 21 years around a major Australian city, we uncovered limitations with the phylogenetic approach that could lead to a misidentification of outbreak sources. We implement instead a statistical learning technique that eliminates the ambiguity of inferring disease transmission from phylogenies. Our approach takes geolocation information and core genome variation from environmental L. pneumophila isolates to build statistical models that predict with high confidence the environmental source of clinical L. pneumophila during disease outbreaks. We show the versatility of the technique by applying it to unrelated Legionnaires' disease outbreaks in Australia and the UK.
Systematic analysis of key parameters for genomics-based real-time detection and tracking of multidrug-resistant bacteria
Publisher: Cold Spring Harbor Laboratory
Date: 25-09-2020
DOI: 10.1101/2020.09.24.310821
Abstract: Pairwise single nucleotide polymorphisms (SNPs) are a cornerstone for genomic approaches to multidrug-resistant organisms (MDROs) transmission inference in hospitals. However, the impact of key analysis parameters on these inferences has not been systematically analysed. We conducted a multi-hospital 15-month prospective study, sequencing 1537 MDRO genomes for comparison methicillin-resistant Staphylococcus aureus , vancomycin-resistant Enterococcus faecium , and extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae . We systematically assessed the impact of s le and reference genome ersity, masking of prophage and regions of recombination, cumulative genome analysis compared to a three-month sliding-window, and the comparative effects each of these had when applying a SNP threshold for inferring likely transmission (≤15 SNPs for S. aureus , ≤25 for other species). Across the species, using a reference genome of the same sequence type provided a greater degree of pairwise SNP resolution, compared to species and outgroup-reference alignments that typically resulted in inflated SNP distances and the possibility of missed transmission events. Omitting prophage regions had minimal impacts, however, omitting recombination regions a highly variable effect, often inflating the number of closely related pairs. Estimating pairwise SNP distances was more consistent using a sliding-window than a cumulative approach. The use of a closely-related reference genome, without masking of prophage or recombination regions, and a sliding-window for isolate inclusion is best for accurate and consistent MDRO transmission inference. The increased stability and resolution provided by these approaches means SNP thresholds for putative transmission inference can be more reliably applied among erse MDROs. This work was supported by the Melbourne Genomics Health Alliance (funded by the State Government of Victoria, Department of Health and Human Services, and the ten member organizations) an National Health and Medical Research Council (Australia) Partnership grant (GNT1149991) and in idual grants from National Health and Medical Research Council (Australia) to NLS (GNT1093468), JCK (GNT1008549) and BPH (GNT1105905).
Clinical practice guideline on undernutrition in chronic kidney disease
Publisher: Springer Science and Business Media LLC
Date: 16-10-2019
Altered Protein Composition of Subcutaneous Adipose Tissue in Chronic Kidney Disease
Publisher: Elsevier BV
Date: 11-2017
Genomic surveillance for antimicrobial resistance — a One Health perspective
Publisher: Springer Science and Business Media LLC
Date: 25-09-0012
Evolutionary rate of SARS-CoV-2 increases during zoonotic infection of farmed mink
Publisher: Oxford University Press (OUP)
Date: 2023
DOI: 10.1093/VE/VEAD002
Abstract: To investigate genetic signatures of adaptation to the mink host, we characterised the evolutionary rate heterogeneity in mink-associated severe acute respiratory syndrome coronaviruses (SARS-CoV-2). In 2020, the first detected anthropozoonotic spillover event of SARS-CoV-2 occurred in mink farms throughout Europe and North America. Both spill-back of mink-associated lineages into the human population and the spread into the surrounding wildlife were reported, highlighting the potential formation of a zoonotic reservoir. Our findings suggest that the evolutionary rate of SARS-CoV-2 underwent an episodic increase upon introduction into the mink host before returning to the normal range observed in humans. Furthermore, SARS-CoV-2 lineages could have circulated in the mink population for a month before detection, and during this period, evolutionary rate estimates were between 3 × 10–3 and 1.05 × 10–2 (95 per cent HPD, with a mean rate of 6.59 × 10–3) a four- to thirteen-fold increase compared to that in humans. As there is evidence for unique mutational patterns within mink-associated lineages, we explored the emergence of four mink-specific Spike protein amino acid substitutions Y453F, S1147L, F486L, and Q314K. We found that mutation Y453F emerged early in multiple mink outbreaks and that mutations F486L and Q314K may co-occur. We suggest that SARS-CoV-2 undergoes a brief, but considerable, increase in evolutionary rate in response to greater selective pressures during species jumps, which may lead to the occurrence of mink-specific mutations. These findings emphasise the necessity of ongoing surveillance of zoonotic SARS-CoV-2 infections in the future.
Genomic characterisation reveals a dominant lineage of SARS-CoV-2 in Papua New Guinea
Publisher: Oxford University Press (OUP)
Date: 04-2022
DOI: 10.1093/VE/VEAC033
Abstract: The coronavirus disease pandemic has highlighted the utility of pathogen genomics as a key part of comprehensive public health response to emerging infectious diseases threats, however, the ability to generate, analyse, and respond to pathogen genomic data varies around the world. Papua New Guinea (PNG), which has limited in-country capacity for genomics, has experienced significant outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with initial genomics data indicating a large proportion of cases were from lineages that are not well defined within the current nomenclature. Through a partnership between in-country public health agencies and academic organisations, industry, and a public health genomics reference laboratory in Australia a system for routine SARS-CoV-2 genomics from PNG was established. Here we aim to characterise and describe the genomics of PNG’s second wave and examine the sudden expansion of a lineage that is not well defined but very prevalent in the Western Pacific region. We generated 1797 sequences from cases in PNG and performed phylogenetic and phylodynamic analyses to examine the outbreak and characterise the circulating lineages and clusters present. Our results reveal the rapid expansion of the B.1.466.2 and related lineages within PNG, from multiple introductions into the country. We also highlight the difficulties that unstable lineage assignment causes when using genomics to assist with rapid cluster definitions.
A multi-site, international laboratory study to assess the performance of penicillin susceptibility testing of Staphylococcus aureus
Publisher: Oxford University Press (OUP)
Date: 18-04-2023
DOI: 10.1093/JAC/DKAD116
Abstract: There is clinical uncertainty over the optimal treatment for penicillin-susceptible Staphylococcus aureus (PSSA) infections. Furthermore, there is concern that phenotypic penicillin susceptibility testing methods are not reliably able to detect some blaZ-positive S. aureus. Nine S. aureus isolates, including six genetically erse strains harbouring blaZ, were sent in triplicate to 34 participating laboratories from Australia (n = 14), New Zealand (n = 6), Canada (n = 12), Singapore (n = 1) and Israel (n = 1). We used blaZ PCR as the gold standard to assess susceptibility testing performance of CLSI (P10 disc) and EUCAST (P1 disc) methods. Very major errors (VMEs), major error (MEs) and categorical agreement were calculated. Twenty-two laboratories reported 593 results according to CLSI methodology (P10 disc). Nineteen laboratories reported 513 results according to the EUCAST (P1 disc) method. For CLSI laboratories, the categorical agreement and calculated VME and ME rates were 85% (508/593), 21% (84/396) and 1.5% (3/198), respectively. For EUCAST laboratories, the categorical agreement and calculated VME and ME rates were 93% (475/513), 11% (84/396) and 1% (3/198), respectively. Seven laboratories reported results for both methods, with VME rates of 24% for CLSI and 12% for EUCAST. The EUCAST method with a P1 disc resulted in a lower VME rate compared with the CLSI methods with a P10 disc. These results should be considered in the context that among collections of PSSA isolates, as determined by automated MIC testing, less than 10% harbour blaZ. Furthermore, the clinical relevance of phenotypically susceptible, but blaZ-positive S. aureus, remains unclear.
A review of the public health management of shigellosis in Australia in the era of culture‐independent diagnostic testing
Publisher: Elsevier BV
Date: 12-2016
Abstract: To review the national case definition for shigellosis following the introduction of culture independent diagnostic testing by clinical laboratories and provide evidence to reform jurisdictional public health practices for the management shigellosis., . A review of all Australian jurisdictional public health guidelines for shigellosis was conducted. Victorian 2014 shigellosis data were analysed: demographics and risk factors for cases identified by conventional culture or culture-independent diagnostic methods were described. There was considerable variation in reporting of cases to the National Notifiable Disease Surveillance System (NNDSS) by the eight Australian jurisdictions, with an array of classifications based on diagnostic testing methodologies. Analysis of Victorian 2014 shigellosis data found that culture positive cases were more likely to have reported men who have sex with men (MSM) as a risk factor than PCR positive only cases (p<0.0001) and less likely to have reported overseas travel during their incubation period (p<0.0001). Over a 10-year period (2005 to 2014), only two of 86 cases who were employed in high-risk occupations had ongoing positive faecal cultures after appropriate treatment. The national surveillance case definition for shigellosis should be reviewed to facilitate standardised reporting across Australia. All jurisdictions must consider the public health significance of PCR positive only results in their surveillance risk assessments to inform management of shigellosis cases.
Antiseptic mouthwash against pharyngeal Neisseria gonorrhoeae:A randomised controlled trial and an in vitro study
Publisher: BMJ
Date: 20-12-2017
DOI: 10.1136/SEXTRANS-2016-052753
Abstract: Gonorrhoea is increasing among men who have sex with men (MSM). We aimed to determine whether Listerine, a commercial mouthwash product, has an inhibitory effect against In vitro: a suspension of ∼10 In vitro: Listerine mouthwashes at dilutions of up to 1:4 for 1 min resulted in significant reduction of total This data suggest Listerine, significantly reduces the amount of ACTRN12615000716561.
Solithromycin versus ceftriaxone plus azithromycin for the treatment of uncomplicated genital gonorrhoea (SOLITAIRE-U): a randomised phase 3 non-inferiority trial
Publisher: Elsevier BV
Date: 08-2019
Comparative Study of Selective Chromogenic (chromID VRE) and Bile Esculin Agars for Isolation and Identification of vanB -Containing Vancomycin-Resistant Enterococci fro
Publisher: American Society for Microbiology
Date: 12-2008
DOI: 10.1128/JCM.00944-08
Abstract: The new chromogenic agar chromID VRE (cIDVRE bioMérieux) was compared with bile esculin agar (BD) containing 6 mg/liter vancomycin for the detection of colonization with vanB -containing vancomycin-resistant enterococci (VRE). At 48 h of incubation, the results obtained with both media were comparable. However, cIDVRE detected significantly more VRE at 24 h (39.3% versus 21.3%, P = 0.003), and its use may facilitate the timely implementation of infection control procedures.
Dietitians Australia 2022 – Poster Presentations
Publisher: Wiley
Date: 08-08-2022
Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis
Publisher: Springer Science and Business Media LLC
Date: 03-09-2018
Towards equitable access to public health pathogen genomics in the Western Pacific
Publisher: Elsevier BV
Date: 2022
Genomic interrogation of the burden and transmission of multidrug-resistant pathogens within and across hospital networks
Publisher: Cold Spring Harbor Laboratory
Date: 10-09-2019
DOI: 10.1101/764787
Abstract: Multidrug-resistant organisms (MDROs) disproportionately affect hospitalized patients due to the combination of comorbidities, frequent antimicrobial use, and in-hospital MDRO transmission. Identification of MDRO transmission by hospital microbiology laboratories is difficult due to limitations of existing typing methods. We conducted a prospective multicenter genomics implementation study (8 hospitals, 2800 beds) from 24 th April to 18 th June 2017 in Melbourne, Australia. Clinical and screening isolates from hospital inpatients were collected for six MDROs ( vanA VRE, MRSA, ESBL E. coli [ESBL-Ec] and Klebsiella pneumoniae [ESBL-Kp], and carbapenem-resistant Pseudomonas aeruginosa [CRPa] and Acinetobacter baumannii [CRAb]), sequenced (Illumina NextSeq) and analyzed using open-source tools. MDRO transmission was assessed by genomics (core SNP phylogeny, grouped by species and ST) and compared to epidemiologic data. 408 isolates were collected from 358 patients 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%) and ESBL-Kp (7.6%). We define the transmission rate for each MDRO by genomics and epidemiology 31.6% of all study patients had potential genomic links to other study isolates 86% of these were confirmed by epidemiologic links (probable or possible transmission). The highest transmission rates occurred with van A VRE (88.4% of patients). Combining genomics with high-quality epidemiologic data gives substantial insights into the burden and distribution of critical MDROs in hospitals, including in-hospital transmission. By defining transmission rates by genomics, we hope to enable comparisons over time and between sites, and introduce this as a new outcome measure to assess the efficacy of infection control interventions.
