ORCID Profile
0000-0001-8783-5323
Current Organisations
Institute of Clinical Pathology and Medical Research
,
Westmead Hospital
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Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.IJANTIMICAG.2014.12.014
Abstract: Ceftaroline is a novel cephalosporin with activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). The objective of this study was to investigate the susceptibility to ceftaroline of hospital-associated MRSA (HA-MRSA) isolates causing acute bacterial skin and skin-structure infections (ABSSSIs) in China and to examine their relationship by genotyping. A total of 251 HA-MRSA isolates causing ABSSSIs were collected from a multicentre study involving 56 hospitals in 38 large cities across 26 provinces in mainland China. All isolates were characterised by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, spa typing and detection of the Panton-Valentine leukocidin locus (lukS-PV and lukF-PV). Minimum inhibitory concentrations (MICs) of 14 antimicrobial agents, including ceftaroline, were determined by broth microdilution and were interpreted using Clinical and Laboratory Standards Institute breakpoints. The ceftaroline MIC50 and MIC90 values (MICs that inhibit 50% and 90% of the isolates, respectively) were 1 μg/mL and 2 μg/mL, respectively 33.5% (n=84) of the isolates studied were ceftaroline-non-susceptible, with MICs of 2 μg/mL, but no isolate exhibited ceftaroline resistance (MIC>2 μg/mL). All of the ceftaroline-non-susceptible isolates belonged