The importance of public health genomics for ensuring health security for Australia
Publisher: AMPCo
Date: 19-03-2019
DOI: 10.5694/MJA2.50063
Functional genomics of Staphylococcus aureus
Publisher: Oxford University Press (OUP)
Date: 21-02-2013
DOI: 10.1093/BFGP/ELT006
Abstract: Staphylococcus aureus remains a major opportunistic human pathogen, and while in many in iduals it is associated with asymptomatic colonization, it is also capable of causing a range of clinical syndromes from minor skin infections to life-threatening septicemia. Staphylococcus aureus has also demonstrated a remarkable capacity to acquire antimicrobial resistance. Recent technological advances in genomics have led to an avalanche of studies providing deep insights into how S. aureus is evolving globally and within the human host. However, there are still significant experimental barriers in using these insights to try and better understand the biology of S. aureus. Here, we summarize recent advances in the understanding of S. aureus through the use of genomic approaches, and contemplate what the near future holds for truly functional genomics that will allow us to better understand the biology of this pathogen.
A Phenotypically Silent vanB2 Operon Carried on a Tn 1549 -Like Element in Clostridium difficile
Publisher: American Society for Microbiology
Date: 31-08-2016
Abstract: In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile . The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile .
Nutrition and Exercise Rehabilitation in Obesity hypoventilation syndrome (NERO): a pilot randomised controlled trial
Publisher: BMJ
Date: 29-09-2017
DOI: 10.1136/THORAXJNL-2016-209826
Abstract: Respiratory management of obesity hypoventilation syndrome (OHS) focusses on the control of sleep-disordered breathing rather than the treatment of obesity. Currently, there are no data from randomised trials of weight loss targeted rehabilitation programmes for patients with OHS. A 3-month multimodal hybrid inpatient–outpatient motivation, exercise and nutrition rehabilitation programme, in addition to non invasive ventilation (NIV), would result in greater per cent weight loss compared with standard care. A single-centre pilot randomised controlled trial allocated patients to either standard care or standard care plus rehabilitation. Primary outcome was per cent weight loss at 12 months with secondary exploratory outcomes of weight loss, exercise capacity and health-related quality of life (HRQOL) at the end of the rehabilitation programme to assess the intervention effect. Thirty-seven patients (11 male, 59.8±12.7 years) with a body mass index of 51.1±7.7 kg/m 2 were randomised. At 12 months, there was no between-group difference in per cent weight loss (mean difference −5.9% (95% CI −14.4% to 2.7% p=0.17)). At 3 months, there was a greater per cent weight loss (mean difference −5% (95% CI −8.3% to −1.4% p=0.007)), increased exercise capacity (6 min walk test 60 m (95% CI 29.5 to 214.5) vs 20 m (95% CI 11.5 to 81.3) p=0.036) and HRQL (mean difference SF-36 general health score (10 (95% CI 5 to 21.3) vs 0 (95% CI −5 to 10) p=0.02)) in the rehabilitation group. In patients with OHS, a 3-month comprehensive rehabilitation programme, in addition to NIV, resulted in improved weight loss, exercise capacity and QOL at the end of the rehabilitation period, but these effects were not demonstrated at 12 months, in part, due to the limited retention of patients at 12 months. Pre-results NCT01483716 .
Population structure, serotype distribution and antibiotic resistance of Streptococcus pneumoniae causing invasive disease in Victoria, Australia.
Publisher: Microbiology Society
Date: 20-07-2023
Abstract: Streptococcus pneumoniae is a major human pathogen and can cause a range of conditions from asymptomatic colonization to invasive pneumococcal disease (IPD). The epidemiology and distribution of IPD-causing serotypes in Australia has undergone large changes following the introduction of the 7-valent pneumococcal conjugate vaccine (PCV) in 2005 and the 13-valent PCV in 2011. In this study, to provide a contemporary understanding of the IPD causing population in Victoria, Australia, we aimed to examine the population structure and prevalence of antimicrobial resistance using whole-genome sequencing and comprehensive antimicrobial susceptibility data of 1288 isolates collected between 2018 and 2022. We observed high ersity among the isolates with 52 serotypes, 203 sequence types (STs) and 70 Global Pneumococcal Sequencing Project Clusters (GPSCs) identified. Serotypes contained in the 13v-PCV represented 35.3 % ( n =405) of isolates. Antimicrobial resistance (AMR) to at least one antibiotic was identified in 23.8 % ( n =358) of isolates with penicillin resistance the most prevalent (20.3 %, n =261 using meningitis breakpoints and 5.1 % n =65 using oral breakpoints). Of the AMR isolates, 28 % ( n =101) were multidrug resistant (MDR) (resistant to three or more drug classes). Vaccination status of cases was determined for a subset of isolates with 34 cases classified as vaccine failure events (fully vaccinated IPD cases of vaccine serotype). However, no phylogenetic association with failure events was observed. Within the highly erse IPD population, we identified six high-risk sub-populations of public health concern characterized by high prevalence, high rates of AMR and MDR, or serotype inclusion in vaccines. High-risk serotypes included serotypes 3, 19F, 19A, 14, 11A, 15A and serofamily 23. In addition, we present our data validating seroBA for in silico serotyping to facilitate ISO-accreditation of this test in routine use in a public health reference laboratory and have made this data set available. This study provides insights into the population dynamics, highlights non-vaccine serotypes of concern that are highly resistant, and provides a genomic framework for the ongoing surveillance of IPD in Australia which can inform next-generation IPD prevention strategies.
Clinical Features Associated with Bacteremia Due to Heterogeneous Vancomycin‐IntermediateStaphylococcus aureus
Publisher: Oxford University Press (OUP)
Date: 02-2004
DOI: 10.1086/381093
Abstract: We assessed all episodes of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia at our hospital during a 12-month period (n=53) and compared those due to heterogeneous vancomycin-intermediate S. aureus (hVISA n = 5, 9.4%) with those due to vancomycin-susceptible MRSA (n=48). Patients with hVISA bacteremia were more likely to have high bacterial load infections (P=.001), vancomycin treatment failure (persistent fever and bacteremia for >7 days after the start of therapy P<.001), and initially low serum vancomycin levels (P=.006). These clinical markers of hVISA bacteremia may help focus diagnostic efforts and treatment.
Co-circulation of Multidrug-resistant Shigella among Men Who Have Sex with Men in Australia
Publisher: Oxford University Press (OUP)
Date: 07-01-2019
DOI: 10.1093/CID/CIZ005
Abstract: In urban Australia, the burden of shigellosis is either in returning travelers from shigellosis-endemic regions or in men who have sex with men (MSM). Here, we combine genomic data with comprehensive epidemiological data on sexual exposure and travel to describe the spread of multidrug-resistant Shigella lineages. A population-level study of all cultured Shigella isolates in the state of Victoria, Australia, was undertaken from 1 January 2016 through 31 March 2018. Antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analyses of 545 Shigella isolates were performed at the Microbiological Diagnostic Unit Public Health Laboratory. Risk factor data on travel and sexual exposure were collected through enhanced surveillance forms or by interviews. Rates of antimicrobial resistance were high, with 17.6% (95/541) and 50.6% (274/541) resistance to ciprofloxacin and azithromycin, respectively. There were strong associations between antimicrobial resistance, phylogeny, and epidemiology. Specifically, 2 major MSM-associated lineages were identified: a Shigellasonnei lineage (n = 159) and a Shigella flexneri 2a lineage (n = 105). Of concern, 147/159 (92.4%) of isolates within the S. sonnei MSM-associated lineage harbored mutations associated with reduced susceptibility to recommended oral antimicrobials: namely, azithromycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Long-read sequencing demonstrated global dissemination of multidrug-resistant plasmids across Shigella species and lineages, but predominantly associated with MSM isolates. Our contemporary data highlight the ongoing public health threat posed by resistant Shigella, both in Australia and globally. Urgent multidisciplinary public health measures are required to interrupt transmission and prevent infection.
Gene expression profiling of astaxanthin and fatty acid pathways in Haematococcus pluvialis in response to different LED lighting conditions
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.BIORTECH.2017.11.094
Abstract: Haematococcus pluvialis is a green microalga of major interest to industry based on its ability to produce large amounts of astaxanthin. Biosynthesis of astaxanthin and its mono- and di-esters was significantly stimulated under 150 μmol m
Evaluation of patient experience post structured education for diabetes self management (Dose Adjustment For Normal Eating-OzDAFNE)
Publisher: Elsevier BV
Date: 11-2021
Cutaneous zygomycosis caused by Saksenaea vasiformis following water-related wound in a 24-year-old immunocompetent woman
Publisher: Wiley
Date: 05-10-2009
DOI: 10.1111/J.1439-0507.2008.01648.X
Abstract: We describe a case of cutaneous zygomycosis caused by Saksenaea vasiformis in an immunocompetent 24-year-old woman. Diagnosis was based on histological and microbiological examination. The patient made a complete recovery with surgical debridement and antifungal therapy (liposomal hotericin and posaconazole).
The nutrition impact symptoms (NIS ) score detects malnutrition risk in patients admitted to nephrology wards
Publisher: Wiley
Date: 26-03-2018
DOI: 10.1111/JHN.12553
Abstract: Nutritional screening tools recommended for the general hospitalised population do not always adequately detect malnutrition risk in patients with kidney disease. The present study assessed the validity and reliability of the Nutrition Impact Symptoms (NIS) score as a nutrition screening tool for hospitalised inpatients prefer in nephrology wards. Nutritional status was classified using Subjective Global Assessment (SGA). NIS scores were calculated from the total score of responses to questions assessing symptoms impacting upon nutritional status from the patient-generated SGA. Concurrent validity of NIS score was assessed using a receiver operating characteristic curve to predict malnutrition risk against SGA. Predictive validity was examined against length of hospital stay (LOS) and 30-day re-admission using Poisson and logistic regression, respectively. Inter-rater reliability of NIS scoring between assessors was determined using intraclass correlation. In 143 patients [90 males mean (SD) age 57.8 (15.8) years], malnutrition prevalence was 38% (54/143) using SGA (rating B/C). Predicting malnutrition risk with an NIS score of ≥3 had a sensitivity of 0.89 and a specificity of 0.65 (area under the curve = 0.81 [95% confidence interval (CI) = 0.74-0.88]). For each 1-point increase in NIS score, the model predicted a 1.9% rise in the risk of an increased LOS (P = 0.002). Thirty-day re-admission was not associated with NIS score. Inter-rater reliability was moderate (mean difference = 0.53 intraclass correlation coefficient = 0.74 95% CI = 0.57-0.85). Nutrition impact symptoms score is a valid stand-alone nutrition screening tool for identifying malnutrition risk in nephrology inpatients and is associated with LOS.
Genomic exploration of sequential clinical isolates reveals a distinctive molecular signature of persistent Staphylococcus aureus bacteraemia.
Publisher: Springer Science and Business Media LLC
Date: 23-08-2018
Tracking the horizontal transfer of plasmids inShigella sonneiandShigella flexneriusing phylogenetics
Publisher: Cold Spring Harbor Laboratory
Date: 28-10-2022
DOI: 10.1101/2022.10.27.514108
Abstract: Antimicrobial resistance (AMR) poses an ever-increasing challenge to the treatment of infections. AMR mechanisms are commonly associated with AMR genes that are carried on mobile elements, such as plasmids that can move between bacterial lineages. Here we introduce an approach that allows us to reconstruct how plasmids move between bacterial lineages. To do so, we model the co-evolution of chromosomal and plasmid DNA in a Bayesian phylogenetic network approach using a joint coalescent and plasmid transfer process. We apply this new approach to a five-year dataset of Shigella isolates from Melbourne, Australia. Doing so, we reconstruct the gain and loss of small plasmids, and the recent dissemination of a multidrug-resistance plasmid between S. sonnei and S. flexneri lineages in multiple independent events and through steady growth in the prevalence since 2010. This approach has a strong potential to improve our understanding of where AMR-carrying plasmids are introduced and maintained.
A new renal inpatient nutrition screening tool (Renal iNUT): a multicenter validation study
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.CLNU.2018.10.002
Abstract: Screening of patients with renal disease for malnutrition risk on hospital admission provides an opportunity to improve prognosis. This study aimed to assess the validity and reliability of the Renal iNUT, a novel renal-specific inpatient nutrition screening tool. Adult inpatient admissions to three renal units were screened using the Renal Inpatient Nutrition Screening Tool (iNUT) and the generic Malnutrition Universal Screening Tool (MUST) and compared against nutritional status using Subjective Global Assessment (SGA) as the standard. Construct validity was assessed by Handgrip Strength (HGS), reliability by repeated iNUT administration and nurse opinion by questionnaire. Of 141 admissions, 45% were malnourished (SGA score B or C). Using iNUT, 49% patients had increased malnutrition risk (score ≥1), 35.5% requiring dietetic referral (score ≥2). MUST indicated 20% at increased malnutrition risk and dietetic referral in 7%. iNUT was more sensitive than MUST in identifying increased malnutrition risk (92.1% vs 44.4%) and dietetic referral (69.8% vs 15.9%). Specificity of iNUT for increased risk was 82.1% and 92.3% for dietetic referral. 47% patients had sarcopenic-range HGS, with significant difference between iNUT score ≥2 and 0 (p < 0.001). iNUT reliability assessed by kappa was 0.74 (95% CI, 0.58 to 0.9), indicating substantial agreement. Nurse evaluation (n = 71) was highly favorable. The Renal iNUT is a valid and reliable nutrition screening tool when used by nurses admitting patients to specialist renal wards. In comparison with MUST, use of iNUT is likely to improve the identification of malnourished patients for nutritional intervention and dietetic referral.
Vancomycin-intermediate Staphylococcus aureus isolates are attenuated for virulence when compared with susceptible progenitors
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.CMI.2017.03.027
Abstract: Vancomycin-intermediate Staphylococcus aureus (VISA) is associated with genetic changes that may also impact upon pathogenicity. In the current study, we compared the virulence of clinical VISA strains with their isogenic vancomycin-susceptible progenitors (VSSA). Production of the critical virulence protein, α toxin, was assessed using Western blot analysis and was correlated to agr activity using a bioluminescent agr-reporter. Cytotoxicity and intracellular persistence were compared ex vivo for VSSA and VISA within non-professional phagocytes (NPP). Virulence and host immune responses were further explored in vivo using a murine model of bacteraemia. VISA isolates produced up to 20-fold less α toxin compared with VSSA, and this was corroborated by either loss of agr activity due to agr mutation, or altered agr activity in the absence of mutation. VISA were less cytotoxic towards NPP and were associated with enhanced intracellular persistence, suggesting that NPP may act as a reservoir for VISA. Infection with VSSA strains produced higher mortality in a murine bacteraemia model (≥90% 7-day mortality) compared with infection with VISA isolates (20% to 50%, p <0.001). Mice infected with VISA produced a d ened immune response (4.6-fold reduction in interleukin-6, p <0.001) and persistent organ bacterial growth was observed for VISA strains out to 7 days. These findings highlight the remarkable adaptability of S. aureus, whereby, in addition to having reduced antibiotic susceptibility, VISA alter the expression of pathogenic factors to circumvent the host immune response to favour persistent infection over acute virulence.
Identification and Mobilization of a Cryptic Antibiotic Biosynthesis Gene Locus from a Human-Pathogenic Nocardia Isolate
Publisher: American Chemical Society (ACS)
Date: 07-11-2019
DOI: 10.1021/ACSCHEMBIO.9B00763
Abstract: The genus
Outbreak of locally acquired azithromycin-resistant Shigella flexneri infection in men who have sex with men
Publisher: Elsevier BV
Date: 2015
Diagnosis and management of Staphylococcus aureus bacteraemia
Publisher: Wiley
Date: 04-11-2005
DOI: 10.1111/J.1444-0903.2005.00977.X
Abstract: Staphylococcus aureus bacteraemia (SAB) is common. Around 8000 cases occur per year in Australia, of which 60% are hospital- or healthcare-associated. Risk factors for SAB include injectable drug use, haemodialysis, indwelling vascular catheters and immunosuppression. Metastatic infection develops in up to one-third of patients with SAB, with joints and heart valves being the most commonly affected sites. Community-acquisition,persistent fever, positive blood cultures after 48 h of treatment and the presence of embolic lesions correlate with the presence of complicated SAB (i.e. high risk of endocarditis and/or other metastatic complications). All patients require careful clinical evaluation to exclude endocarditis and other metastatic foci. Echocardiography,preferably transoesophageal echocardiography, should be performed to exclude endocarditis. Most patients with SAB, and all with features of complicated SAB, require prolonged intravenous antibiotic therapy (at least 4 weeks), but a subgroup with good prognostic features may be suitable for shorter intravenous therapy (2 weeks). Penicillinase-resistant penicillins (e.g.flucloxacillin) are the agents of choice for SAB with methicillin-sensitive strains. Vancomycin or first-generation cephalosporins are alternatives but have lower antimicrobial activity than flucloxacillin. However, vancomycin remains the therapy of choice for SAB due to methicillin-resistant strains. Combination therapy with gentamicin may be useful for the first few days of treatment in selected patients, but otherwise there are few data to support the use of combination regimens in SAB. Newer agents such as linezolid and quinupristin/dalfopristin may have a role in selected patients, especially in SAB due to S. aureus strains with reduced susceptibility to vancomycin.
Microbe-Metabolite Associations Linked to the Rebounding Murine Gut Microbiome Postcolonization with Vancomycin-Resistant Enterococcus faecium
Publisher: American Society for Microbiology
Date: 25-08-2020
DOI: 10.1128/MSYSTEMS.00452-20
Abstract: This study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications.
Hyperexpression of -hemolysin explains enhanced virulence of sequence type 93 community-associated methicillin-resistant Staphylococcus aureus
Publisher: Springer Science and Business Media LLC
Date: 10-02-2014
Effects of vapocoolant spray on skin sterility prior to intravenous cannulation
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.JHIN.2015.03.010
Abstract: Alkane vapocoolant sprays evaporate rapidly, lower skin temperature and result in a temporary interruption in pain sensation. They reduce the pain of intravenous cannulation. However, concern exists that they may recontaminate the sterile cannulation site. To determine the effects of vapocoolant spray on skin sterility prior to cannulation. Fifty patients from the emergency department of a large tertiary metropolitan hospital were enrolled in this study. Bacterial skin swabs were taken from the dorsum of both hands of each patient. From one hand, a swab was taken following standard chlorhexidine disinfection, and a second swab was taken following the application of vapocoolant spray. From the other hand, a swab was taken from unprepared (non-disinfected) skin, and a second swab was taken following vapocoolant application. Skin swabs were sent for microbiological culture and quantitative comparison. The administration of vapocoolant after skin disinfection did not increase the bacterial colony count significantly: median 0.0 [interquartile range (IQR) 0.0] vs 0.0 (IQR 0.0) (P = 0.71). The administration of vapocoolant to the unprepared skin decreased the colony count significantly: median 33.5 (IQR 68) vs 3.0 (IQR 11) (P < 0.001). Alkane vapocoolant spray does not recontaminate the skin after disinfection, and should pose no increased risk of infection when used as an anaesthetic agent prior to intravenous cannulation following disinfection. While it does have inherent bactericidal activity, this is not sufficient for it to be used as the sole disinfectant.
Polyclonal emergence of vanA vancomycin-resistant Enterococcus faecium in Australia
Publisher: Oxford University Press (OUP)
Date: 28-12-2017
DOI: 10.1093/JAC/DKW539
Abstract: To investigate the genetic context associated with the emergence of vanA VRE in Australia. The whole genomes of 18 randomly selected vanA -positive Enterococcus faecium patient isolates, collected between 2011 and 2013 from hospitals in four Australian capitals, were sequenced and analysed. In silico typing and transposon lasmid assembly revealed that the sequenced isolates represented (in most cases) different hospital-adapted STs and were associated with a variety of different Tn 1546 variants and plasmid backbone structures. The recent emergence of vanA VRE in Australia was polyclonal and not associated with the dissemination of a single 'dominant' ST or vanA -encoding plasmid. Interestingly, the factors contributing to this epidemiological change are not known and future studies may need to consider investigation of potential community sources.
Author response: A high-throughput cytotoxicity screening platform reveals agr-independent mutations in bacteraemia-associated Staphylococcus aureus that promote intracellular persistence
Publisher: eLife Sciences Publications, Ltd
Date: 13-04-2023
Rapid Emergence and Evolution of Staphylococcus aureus Clones Harboring fusC -Containing Staphylococcal Cassette Chromosome Elements
Publisher: American Society for Microbiology
Date: 04-2016
DOI: 10.1128/AAC.03020-15
Abstract: The prevalence of fusidic acid (FA) resistance among Staphylococcus aureus strains in New Zealand (NZ) is among the highest reported globally, with a recent study describing a resistance rate of approximately 28%. Three FA-resistant S. aureus clones (ST5 MRSA, ST1 MSSA, and ST1 MRSA) have emerged over the past decade and now predominate in NZ, and in all three clones FA resistance is mediated by the fusC gene. In particular, ST5 MRSA has rapidly become the dominant MRSA clone in NZ, although the origin of FA-resistant ST5 MRSA has not been explored, and the genetic context of fusC in FA-resistant NZ isolates is unknown. To better understand the rapid emergence of FA-resistant S. aureus , we used population-based comparative genomics to characterize a collection of FA-resistant and FA-susceptible isolates from NZ. FA-resistant NZ ST5 MRSA displayed minimal genetic ersity and represented a phylogenetically distinct clade within a global population model of clonal complex 5 (CC5) S. aureus . In all lineages, fusC was invariably located within staphylococcal cassette chromosome (SCC) elements, suggesting that SCC-mediated horizontal transfer is the primary mechanism of fusC dissemination. The genotypic association of fusC with mecA has important implications for the emergence of MRSA clones in populations with high usage of fusidic acid. In addition, we found that fusC was colocated with a recently described virulence factor ( tirS ) in dominant NZ S. aureus clones, suggesting a fitness advantage. This study points to the likely molecular mechanisms responsible for the successful emergence and spread of FA-resistant S. aureus .
Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from 13,000SalmonellaTyphi genomes
Publisher: Cold Spring Harbor Laboratory
Date: 30-12-2022
DOI: 10.1101/2022.12.28.22283969
Abstract: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks twenty-one years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000), and provides a detailed overview of global genotype and antimicrobial resistance (AMR) distribution and temporal trends, generated using open analysis platforms (GenoTyphi and Pathogenwatch). Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show potential of travel-associated data to provide informal “sentinel” surveillance for such locations. The data indicate ciprofloxacin non-susceptibility ( resistance determinant) is widespread across geographies and genotypes, with high-level resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020), but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. The Consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies.
Complete microbial genomes for public health in Australia and the Southwest Pacific
Publisher: Microbiology Society
Date: 12-2020
Abstract: Complete genomes of microbial pathogens are essential for the phylogenomic analyses that increasingly underpin core public health laboratory activities. Here, we announce a BioProject (PRJNA556438) dedicated to sharing complete genomes chosen to represent a range of pathogenic bacteria with regional importance to Australia and the Southwest Pacific enriching the catalogue of globally available complete genomes for public health while providing valuable strains to regional public health microbiology laboratories. In this first step, we present 26 complete high-quality bacterial genomes. Additionally, we describe here a framework for reconstructing complete microbial genomes and highlight some of the challenges and considerations for accurate and reproducible genome reconstruction.
Short-term increase in the carriage of azithromycin-resistant Escherichia coli and Klebsiella pneumoniae in mothers and their newborns following intra-partum azithromycin: a post hoc ana
Publisher: Oxford University Press (OUP)
Date: 18-01-2021
Abstract: To evaluate the impact of one oral dose of intrapartum azithromycin (2 g) on the carriage and antibiotic resistance of Escherichia coli and Klebsiella pneumoniae in the nasopharynx, breast milk and vaginal swabs of mothers and K. pneumoniae in the nasopharynx of their newborns. We performed a post hoc analysis of a double-blind, placebo-controlled randomized-trial (ratio 1:1) conducted in The Gambia. Breast milk (BM) and vaginal swabs (VS) from mothers and nasopharyngeal swabs (NPS) from mother–newborn pairs were collected at different timepoints during the 4 week follow-up. S les were processed using standard microbiological procedures. For BM and NPS post-intervention results were combined for analysis. In the original trial 829 mothers were randomized. In this analysis, complete s le sets were available for 630 mothers for E. coli analysis (76.0%) and 564 mother–newborn pairs for K. pneumoniae analysis (68.0%). For E. coli, carriage prevalence in BM and VS was similar in both arms but resistance was higher in the azithromycin arm in VS (2.6% versus 0%, P = 0.004). For K. pneumoniae, carriage prevalence was higher in the azithromycin arm for BM (13.8% versus 8.7%, P = 0.055) but not for VS or NPS. Prevalence of azithromycin resistant K. pneumoniae was higher in the azithromycin arm for BM (3.6% versus 1.0%, P = 0.050) and VS (1.5% versus 0% P = 0.057). Oral intrapartum azithromycin did not reduce carriage of E. coli and K. pneumoniae and was associated with an increase in the prevalence of azithromycin-resistant E. coli and K. pneumoniae isolates in BM and VS.
Complete microbial genomes for public health in Australia and Southwest Pacific
Publisher: Cold Spring Harbor Laboratory
Date: 05-11-2019
DOI: 10.1101/829663
Abstract: Complete genomes of microbial pathogens are essential for the phylogenomic analyses that increasingly underpin core public health lab activities. Here, we present complete genomes of pathogen strains of regional importance to the Southwest Pacific and Australia. These enrich the catalogue of globally available complete genomes for public health while providing valuable strains to regional public health labs. Whole-genome sequence (WGS) data is increasingly important in public health microbiology (1–4). The data can be used to replicate many of the basic bacterial sub-typing approaches, as well as support epidemiological investigations, such as surveillance and outbreak investigation (5–7). The appeal of WGS data comes from the promise of a single workflow to process all microbial pathogens that can provide easily portable data that promotes deeper integration of surveillance and investigation efforts across jurisdictions. This promise is leading to a concerted effort to move microbial public health to a primarily genome-based workflow at numerous jurisdictions (8–10), including Australia (11).
New rules for genomics-informed COVID-19 responses–Lessons learned from the first waves of the Omicron variant in Australia
Publisher: Public Library of Science (PLoS)
Date: 13-10-2022
Staphylococcus aureus small colony variants impair host immunity by activating host cell glycolysis and inducing necroptosis.
Publisher: Springer Science and Business Media LLC
Date: 04-11-2020
DOI: 10.1038/S41564-019-0597-0
Abstract: Staphylococcus aureus small colony variants (SCVs) are frequently associated with chronic infection, yet they lack expression of many virulence determinants associated with the pathogenicity of wild-type strains. We found that both wild-type S. aureus and a ΔhemB SCV prototype potently activate glycolysis in host cells. Glycolysis and the generation of mitochondrial reactive oxygen species were sufficient to induce necroptosis, a caspase-independent mechanism of host cell death that failed to eradicate S. aureus and instead promoted ΔhemB SCV pathogenicity. To support ongoing glycolytic activity, the ΔhemB SCV induced over a 100-fold increase in the expression of fumC, which encodes an enzyme that catalyses the degradatin of fumarate, an inhibitor of glycolysis. Consistent with fumC-dependent depletion of local fumarate, the ΔhemB SCV failed to elicit trained immunity and protection from a secondary infectious challenge in the skin. The reliance of the S. aureus SCV population on glycolysis accounts for much of its role in the pathogenesis of S. aureus skin infection.
The interface between antibiotic resistance and virulence in staphylococcus aureus and its impact upon clinical outcomes
Publisher: Oxford University Press (OUP)
Date: 24-08-2011
DOI: 10.1093/CID/CIR473
Abstract: The ability of Staphylococcus aureus to rapidly acquire antibiotic resistance in the face of antimicrobial challenge has enabled it to remain an ongoing, significant human pathogen. Mechanisms behind the evolution of resistance in S. aureus are well documented, but the effects of these phenotypes upon virulence are less clear. By exploring available clinical and experimental data, we have shown that a number of the major steps in the evolution of antibacterial resistance in S. aureus have been accompanied by alterations in virulence. This review also highlights that further experimentation is required to fully elucidate the mechanisms involved in the interface between virulence and antibiotic resistance, with the intention of identifying novel preventative or therapeutic strategies for this important human pathogen.
Asymptomatic and symptomatic urethral gonorrhoea in men who have sex with men attending a sexual health service
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.CMI.2017.02.020
Abstract: Guidelines regarding whether men who have sex with men (MSM) without symptoms of urethritis should be screened for urethral gonorrhoea differ between countries. We examined the rate of asymptomatic urethral gonorrhoea in MSM using sensitive nucleic acid lification testing. This study was conducted on consecutive MSM attending the Melbourne Sexual Health Centre between July 2015 and May 2016 for sexually transmitted infections screening. Gonorrhoea testing with the Aptima Combo 2 (AC2) assay was performed on all urine specimens obtained from MSM, whether symptoms of urethritis were present or not. Men were classified as having: typical discharge if they reported symptoms suggesting purulent discharge other symptoms if they reported other symptoms of urethritis and no symptoms if they reported no urethral symptoms. During the study period, there were 7941 clinic visits by 5947 in idual MSM with 7090 urine specimens obtained from 5497 in idual MSM tested with the AC2 assay. Urethral gonorrhoea was detected in 242 urine specimens from 228 in idual MSM. The majority (189/242, 78%, 95% CI 73-83) reported typical discharge, 27/242 (11%, 95% CI 8-16) reported other urethral symptoms, and 26/242 (11%, 95% CI 7-15) reported no symptoms on the day of presentation and testing. Among men with urethral gonorrhoea, the proportions with concurrent pharyngeal or rectal gonorrhoea were 32% (134/210) and 64% (74/235), respectively. The mean interval between last reported sexual contact and onset of typical urethral discharge, where present, was 3.9 days. The findings from our study lend support to guidelines that recommend screening asymptomatic MSM for urethral gonorrhoea.
Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: A cross-sectional study
Publisher: Elsevier BV
Date: 08-2015
Community case management of childhood illnesses: policy and implementation in Countdown to 2015 countries
Publisher: WHO Press
Date: 03-2012
Pandemic printing: a novel 3D‐printed swab for detecting SARS ‐CoV‐2
Publisher: AMPCo
Date: 09-08-2020
DOI: 10.5694/MJA2.50726
Structure–Activity Relationships of Daptomycin Lipopeptides
Publisher: American Chemical Society (ACS)
Date: 20-07-2020
Whole-genome sequencing reveals transmission of gonococcal antibiotic resistance among men who have sex with men: An observational study
Publisher: BMJ
Date: 15-12-2018
DOI: 10.1136/SEXTRANS-2017-053287
Abstract: Drug-resistant Neisseria gonorrhoeae are now a global public health threat. Direct transmission of antibiotic-resistant gonococci between in iduals has been proposed as a driver for the increased transmission of resistance, but direct evidence of such transmission is limited. Whole-genome sequencing (WGS) has superior resolution to investigate outbreaks and disease transmission compared with traditional molecular typing methods such as multilocus sequence typing (MLST) and N. gonorrhoeae multiantigen sequence (NG-MAST). We therefore aimed to systematically investigate the transmission of N. gonorrhoeae between men in sexual partnerships using WGS to compare isolates and their resistance to antibiotics at a genome level. 458 couples from a large prospective cohort of men who have sex with men (MSM) tested for gonorrhoea together between 2005 and 2014 were included, and WGS was conducted on all isolates from couples where both men were culture-positive for N. gonorrhoeae . Resistance-determining sequences were identified from genome assemblies, and comparison of isolates between and within in iduals was performed by pairwise single nucleotide polymorphism and pangenome comparisons, and in silico predictions of NG-MAST and MLST. For 33 of 34 (97% 95% CI 85% to 100%) couples where both partners were positive for gonorrhoea, the resistance-determining genes and mutations were identical in isolates from each partner (94 isolates in total). Resistance determinants in isolates from 23 of 23 (100% 95% CI 86% to 100%) men with multisite infections were also identical within an in idual. These partner and within-host isolates were indistinguishable by NG-MAST, MLST and whole genomic comparisons. These data support the transmission of antibiotic-resistant strains between sexual partners as a key driver of resistance rates in gonorrhoea among MSM. This improved understanding of the transmission dynamics of N. gonorrhoeae between sexual partners will inform treatment and prevention guidelines.
Serine/threonine phosphatase stp1 contributes to reduced susceptibility to vancomycin and virulence in staphylococcus aureus
Publisher: Oxford University Press (OUP)
Date: 05-04-2012
An open-label, parallel-group, randomised controlled trial of antiseptic mouthwash versus antibiotics for oropharyngeal gonorrhoea treatment (OMEGA2)
Publisher: Springer Science and Business Media LLC
Date: 09-11-2020
DOI: 10.1038/S41598-020-76184-1
Abstract: New treatments for oropharyngeal gonorrhoea are required to address rising antimicrobial resistance. We aimed to examine the efficacy of a 14-day course of mouthwash twice daily compared to standard treatment (antibiotic) for the treatment of oropharyngeal gonorrhoea. The OMEGA2 trial was a parallel-group and open-labelled randomised controlled trial among men with untreated oropharyngeal gonorrhoea that was conducted between September 2018 and February 2020 at Melbourne Sexual Health Centre in Australia. Men were randomised to the intervention (rinsing, gargling and spraying mouthwash twice daily for 14 days) or control (standard treatment) arm and followed for 28 days. Participants in both arms were advised to abstain from sex and kissing with anyone for 14 days after enrolment. Oropharyngeal swabs were collected at baseline, Day 14 and Day 28 and tested for Neisseria gonorrhoeae by nucleic acid lification test (NAAT) and culture. The primary outcome was the detection of oropharyngeal N. gonorrhoeae by NAAT at Day 14 after treatment. This trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12618001380280). This trial stopped early due to a high failure rate in the mouthwash arm. Twelve men were randomly assigned to either mouthwash (n = 6) or standard treatment (n = 6). Of the 11 men who returned at Day 14, the cure rate for oropharyngeal gonorrhoea in the mouthwash arm was 20% (95% CI 1–72% 1/5) and in the standard treatment arm was 100% (95% CI 54–100% 6/6). A 14-day course of mouthwash failed to cure a high proportion of oropharyngeal gonorrhoea cases.
Significant variability exists in the cytotoxicity of global methicillin-resistant Staphylococcus aureus lineages
Publisher: Microbiology Society
Date: 20-12-2021
DOI: 10.1099/MIC.0.001119
Abstract: Staphylococcus aureus is a major human pathogen where the emergence of antibiotic resistant lineages, such as methicillin-resistant S. aureus (MRSA), is a major health concern. While some MRSA lineages are restricted to the healthcare setting, the epidemiology of MRSA is changing globally, with the rise of specific lineages causing disease in healthy people in the community. In the past two decades, community-associated MRSA (CA-MRSA) has emerged as a clinically important and virulent pathogen associated with serious skin and soft-tissue infections (SSTI). These infections are primarily cytotoxin driven, leading to the suggestion that hypervirulent lineages/multi-locus sequence types (STs) exist. To examine this, we compared the cytotoxicity of 475 MRSA isolates representing five major MRSA STs (ST22, ST93, ST8, ST239 and ST36) by employing a monocyte-macrophage THP-1 cell line as a surrogate for measuring gross cytotoxicity. We demonstrate that while certain MRSA STs contain highly toxic isolates, there is such variability within lineages to suggest that this aspect of virulence should not be inferred from the genotype of any given isolate. Furthermore, by interrogating the accessory gene regulator (Agr) sequences in this collection we identified several Agr mutations that were associated with reduced cytotoxicity. Interestingly, the majority of isolates that were attenuated in cytotoxin production contained no mutations in the agr locus, indicating a role of other undefined genes in S. aureus toxin regulation.
Effect of Exercise Training on Estimated GFR, Vascular Health, and Cardiorespiratory Fitness in Patients With CKD: A Pilot Randomized Controlled Trial
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1053/J.AJKD.2014.07.015
Abstract: Exercise capacity, which is predictive of all-cause mortality and cardiovascular disease risk, is reduced significantly in patients with non-dialysis-dependent chronic kidney disease. This pilot study examined the effect of moderate-intensity exercise training on kidney function and indexes of cardiovascular risk in patients with progressive chronic kidney disease stages 3 to 4. Single-blind, randomized, controlled, parallel trial. 20 patients (aged 18-80 years 17 men) randomly assigned to rehabilitation (n=10) or usual care (n=10). Participants were included if they were 18 years or older and had evidence of rate of decline in creatinine-based estimated glomerular filtration rate (eGFRcr)≥2.9mL/min/1.73m(2) per year for 12 months preintervention. Patients were excluded if they had unstable medical conditions or had recently started regular exercise. The rehabilitation group received resistance and aerobic training (3 days per week) for a 12-month period. The usual care group received standard care. Kidney function assessed by comparing mean rate of change in eGFRcr (mL/min/1.73m(2) per year) from a 12-month preintervention period against the 12-month intervention period. Pulse wave velocity (PWV), peak oxygen uptake (Vo2peak), and waist circumference assessed at 0, 6, and 12 months. eGFR assessed using creatinine, cystatin C (eGFRcys), and a combination of both values (eGFRcr-cys). 18 participants (rehabilitation, 8 usual care, 10) completed the study. A significant mean difference in rate of change in eGFRcr (+7.8±3.0 [95% CI, 1.1-13.5] mL/min/1.73m(2) per year P=0.02) was observed between the rehabilitation and usual care groups, with the rehabilitation group demonstrating a slower decline. No significant between-group mean differences existed in absolute eGFRcr, eGFRcr-cys, or eGFRcys at 12 months of study intervention. Significant between-group mean differences existed in PWV (-2.30 [95% CI, -3.02 to -1.59] m/s), waist circumference (-7.1±12.8 [95% CI, -12.4 to -3.2] cm), and Vo2peak (5.7 [95% CI, 1.34-10.10] mL/kg/min). Change in eGFRcr was correlated inversely with PWV (r=-0.5 P=0.04) at 12 months. Small s le size, inconsistency between primary and secondary measures of kidney function. The effect of a 1-year exercise intervention on progression of kidney disease is inconclusive. A larger study with longer follow-up may be necessary.
Managing a nosocomial outbreak of carbapenem-resistant Klebsiella pneumoniae: An early Australian hospital experience
Publisher: Wiley
Date: 10-2015
DOI: 10.1111/IMJ.12863
Abstract: Carbapenems are traditionally reserved as the last line of defence for treatment of serious infections with multiresistant Gram-negative bacilli. Reports of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms have been emerging globally, but rare in Australasia to date. We describe an outbreak of KPC-2 producing K. pneumoniae at an Australian hospital. After initial detection in October 2012, a retrospective review of patients with meropenem-resistant K. pneumoniae to June 2012, and ongoing prospective surveillance, was undertaken. Included patients were admitted to the hospital after June 2012 and had meropenem-resistant K. pneumoniae isolated from any site. Available isolates underwent detection of the KPC-2 gene by polymerase chain reaction and molecular typing was performed to determine genetic relatedness between isolates. Point-prevalence screening was performed on selected wards to detect asymptomatic carriage. Infection control procedures were implemented to contain the outbreak. Ten cases were identified in the initial cluster. Eight were localised to a single inpatient ward. Point-prevalence screening revealed one extra case. After temporary containment, re-emergence of KPC-producing isolates was observed post October 2013 with 18 further cases identified. Four K. pneumoniae isolates in the 2012 cluster and 16 from the 2013-2014 cluster were referred for further testing. All carried the KPC-2 beta-lactamase gene. The 2012 isolates were genetically similar to the 2014 isolates. KPC-2 mediated resistance is an emerging threat in Australia. The re-emergence of KPC despite initial containment emphasises the need for constant vigilance in the microbiology laboratory and ongoing maintenance of infection control and antimicrobial stewardship activity.
Outbreak investigation using high-throughput genome sequencing within a diagnostic microbiology laboratory
Publisher: American Society for Microbiology
Date: 05-2013
DOI: 10.1128/JCM.03332-12
Abstract: Next-generation sequencing (NGS) of bacterial genomes has recently become more accessible and is now available to the routine diagnostic microbiology laboratory. However, questions remain regarding its feasibility, particularly with respect to data analysis in nonspecialist centers. To test the applicability of NGS to outbreak investigations, Ion Torrent sequencing was used to investigate a putative multidrug-resistant Escherichia coli outbreak in the neonatal unit of the Mercy Hospital for Women, Melbourne, Australia. Four suspected outbreak strains and a comparator strain were sequenced. Genome-wide single nucleotide polymorphism (SNP) analysis demonstrated that the four neonatal intensive care unit (NICU) strains were identical and easily differentiated from the comparator strain. Genome sequence data also determined that the NICU strains belonged to multilocus sequence type 131 and carried the bla CTX-M-15 extended-spectrum beta-lactamase. Comparison of the outbreak strains to all publicly available complete E. coli genome sequences showed that they clustered with neonatal meningitis and uropathogenic isolates. The turnaround time from a positive culture to the completion of sequencing (prior to data analysis) was 5 days, and the cost was approximately $300 per strain (for the reagents only). The main obstacles to a mainstream adoption of NGS technologies in diagnostic microbiology laboratories are currently cost (although this is decreasing), a paucity of user-friendly and clinically focused bioinformatics platforms, and a lack of genomics expertise outside the research environment. Despite these hurdles, NGS technologies provide unparalleled high-resolution genotyping in a short time frame and are likely to be widely implemented in the field of diagnostic microbiology in the next few years, particularly for epidemiological investigations (replacing current typing methods) and the characterization of resistance determinants. Clinical microbiologists need to familiarize themselves with these technologies and their applications.
B ritish Dietetic Association evidence‐based guidelines for the protein requirements of adults undergoing maintenance haemodialysis or peritoneal dialysis
Publisher: Wiley
Date: 04-06-2013
DOI: 10.1111/JHN.12052
Abstract: Existing nutritional guidelines suggest that protein requirements of adults with stage five chronic kidney disease undergoing haemodialysis (HD) or peritoneal dialysis (PD) are increased as a result of protein losses during dialysis. The present review aimed to update previous guidance and develop evidence-based practice guidelines on the protein requirements of adults undergoing maintenance dialysis. Following a PICO approach (Participants or Population, Intervention or Exposure, Comparison and Outcome), four research questions were formulated to investigate the total protein requirement and protein quality required by adults undergoing HD and PD. A comprehensive, systematic review was undertaken using the databases Medline, EMBASE and the Cochrane Library from 2005 to September 2009 for HD studies and from 1997 to September 2009 for PD studies. The literature search yielded 2931 studies, which were assessed for inclusion. Following appraisal, 19 studies in HD and 18 studies in PD met the inclusion criteria and were systematically reviewed. Limited good quality evidence supports the recommendations that: (i) adults undergoing maintenance HD require a minimum protein intake of 1.1 g kg(-1) ideal body weight (IBW) per day and (ii) adults undergoing maintenance PD require a minimum protein intake of 1.0-1.2 kg(-1) IBW per day, in conjunction with an adequate energy intake. There were no studies that addressed the quality of protein for either HD or PD. Evidence suggests that nutritional status may be maintained with lower protein intakes than previously recommended. However, the evidence base is limited and further randomised controlled trials are required to establish the optimal protein intake for dialysis patients.
Sharing Is Caring: International Sharing of Data Enhances Genomic Surveillance of Listeria monocytogenes
Publisher: Oxford University Press (OUP)
Date: 09-06-2016
DOI: 10.1093/CID/CIW359
Biosynthesis and Ether‐Bridge Formation in Nargenicin Macrolides
Publisher: Wiley
Date: 11-02-2019
Investigation of trimethoprim/sulfamethoxazole resistance in an emerging sequence type 5 methicillin-resistant Staphylococcus aureus clone reveals discrepant resistance reporting
Publisher: Elsevier BV
Date: 09-2018
Genomic analysis of teicoplanin resistance emerging during treatment of vanB vancomycin-resistant Enterococcus faecium infections in solid organ transplant recipients including donor-derived cases
Publisher: Oxford University Press (OUP)
Date: 23-04-2013
DOI: 10.1093/JAC/DKT130
Abstract: We noted four cases of apparent in vivo emergence of teicoplanin resistance during failed therapy for initially teicoplanin-susceptible vanB vancomycin-resistant Enterococcus faecium (VREfm) infections in solid organ transplant recipients at our institution over a 12 month period. We investigated if in vivo emergence of resistance had occurred, if transplant-related vancomycin-resistant Enterococcus (VRE) infections had occurred and identified clinical predictors of resistance emergence. Whole genome sequencing was performed on nine VREfm isolates for phylogenetic analysis and to identify determinants of teicoplanin resistance. Clinical treatment details were compared with other patients who received teicoplanin for confirmed vanB VRE infections but did not develop resistance during the same year at our institution. A high-resolution, core genome phylogeny was inferred for nine VREfm isolates and confirmed in vivo development of resistance during failed therapy in four cases. Four different non-synonymous single nucleotide polymorphisms (SNPs) were observed in the vanRS genes of teicoplanin-resistant strains compared with the index teicoplanin-susceptible strains, and these SNPs were predicted to confer teicoplanin resistance. VREfm within a cluster of early transplant-related infections were phylogenetically identical at the core genome level, indicating a common source donor. Focus eradication and absence of prosthetic material were characteristics of those patients treated successfully. Clinicians should be cautious of resistance emerging during teicoplanin therapy for vanB VRE, particularly in immunosuppressed patients or where source control is difficult.
Viral Genomics to Inform Infection-control Response in Occupational Coronavirus Disease 2019 (COVID-19) Transmission
Publisher: Oxford University Press (OUP)
Date: 14-09-2020
DOI: 10.1093/CID/CIAA1385
Abstract: Healthcare workers are at increased risk of occupational transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report 2 instances of healthcare workers contracting SARS-CoV-2 despite no known breach of personal protective equipment. Additional specific equipment cleaning was initiated. Viral genomic sequencing supported this transmission hypothesis and our subsequent response.
Different bacterial gene expression patterns and attenuated host immune responses are associated with the evolution of low-level vancomycin resistance during persistent methicillin-resistant Staphylococcus aureus bacteraemia
Publisher: Springer Science and Business Media LLC
Date: 2008
Vancomycin Exposure and Acute Kidney Injury Outcome: A Snapshot From the CAMERA2 Study
Publisher: Oxford University Press (OUP)
Date: 04-11-2020
DOI: 10.1093/OFID/OFAA538
Abstract: Among patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia from a prospective randomized clinical trial, acute kidney injury (AKI) rates increased with increasing vancomycin exposure, even within the therapeutic range. AKI was independently more common for the (flu)cloxacillin group. Day 2 vancomycin AUC ≥470 mg·h/L was significantly associated with AKI, independent of (flu)cloxacillin receipt.
Vancomycin minimum inhibitory concentration, host comorbidities and mortality in staphylococcus aureus bacteraemia
Publisher: Elsevier BV
Date: 12-2013
Antibiotic Choice May Not Explain Poorer Outcomes in Patients With Staphylococcus aureus Bacteremia and High Vancomycin Minimum Inhibitory Concentrations
Publisher: Oxford University Press (OUP)
Date: 08-2011
Abstract: There are concerns about reduced efficacy of vancomycin in patients with Staphylococcus aureus bacteremia (SAB), especially when the minimum inhibitory concentration (MIC) nears the upper limit of the susceptible range. We examined the relationship between antibiotic treatment, 30-day mortality, and microbiologic parameters in a large Australasian cohort of patients with SAB. We assessed 532 patients with SAB from 8 hospitals. All patients with methicillin-resistant S. aureus (MRSA) bacteremia were treated with vancomycin, and patients with methicillin-susceptible S. aureus (MSSA) bacteremia received either flucloxacillin or vancomycin. Increasing vancomycin MIC was associated with increased mortality in vancomycin-treated patients. However, even in patients with MSSA bacteremia treated with flucloxacillin, mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5 μg/mL, compared with those with lower MIC isolates (26.8% vs 12.2% P < .001). After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin MIC were independently associated with mortality, but methicillin resistance and antibiotic choice were not. We have confirmed an association between higher vancomycin MIC and increased mortality in patients with SAB, but surprisingly this relationship was not related to the antibiotic treatment received, suggesting that the use of vancomycin per se is not responsible for the poorer outcome.
Molecular characterization and antimicrobial susceptibilities of Clostridium difficile clinical isolates from Victoria, Australia
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.ANAEROBE.2015.05.001
Abstract: Some Australian strain types of Clostridium difficile appear unique, highlighting the global ersity of this bacterium. We examined recent and historic local isolates, finding predominantly toxinotype 0 strains, but also toxinotypes V and VIII. All isolates tested were susceptible to vancomycin and metronidazole, while moxifloxacin resistance was only detected in recent strains.
Interventions for weight loss in people with chronic kidney disease who are overweight or obese
Publisher: Wiley
Date: 06-09-2018
Genomic Insights Into Last-Line Antimicrobial Resistance in Multidrug-Resistant Staphylococcus and Vancomycin-Resistant Enterococcus
Publisher: Frontiers Media SA
Date: 16-03-2021
DOI: 10.3389/FMICB.2021.637656
Abstract: Multidrug-resistant Staphylococcus and vancomycin-resistant Enterococcus (VRE) are important human pathogens that are resistant to most clinical antibiotics. Treatment options are limited and often require the use of ‘last-line’ antimicrobials such as linezolid, daptomycin, and in the case of Staphylococcus , also vancomycin. The emergence of resistance to these last-line antimicrobial agents is therefore of considerable clinical concern. This mini-review provides an overview of resistance to last-line antimicrobial agents in Staphylococcus and VRE, with a particular focus on how genomics has provided critical insights into the emergence of resistant clones, the molecular mechanisms of resistance, and the importance of mobile genetic elements in the global spread of resistance to linezolid.
Assessing the fertilizing potential of microalgal digestates using the marine diatom Chaetoceros muelleri
Publisher: Elsevier BV
Date: 08-2019
Risk prediction for acute kidney injury in acute medical admissions in the UK
Publisher: Oxford University Press (OUP)
Date: 28-11-2018
DOI: 10.1093/QJMED/HCY277
Abstract: Acute Kidney Injury (AKI) is associated with adverse outcomes therefore identifying patients who are at risk of developing AKI in hospital may lead to targeted prevention. We undertook a UK-wide study in acute medical units (AMUs) to define those who develop hospital-acquired AKI (hAKI) to determine risk factors associated with hAKI and to assess the feasibility of developing a risk prediction score. Prospective multi-centre cohort study across 72 AMUs in the UK. Data collected from all patients who presented over a 24-h period. Chronic dialysis, community-acquired AKI (cAKI) and those with fewer than two creatinine measurements were excluded. Primary outcome was the development of h-AKI. Two thousand four hundred and fourty-six in iduals were admitted to the seventy-two participating centres. Three hundred and eighty-four patients (16%) sustained AKI of whom two hundred and eighty-seven (75%) were cAKI and ninety-seven (25%) were hAKI. After exclusions, chronic kidney disease [Odds Ratio (OR) 3.08, 95% Confidence Interval (CI) 1.96-4.83], diuretic prescription (OR 2.33, 95% CI 1.5-3.65), a lower haemoglobin concentration and elevated serum bilirubin were independently associated with development of hAKI. Multi-variable model discrimination was only moderate (c-statistic 0.75). AKI in AMUs is common and associated with worse outcomes, with the majority of cases community acquired. Only a small proportion of patients develop hAKI. Prognostic risk factor modelling demonstrated only moderate discrimination implying that widespread adoption of such an AKI clinical risk score across all AMU admissions is not currently justified. More targeted risk assessment or automated methods of calculating in idual risk may be more appropriate alternatives.
Global disparities in SARS-CoV-2 genomic surveillance
Publisher: Cold Spring Harbor Laboratory
Date: 26-08-2021
DOI: 10.1101/2021.08.21.21262393
Abstract: Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes days after s le collection, and 77% of low and middle income countries sequenced .5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness. Socioeconomic inequalities impacted the SARS-CoV-2 genomic surveillance, and undermined the global pandemic preparedness.
Long-term Impact of Pneumococcal Conjugate Vaccines on Invasive Disease and Pneumonia Hospitalizations in Indigenous and Non-Indigenous Australians
Publisher: Oxford University Press (OUP)
Date: 07-08-2019
DOI: 10.1093/CID/CIZ731
Abstract: Universal pneumococcal conjugate vaccine (PCV) programs began in Indigenous Australian children in 2001 and all children in 2005, changing to 13-valent PCV (PCV13) in 2011. We used laboratory data for invasive pneumococcal disease (IPD) and coded hospitalizations for noninvasive pneumococcal community-acquired pneumonia (PnCAP) to evaluate long-term impact. Annual incidence (per 100 000 population) was calculated for age-specific total IPD, PCV13 non–7-valent PCV (PCV7) serotypes, and PnCAP by Indigenous status. Incidence in the pre–universal PCV7 (2002–2004), early PCV7 (2005–2007), pre-PCV13 (2008 to mid-2011), and post-PCV13 (mid-2011 to 2016) periods was used to calculate incidence rate ratios (IRRs). In the total population, all-age incidence of IPD declined from 11.8 pre-PCV7 to 7.1 post-PCV13 (IRR, 0.61 [95% confidence interval {CI}, .59–.63]) but for PnCAP declined among ages & year (IRR, 0.34 [95% CI, .25–.45]) and 1–4 years (IRR, 0.50 [95% CI, .43–.57]) but increased significantly among age ≥5 years (IRRs, 1.08–1.14). In Indigenous people, baseline PCV13 non-PCV7 IPD incidence was 3-fold higher, lified by a serotype 1 epidemic in 2011. By 2015–2016, although incidence of IPD and PnCAP in children aged & years decreased by 38%, neither decreased in people aged ≥5 years. Fifteen years post-PCV and 5 years post-PCV13, direct and indirect impact on IPD and PnCAP differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings. Fifteen years after pneumococcal conjugate vaccine (PCV) introduction and 5 years post-PCV13, direct and indirect impact on invasive pneumococcal disease and pneumococcal community-acquired pneumonia differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.
Target-specific assay for rapid and quantitative detection of Mycobacterium chimaera DNA
Publisher: American Society for Microbiology
Date: 06-2017
DOI: 10.1128/JCM.00197-17
Abstract: Mycobacterium chimaera is an opportunistic environmental mycobacterium belonging to the Mycobacterium avium - M. intracellulare complex. Although most commonly associated with pulmonary disease, there has been growing awareness of invasive M. chimaera infections following cardiac surgery. Investigations suggest worldwide spread of a specific M. chimaera clone, associated with contaminated hospital heater-cooler units used during the surgery. Given the global dissemination of this clone, its potential to cause invasive disease, and the laboriousness of current culture-based diagnostic methods, there is a pressing need to develop rapid and accurate diagnostic assays specific for M. chimaera . Here, we assessed 354 mycobacterial genome sequences and confirmed that M. chimaera is a phylogenetically coherent group. In silico comparisons indicated six DNA regions present only in M. chimaera . We targeted one of these regions and developed a TaqMan quantitative PCR (qPCR) assay for M. chimaera with a detection limit of 100 CFU/ml in whole blood spiked with bacteria. In vitro screening against DNA extracted from 40 other mycobacterial species and 22 bacterial species from 21 erse genera confirmed the in silico -predicted specificity for M. chimaera . Screening 33 water s les from heater-cooler units with this assay highlighted the increased sensitivity of PCR compared to culture, with 15 of 23 culture-negative s les positive by M. chimaera qPCR. We have thus developed a robust molecular assay that can be readily and rapidly deployed to screen clinical and environmental specimens for M. chimaera .
Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand
Publisher: Oxford University Press (OUP)
Date: 22-11-2018
DOI: 10.1093/JAC/DKX405
Daptomycin selects for genetic and phenotypic adaptations leading to antibiotic tolerance in MRSA
Publisher: Oxford University Press (OUP)
Date: 27-04-2018
DOI: 10.1093/JAC/DKY148
Analysis of Hepatitis B Virus Haplotype Diversity Detects Striking Sequence Conservation Across Genotypes and Chronic Disease Phase
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-04-2021
DOI: 10.1002/HEP.31516
Abstract: We conducted haplotype analysis of complete hepatitis B virus (HBV) genomes following deep sequencing from 368 patients across multiple phases of chronic hepatitis B (CHB) infection from four major genotypes (A‐D), analyzing 4,110 haplotypes to identify viral variants associated with treatment outcome and disease progression. Between 18.2% and 41.8% of nucleotides and between 5.9% and 34.3% of amino acids were 100% conserved in all genotypes and phases examined, depending on the region analyzed. Hepatitis B e antigen (HBeAg) loss by week 192 was associated with different haplotype populations at baseline. Haplotype populations differed across the HBV genome and CHB history, this being most pronounced in the precore/core gene. Mean number of haplotypes (frequency) per patient was higher in immune‐active, HBeAg‐positive chronic hepatitis phase 2 (11.8) and HBeAg‐negative chronic hepatitis phase 4 (16.2) compared to subjects in the “immune‐tolerant,” HBeAg‐positive chronic infection phase 1 (4.3, P 0.0001). Haplotype frequency was lowest in genotype B (6.2, P 0.0001) compared to the other genotypes (A = 11.8, C = 11.8, D = 13.6). Haplotype genetic ersity increased over the course of CHB history, being lowest in phase 1, increasing in phase 2, and highest in phase 4 in all genotypes except genotype C. HBeAg loss by week 192 of tenofovir therapy was associated with different haplotype populations at baseline. Despite a degree of HBV haplotype ersity and heterogeneity across the phases of CHB natural history, highly conserved sequences in key genes and regulatory regions were identified in multiple HBV genotypes that should be further investigated as targets for antiviral therapies and predictors of treatment response.
Emergence of endemic MLST non-typeable vancomycin-resistant Enterococcus faecium
Publisher: Oxford University Press (OUP)
Date: 15-08-2016
DOI: 10.1093/JAC/DKW314
Abstract: Enterococcus faecium is a major nosocomial pathogen causing significant morbidity and mortality worldwide. Assessment of E. faecium using MLST to understand the spread of this organism is an important component of hospital infection control measures. Recent studies, however, suggest that MLST might be inadequate for E. faecium surveillance. To use WGS to characterize recently identified vancomycin-resistant E. faecium (VREfm) isolates non-typeable by MLST that appear to be causing a multi-jurisdictional outbreak in Australia. Illumina NextSeq and Pacific Biosciences SMRT sequencing platforms were used to determine the genome sequences of 66 non-typeable E. faecium (NTEfm) isolates. Phylogenetic and bioinformatics analyses were subsequently performed using a number of in silico tools. Sixty-six E. faecium isolates were identified by WGS from multiple health jurisdictions in Australia that could not be typed by MLST due to a missing pstS allele. SMRT sequencing and complete genome assembly revealed a large chromosomal rearrangement in representative strain DMG1500801, which likely facilitated the deletion of the pstS region. Phylogenomic analysis of this population suggests that deletion of pstS within E. faecium has arisen independently on at least three occasions. Importantly, the majority of these isolates displayed a vancomycin-resistant genotype. We have identified NTEfm isolates that appear to be causing a multi-jurisdictional outbreak in Australia. Identification of these isolates has important implications for MLST-based typing activities designed to monitor the spread of VREfm and provides further evidence supporting the use of WGS for hospital surveillance of E. faecium.
Rising incidence of invasive meningococcal disease caused by Neisseria meningitidis serogroup W in Victoria
Publisher: AMPCo
Date: 04-2016
DOI: 10.5694/MJA15.01222
Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: Resistance mechanisms, laboratory detection, and clinical implications
Publisher: American Society for Microbiology
Date: 2010
DOI: 10.1128/CMR.00042-09
Abstract: The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the ision septum however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus , it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus .
Treatment Outcomes for Rectal Lymphogranuloma Venereum in Men Who Have Sex with Men Using Doxycycline, Azithromycin, or Both: A Review of Clinical Cases
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2017
Comparative analysis of the complete genome of an epidemic hospital sequence type 203 clone of vancomycin-resistant Enterococcus faecium
Publisher: Springer Science and Business Media LLC
Date: 09-2013
Abstract: In this report we have explored the genomic and microbiological basis for a sustained increase in bloodstream infections at a major Australian hospital caused by Enterococcus faecium multi-locus sequence type (ST) 203, an outbreak strain that has largely replaced a predecessor ST17 sequence type. To establish a ST203 reference sequence we fully assembled and annotated the genome of Aus0085, a 2009 vancomycin-resistant Enterococcus faecium (VREfm) bloodstream isolate, and the first ex le of a completed ST203 genome. Aus0085 has a 3.2 Mb genome, comprising a 2.9 Mb circular chromosome and six circular plasmids (2 kb–130 kb). Twelve percent of the 3222 coding sequences (CDS) in Aus0085 are not present in ST17 E. faecium Aus0004 and ST18 E. faecium TX16. Extending this comparison to an additional 12 ST17 and 14 ST203 E. faecium hospital isolate genomes revealed only six genomic regions spanning 41 kb that were present in all ST203 and absent from all ST17 genomes. The 40 CDS have predicted functions that include ion transport, riboflavin metabolism and two phosphotransferase systems. Comparison of the vancomycin resistance-conferring Tn 1549 transposon between Aus0004 and Aus0085 revealed differences in transposon length and insertion site, and van locus sequence variation that correlated with a higher vancomycin MIC in Aus0085. Additional phenotype comparisons between ST17 and ST203 isolates showed that while there were no differences in biofilm-formation and killing of Galleria mellonella , ST203 isolates grew significantly faster and out-competed ST17 isolates in growth assays. Here we have fully assembled and annotated the first ST203 genome, and then characterized the genomic differences between ST17 and ST203 E. faecium . We also show that ST203 E. faecium are faster growing and can out-compete ST17 E. faecium . While a causal genetic basis for these phenotype differences is not provided here, this study revealed conserved genetic differences between the two clones, differences that can now be tested to explain the molecular basis for the success and emergence of ST203 E. faecium .
Preparation for fatherhood: A survey of men’s preconception health knowledge and behaviour in England
Publisher: Public Library of Science (PLoS)
Date: 20-03-2019
Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Australia
Publisher: Oxford University Press (OUP)
Date: 04-12-2014
DOI: 10.1093/JAC/DKU490
Inactivation of the Indigenous Methyltransferase RlmN in Staphylococcus aureus Increases Linezolid Resistance
Publisher: American Society for Microbiology
Date: 06-2011
DOI: 10.1128/AAC.00183-11
Abstract: The indigenous methyltransferase RlmN modifies A2503 in 23S rRNA. A recently described rlmN mutation in a clinical Staphylococcus aureus isolate decreases susceptibility to linezolid and was thought to increase the extent of A2503 modification. However, we show that the mutation in fact abolishes RlmN activity, resulting in a lack of A2503 modification. Since many mutations could inactivate the rlmN gene, our findings unveil a potential mechanism for future linezolid resistance in clinical strains.
Soil bacterial diffusible and volatile organic compounds inhibit Phytophthora capsici and promote plant growth
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.SCITOTENV.2019.07.061
Abstract: Biotic interactions through diffusible and volatile organic compounds (VOCs) are frequent in nature. Soil bacteria are well-known producers of a wide range of volatile compounds (both organic and inorganic) with various biologically relevant activities. Since the last decade, they have been identified as natural biocontrol agents. Volatiles are airborne chemicals, which when released by bacteria, can trigger plant responses such as defence and growth promotion. In this study, we tested whether diffusible and volatile organic compounds (VOCs) produced by soil bacterial isolates exert anti-oomycete and plant growth-promoting effects. We also investigated the effects of inoculation with VOC-producing bacteria on the growth and development of Capsicum annuum and Arabidopsis thaliana seedlings. Our results demonstrate that organic VOCs emitted by bacterial antagonists negatively influence mycelial growth of the soil-borne phytopathogenic oomycete Phytophthora capsici by 35% in vitro. The bacteria showed plant growth promoting effects by stimulating biomass production, primary root growth and root hair development. Additionally, we provide evidence to suggest that these activities were deployed by the emission of either diffusible organic compounds or VOCs. Bacterial VOC profiles were obtained through solid phase microextraction (SPME) and analysis by gas chromatography coupled with mass spectrometry (GC-MS). This elucidated the main volatiles emitted by the isolates, which covered a wide range of aldehydes, alcohols, esters, carboxylic acids, and ketones. Collectively, twenty-five VOCs were identified to be produced by three bacteria some being species-specific. Our data show that bacterial volatiles inhibits P. capsici in vitro and modulate both plant growth promotion and root system development. These results confirm the significance of soil bacteria and highlights that ways of harnessing them to improve plant growth, and as a biocontrol agent for soil-borne oomycetes through their volatile emissions deserve further investigation.
Remodelling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in Methicillin-ResistantStaphylococcus aureus
Publisher: Cold Spring Harbor Laboratory
Date: 31-10-2018
DOI: 10.1101/457838
Abstract: Staphylococcus aureus is a significant human pathogen whose evolution and adaptation has been shaped in part by mobile genetic elements (MGEs), facilitating global spread of extensive antimicrobial resistance. However, our understanding of the evolutionary dynamics surrounding MGEs is incomplete, in particular how changes in the structure of multidrug-resistant (MDR) plasmids may influence important staphylococcal phenotypes. Here, we undertook a population-and functional-genomics study of 212 methicillin-resistant S. aureus (MRSA) ST239 isolates collected over 32 years to explore the evolution of the pSK1 family of MDR plasmids, illustrating how these plasmids have co-evolved with and contributed to the successful adaptation of this persistent MRSA lineage. Using complete genomes and temporal phylogenomics we reconstructed the evolution of the pSK1 family lineage from its emergence in the late 1970s, with multiple structural variants arising. Plasmid maintenance and stability was linked to IS 256 - and IS 257 -mediated chromosomal integration and disruption of plasmid replication machinery. Overlaying genomic comparisons with phenotypic susceptibility data for gentamicin and chlorhexidine, it appeared that pSK1 has contributed to enhanced resistance in ST239 MRSA through two mechanisms: (i) acquisition of plasmid-borne resistance mechanisms increasing rates of gentamicin resistance and reduced chlorhexidine susceptibility, and (ii) changes in plasmid configuration linked with further enhancement of chlorhexidine tolerance. While the exact mechanism of enhanced tolerance remains elusive, this research has uncovered a clear evolutionary response of ST239 MRSA to chlorhexidine, one which may contribute to the ongoing persistence and adaptation of this lineage within healthcare institutions.
Genomic insights to control the emergence of vancomycin-resistant enterococci
Publisher: American Society for Microbiology
Date: 30-08-2013
Abstract: Nosocomial outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are thought to occur by transmission of VREfm between patients, predicting that infection control interventions will limit cross-transmission. Despite implementation of such strategies, the incidence of VREfm infections continues to rise. We aimed to use genomics to better understand the epidemiology of E. faecium within a large hospital and investigate the reasons for failure of infection control strategies. Whole-genome sequencing was performed on 61 E. faecium (36 VREfm) isolates, predominately from blood cultures collected at a single hospital between 1998 and 2009, and on five vanB -positive anaerobic commensal bacteria isolated from human feces. Phylogenomic analysis and precise mapping of the vanB gene, which contains the Tn 1549 transposon, showed that at least 18 of the 36 VREfm isolates had acquired the transposon via independent insertion events, indicating de novo generation of VREfm rather than cross-transmission. Furthermore, Tn 1549 sequences found in 15 of the 36 VREfm isolates were the same as the Tn 1549 sequence from one of the gut anaerobes. National and international comparator E. faecium isolates were phylogenetically interspersed with isolates from our hospital, suggesting that our findings might be globally representative. These data demonstrate that VREfm generation within a patient is common, presumably occurring in the human bowel during antibiotic therapy, and help explain our inability to reduce VREfm infections. A recommendation from our findings is that infection control practices should include screening patients for specific hospital clones of vancomycin-susceptible E. faecium rather than just VREfm. IMPORTANCE Enterococcus faecium is an increasingly important human pathogen causing predominantly antibiotic-resistant infections in hospitalized patients. Large amounts of health care funding are spent trying to control antibiotic-resistant bacteria in hospitals globally, yet in many institutions around the world, vancomycin-resistant E. faecium (VREfm) infections continue to rise. The new findings from this study help explain the failures of our current approaches to controlling vanB VREfm in health care institutions. Given the importance of this bacterium as a cause of hospital-acquired infections and the difficulties faced by infection control units in trying to prevent colonization in their institutions, the novel findings from this study provide evidence that a new approach to controlling VREfm in hospitals is required. In particular, more attention should be given to understanding the epidemiology of hospital-adapted vancomycin-susceptible E. faecium , and patients at higher risk for de novo generation of VREfm need to be identified and optimally managed.
A multi-institutional outbreak of New Delhi metallo-β-lactamase–producing Escherichia coli with subsequent acquisition of the Klebsiella pneumoniae carbapenemase gene
Publisher: Cambridge University Press (CUP)
Date: 29-12-2021
Abstract: We characterized 57 isolates from a 2-phase clonal outbreak of New Delhi metallo-β-lactamase–producing Eschericha coli , involving 9 Israeli hospitals all but 1 isolate belonged to sequence-type (ST) 410. Most isolates in the second phase harbored bla KPC-2 in addition to bla NDM-5 . Genetic sequencing revealed most dual-carbapenemase–producing isolates to be monophyletically derived from a common ancestor.
Antiseptic mouthwash for gonorrhoea prevention (OMEGA): a randomised, double-blind, parallel-group, multicentre trial
Publisher: Elsevier BV
Date: 05-2021
Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages
Publisher: Springer Science and Business Media LLC
Date: 14-10-2023
The two-component regulator WalKR provides an essential link between cell wall homeostasis with DNA replication inStaphylococcus aureus
Publisher: Cold Spring Harbor Laboratory
Date: 28-02-2023
DOI: 10.1101/2023.02.27.530350
Abstract: Among the 16 two-component systems (TCSs) in the opportunistic human pathogen Staphylococcus aureus , only WalKR is essential. Like orthologous systems in other Bacillota, S. aureus WalKR controls autolysins involved in peptidoglycan remodelling and is therefore intimately involved in cell ision. However, despite the importance of WalKR in S. aureus , the basis for its essentiality is not understood and the regulon poorly defined. Here, we defined a consensus WalR DNA-binding motif and the direct WalKR regulon by using functional genomics, including ChIP-seq, with a panel of isogenic walKR mutants that had a spectrum of altered activities. Consistent with prior findings, the direct regulon includes multiple autolysin genes. However, this work also revealed that WalR directly regulates at least five essential genes involved in lipoteichoic acid synthesis ( ltaS ) translation (rplK ) DNA compaction ( hup ) initiation of DNA replication ( dnaA, hup ) and purine nucleotide metabolism ( prs ). Thus, WalKR in S. aureus serves as a polyfunctional regulator that contributes to fundamental control over critical cell processes by co-ordinately linking cell wall homeostasis with purine biosynthesis, protein biosynthesis, and DNA replication. Collectively, our findings address the essentiality of this locus and highlight the importance of WalKR as a bona fide target for novel anti-staphylococcal therapeutics.
LED power efficiency of biomass, fatty acid, and carotenoid production in Nannochloropsis microalgae
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.BIORTECH.2017.12.096
Abstract: The microalga Nannochloropsis produces high-value omega-3-rich fatty acids and carotenoids. In this study the effects of light intensity and wavelength on biomass, fatty acid, and carotenoid production with respect to light output efficiency were investigated. Similar biomass and fatty acid yields were obtained at high light intensity (150 μmol m
Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Publisher: eLife Sciences Publications, Ltd
Date: 12-09-2023
DOI: 10.7554/ELIFE.85867
A high-throughput cytotoxicity screening platform reveals agr-independent mutations in bacteraemia-associated Staphylococcus aureus that promote intracellular persistence
Publisher: eLife Sciences Publications, Ltd
Date: 08-06-2023
DOI: 10.7554/ELIFE.84778
Abstract: Staphylococcus aureus infections are associated with high mortality rates. Often considered an extracellular pathogen, S. aureus can persist and replicate within host cells, evading immune responses, and causing host cell death. Classical methods for assessing S. aureus cytotoxicity are limited by testing culture supernatants and endpoint measurements that do not capture the phenotypic ersity of intracellular bacteria. Using a well-established epithelial cell line model , we have developed a platform called InToxSa ( in tracellular tox icity of S. a ureus ) to quantify intracellular cytotoxic S. aureus phenotypes. Studying a panel of 387 S . aureus bacteraemia isolates, and combined with comparative, statistical, and functional genomics, our platform identified mutations in S. aureus clinical isolates that reduced bacterial cytotoxicity and promoted intracellular persistence. In addition to numerous convergent mutations in the Agr quorum sensing system, our approach detected mutations in other loci that also impacted cytotoxicity and intracellular persistence. We discovered that clinical mutations in ausA , encoding the aureusimine non-ribosomal peptide synthetase, reduced S. aureus cytotoxicity, and increased intracellular persistence. InToxSa is a versatile, high-throughput cell-based phenomics platform and we showcase its utility by identifying clinically relevant S. aureus pathoadaptive mutations that promote intracellular residency.
A sustained hospital outbreak of vancomycin-resistant Enterococcus faecium bacteremia due to emergence of vanB E. faecium sequence type 203
Publisher: Oxford University Press (OUP)
Date: 15-10-2010
DOI: 10.1086/656319
Abstract: A significant increase in the rate of vancomycin-resistant Enterococcus faecium (VREfm) bacteremia at our health service, despite improved infection control, prompted us to investigate the cause. E. faecium bacteremia (including VREfm) over a 12-year period (1998-2009) was investigated using multilocus sequence typing, antibiotic and antiseptic susceptibility profiles, optical mapping, and whole genome sequencing of historical and recent isolates. For 10 years, the rate of bacteremia due to vanB VREfm remained stable and sequence type (ST) 17 was predominant. In 2005, ST203 vancomycin-susceptible E. faecium first appeared at our institution, and from March 2007, coinciding with the appearance of a vanB VREfm ST203, the rate of VRE bacteremia has increased exponentially. Although we found no difference in antiseptic susceptibility or presence of genes encoding putative virulence determinants (esp(Efm), hyl(Efm), and fms genes), comparative genomics revealed almost 500 kb of unique sequence when an ST17 and an ST203 VREfm isolate were compared, suggesting that other genomic factors are responsible for the apparent success of E. faecium. The application of multilocus sequence typing has uncovered the emergence of an epidemic clone of E. faecium ST203 that appears to have acquired the vanB locus and has caused a sustained outbreak of VRE bacteremia.
Participation in a Structured Weight Loss Program and All-Cause Mortality and Cardiovascular Morbidity in Obese Patients With Chronic Kidney Disease
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1053/J.JRN.2015.05.001
Abstract: To determine if participation in a weight loss program impacted upon a composite end point of all-cause mortality and cardiovascular morbidity in obese patients with chronic kidney disease (CKD). Retrospective cohort study. All patients with a body mass index (BMI) >30 kg/m(2) or >28 kg/m(2) with at least 1 comorbidity (hypertension, diabetes, or dyslipidemia) referred to an established weight management program (WMP) from 2005 to 2009 at a metropolitan tertiary teaching hospital were eligible for inclusion in the study cohort. Twelve-month structured weight loss program. Combined outcome of all-cause mortality, myocardial infarction, stroke, and hospitalization for congestive heart failure kidney transplantation waitlisting. A total of 169 obese patients with CKD commenced the WMP and 169 did not-becoming the observational control group (CON). There were no significant differences between groups for age, BMI, sex, ethnicity, smoking, hypertension, or kidney function at baseline, although CON included more patients with diabetes than WMP (49% vs. 38%, P = .03). Kaplan-Meier survival analysis with log-rank test differed between groups for the combined outcome (P = .03). Cox regression analysis with adjustment for age, sex, ethnicity, hypertension, diabetes, kidney function, baseline BMI, and smoking status, indicated that patients in WMP had a significantly longer event-free period for the combined outcome, than those in CON (adjusted hazard ratio 0.53 95% confidence interval [CI] 0.29-0.97 P = .04). Participation in the WMP did not increase the likelihood of kidney transplantation waitlisting (odds ratio [OR] 1.06 95% CI 0.39-2.87 P = .9). Lower baseline BMI and greater weight loss over 12 months were the only factors related to kidney transplantation waitlisting (adjusted R(2) = 0.426). Participation in a structured weight loss program may be associated with improved outcomes in obese patients with CKD.
A phylogenomic framework for assessing the global emergence and evolution of clonal complex 398 methicillin-resistant Staphylococcus aureus
Publisher: Microbiology Society
Date: 31-01-2017
Treatment ofStaphylococcus aureusinfections: new issues, emerging therapies and future directions
Publisher: Informa Healthcare
Date: 03-2007
Abstract: Infections due to Staphylococcus aureus are a major cause of morbidity and mortality worldwide. Antimicrobial resistance in strains of S. aureus is a continually evolving problem, including widespread methicillin resistance in hospitals, increasing methicillin resistance in community strains, and the recent acquisition of glycopeptide resistance. New antimicrobials with activity against S. aureus have recently entered the market or are in the late stages of development. In addition, there has been significant interest in the development of novel and immune-based strategies for prevention or treatment of S. aureus infections. This review describes established and emerging therapies for S. aureus infections, and considers the safety profiles and likely impact on present treatment standards of novel agents either undergoing clinical development or emerging onto the market.
Australia's response to the global threat of antimicrobial resistance: past, present and future
Publisher: Wiley
Date: 16-07-2019
DOI: 10.5694/MJA2.50264
Reply to Gould
Publisher: Oxford University Press (OUP)
Date: 11-01-2012
Antibiotics and Staphylococcus aureus - More than meets the MIC
Publisher: Springer Science and Business Media LLC
Date: 15-12-2014
Changes in leg strength 8 and 32 h after endurance exercise
Publisher: Informa UK Limited
Date: 2000
DOI: 10.1080/026404100750017797
Abstract: The aim of this study was to determine the effects of a single bout of endurance exercise on subsequent strength performance. Eight males with a long history of resistance training performed isokinetic, isometric and isotonic leg extension strength tests 8 and 32 h after 50 min of cycle ergometry at 70-110% of critical power. The participants also completed a control condition in which no cycling was performed. Plasma lactate and ammonia were measured before and immediately after each strength test. Isokinetic, isometric and isotonic leg extension torques were not significantly different 8 or 32 h after endurance exercise compared with the control condition (P > 0.05). A large (50.3%), but not statistically significant, increase in plasma ammonia was evident during the strength tests performed 8 h after endurance exercise, while a significant (P < 0.05) increase in ammonia was also seen 32 h after endurance exercise. No significant changes in plasma ammonia were evident in the control condition. Our results suggest that leg extension strength was not compromised by an earlier bout of endurance cycling. However, metabolic activity during the strength tests might have been altered by the preceding bout of endurance exercise.
Convergent Evolution Driven by Rifampin Exacerbates the Global Burden of Drug-Resistant Staphylococcus aureus.
Publisher: American Society for Microbiology
Date: 28-02-2018
Abstract: Increasing antibiotic resistance in the major human pathogen Staphylococcus aureus is threatening the ability to treat patients with these infections. Recent laboratory studies suggest that mutations in the gene commonly associated with rif in resistance may also impact susceptibility to other last-line antibiotics in S. aureus however, the overall frequency and clinical impact of these mutations are unknown. By mining a global collection of clinical S. aureus genomes and by mutagenesis experiments, this work reveals that common rif in-induced rpoB mutations promote phenotypic plasticity that has led to the global emergence of stable, multidrug-resistant S. aureus lineages that are associated with increased risk of therapeutic failure through coresistance to other last-line antimicrobials. We recommend decreasing susceptibility breakpoints for rif in to allow phenotypic detection of critical rpoB mutations conferring low resistance to rif in and reconsidering the appropriate use of rif in to reduce the fixation and spread of these deleterious mutations globally.
Detection of SARS-CoV-2 in saliva: implications for specimen transport and storage
Publisher: Microbiology Society
Date: 02-2021
DOI: 10.1099/JMM.0.001285
Abstract: Saliva has recently been proposed as a suitable specimen for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Use of saliva as a diagnostic specimen may present opportunities for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing in remote and low-resource settings. Determining the stability of SARS-CoV-2 RNA in saliva over time is an important step in determining optimal storage and transport times. We undertook an in vitro study to assess whether SARS-CoV-2 could be detected in contrived saliva s les. The contrived saliva s les comprised 10 ml pooled saliva spiked with gamma-irradiated SARS-CoV-2 to achieve a concentration of 2.58×10 4 copies ml SARS-CoV-2, which was subsequently ided into 2 ml aliquots comprising: (i) neat saliva and a 1 : 1 dilution with (ii) normal saline (iii) viral transport media, and (iv) liquid Amies medium. Contrived s les were made in quadruplicate, with two s les of each stored at either: (i) room temperature or (ii) 4 °C. SARS-CoV-2 was detected in all SARS-CoV-2 spiked s les at time point 0, day 1, 3 and 7 at both storage temperatures using the N gene RT-PCR assay and time point 0, day 1 and day 7 using the Xpert Xpress SARS-CoV-2 (Cepheid, Sunnyvale, USA) RT-PCR assay. The ability to detect SARS-CoV-2 in saliva over a 1 week period is an important finding that presents further opportunities for saliva testing as a diagnostic specimen for the diagnosis of SARS-CoV-2.
Research Priorities to Reduce Global Mortality From Newborn Infections by 2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2009
Emergence of multidrug resistance in locally-acquired human infections with Salmonella Typhimurium in Australia owing to a new clade harbouring blaCTX-M-9
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.IJANTIMICAG.2017.02.014
Abstract: Antimicrobial resistance in non-typhoidal Salmonella is a critical problem globally, with the emergence of resistance to third-generation cephalosporins (3GCs) a particular concern. The aim of this study was to use whole-genome sequencing (WGS) to characterise recently identified human and non-human isolates of 3GC-resistant Salmonella enterica subsp. enterica serovar Typhimurium from Australia. The Illumina NextSeq sequencing platform was used to determine the genome sequences of 78 S. Typhimurium definitive type 44 isolated in Australia between 1992 and 2016, including 31 3GC-resistant isolates. Phylogenetic and bioinformatics analyses were subsequently performed using a number of in silico tools. We report the emergence of 3GC resistance in locally-acquired Australian S. Typhimurium for the first time. Phenotypically resistant isolates of human and animal origin were geographically restricted and were found by WGS all to be closely related and to carry bla
Cell Membrane Adaptations Mediate β-Lactam-Induced Resensitization of Daptomycin-Resistant (DAP-R) Staphylococcus aureus In Vitro
Publisher: MDPI AG
Date: 11-05-2021
DOI: 10.3390/MICROORGANISMS9051028
Abstract: The reversal of daptomycin resistance in MRSA to a daptomycin-susceptible phenotype following prolonged passage in selected β-lactams occurs coincident with the accumulation of multiple point mutations in the mprF gene. MprF regulates surface charge by modulating the content and translocation of the positively charged cell membrane phospholipid, lysyl-phosphatidylglycerol (LPG). The precise cell membrane adaptations accompanying such β-lactam-induced mprF perturbations are unknown. This study examined key cell membrane metrics relevant to antimicrobial resistance among three daptomycin-resistant MRSA clinical strains, which became daptomycin-susceptible following prolonged exposure to cloxacillin (‘daptomycin-resensitized’). The causal role of such secondary mprF mutations in mediating daptomycin resensitization was confirmed through allelic exchange strategies. The daptomycin-resensitized strains derived either post-cloxacillin passage or via allelic exchange (vs. their respective daptomycin-resistant strains) showed the following cell membrane changes: (i) enhanced BODIPY-DAP binding (ii) significant reductions in LPG content, accompanied by significant increases in phosphatidylglycerol content (p 0.05) (iii) no significant changes in positive cell surface charge (iv) decreased cell membrane fluidity (p 0.05) (v) enhanced carotenoid content (p 0.05) and (vi) lower branched chain fatty acid profiles (antiso- vs. iso-), resulting in increases in saturated fatty acid composition (p 0.05). Overall, the cell membrane characteristics of the daptomycin-resensitized strains resembled those of parental daptomycin-susceptible strains. Daptomycin resensitization with selected β-lactams results in both definable genetic changes (i.e., mprF mutations) and a number of key cell membrane phenotype modifications, which likely facilitate daptomycin activity.
Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidime-avibactam - epidemiology, laboratory detection and treatment implications.
Publisher: Informa UK Limited
Date: 21-03-2018
DOI: 10.1080/14787210.2018.1453807
Abstract: Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the 're-discovery' of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam. Expert commentary: A key challenge for microbiologists and clinicians using these agents for treating patients with MDR and XDR Gram negative infections is the need to ensure appropriate reference methods are being used to test susceptibility to these agents, especially colistin and fosfomycin. These methods are not available in all laboratories meaning accurate results are either delayed, or potentially inaccurate as non-reference methods are employed. Combination therapy for MDR and XDR Gram negatives is likely to become more common, and future studies should focus on the clinical effects of monotherapy vs combination therapy, as well as validation of synergy testing methods. Effective national and international surveillance systems to detect and respond to resistance to these last line agents are also critical.
Risk Factors for Asymptomatic Enteric Pathogen Detection Among Men Who Have Sex With Men
Publisher: Oxford University Press (OUP)
Date: 11-07-2019
DOI: 10.1093/OFID/OFZ326
Abstract: Improved knowledge of factors that promote outbreaks of enteric pathogens among men who have sex with men (MSM) could enable targeted public health interventions. We detected enteric pathogens in 57 of 519 (11%) asymptomatic MSM, and we found that enteric pathogen detection was associated with both oroanal sex (rimming) and group sex.
Comprehensive antibiotic-linked mutation assessment by resistance mutation sequencing (RM-seq).
Publisher: Springer Science and Business Media LLC
Date: 31-08-2018
Relationship between Vancomycin-Resistant Staphylococcus aureus, Vancomycin-Intermediate S. aureus, High Vancomycin MIC, and Outcome in Serious S. aureus Infections
Publisher: American Society for Microbiology
Date: 08-2012
DOI: 10.1128/JCM.00775-12
Abstract: Vancomycin has been used successfully for over 50 years for the treatment of Staphylococcus aureus infections, particularly those involving methicillin-resistant S. aureus . It has proven remarkably reliable, but its efficacy is now being questioned with the emergence of strains of S. aureus that display heteroresistance, intermediate resistance, and, occasionally, complete vancomycin resistance. More recently, an association has been established between poor outcome and infections with strains of S. aureus with an elevated vancomycin MIC within the susceptible range. This minireview summarizes the definitions, mechanisms, clinical impact, and laboratory identification of reduced vancomycin susceptibility in S. aureus and discusses practical issues for the diagnostic laboratory in testing and interpreting vancomycin susceptibility for S. aureus infections.
Unstable chromosome rearrangements in Staphylococcus aureus cause phenotype switching associated with persistent infections.
Publisher: Proceedings of the National Academy of Sciences
Date: 16-09-2019
Abstract: Staphylococcus aureus small-colony variants (SCVs) are associated with unusually chronic and persistent infections despite active antibiotic treatment. The molecular basis for this clinically important phenomenon is poorly understood, h ered by the instability of the SCV phenotype. Here we investigated the genetic basis for an unstable S. aureus SCV that arose spontaneously while studying rif icin resistance. This SCV showed no nucleotide differences across its genome compared with a normal-colony variant (NCV) revertant, yet the SCV presented the hallmarks of S. aureus linked to persistent infection: down-regulation of virulence genes and reduced hemolysis and neutrophil chemotaxis, while exhibiting increased survival in blood and ability to invade host cells. Further genome analysis revealed chromosome structural variation uniquely associated with the SCV. These variations included an asymmetric inversion across half of the S. aureus chromosome via recombination between type I restriction modification system (T1RMS) genes, and the activation of a conserved prophage harboring the immune evasion cluster (IEC). Phenotypic reversion to the wild-type–like NCV state correlated with reversal of the chromosomal inversion (CI) and with prophage stabilization. Further analysis of 29 complete S. aureus genomes showed strong signatures of recombination between hsdMS genes, suggesting that analogous CI has repeatedly occurred during S. aureus evolution. Using qPCR and long-read licon deep sequencing, we detected subpopulations with T1RMS rearrangements causing CIs and prophage activation across major S. aureus lineages. Here, we have discovered a previously unrecognized and widespread mechanism of reversible genomic instability in S. aureus associated with SCV generation and persistent infections.
Obesity as a barrier to kidney transplantation: Time to eliminate the body weight bias?
Publisher: Wiley
Date: 02-04-2019
DOI: 10.1111/SDI.12783
Abstract: There is clear evidence that survival rates following transplantation far exceed those for remaining on dialysis, regardless of body size measured by body mass index (BMI). Studies over the past 15 years also suggest little to no difference in long-term outcomes, including graft survival and mortality, irrespective of BMI, in contrast to earlier evidence. However, weight bias still exists, as access to kidney transplantation remains inequitable in centers using arbitrary BMI limits. Clinicians faced with the decision regarding listing based on body size are not helped by conflicting recommendations in national and international guidelines. Therefore, in clinical practice, obesity, and recommendations for weight loss, remain a controversial issue when assessing suitability for kidney transplantation. Obesity management interventions in end-stage kidney disease (ESKD), whether for weight loss for transplantation listing or for slowing kidney disease progression, are under-explored in trial settings. Bariatric surgery is the most successful treatment for obesity, but carries increased risk in the ESKD population, and the desired outcome of kidney transplant listing is not guaranteed. Centers that limit transplants to those meeting arbitrary levels of body mass, rather than adopting an in idualized assessment approach, may be unfairly depriving many ESKD patients of the survival and quality of life benefits derived from kidney transplantation. However, robotic kidney transplantation surgery holds promise for reducing perioperative risks related to obesity, and may therefore represent an opportunity to remove listing criteria based on size.
Related Organisations
King's College Hospital
Location: United Kingdom of Great Britain and Northern Ireland
King's College London
Location: United Kingdom of Great Britain and Northern Ireland
Monash Medical Centre, Austin Health And The Alfred Hospital
Location: Australia
Related Funding Activities
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE170100093
Start Date: 2017
End Date: 07-2018
Amount: $510,000.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE120100025
Start Date: 03-2012
End Date: 03-2013
Amount: $380,000.00
Funder: Australian Research Council
View Funded ActivityLinkage Projects - Grant ID: LP150100849
Start Date: 09-2016
End Date: 12-2016
Amount: $191,400.00
Funder: Australian Research Council
View Funded Activity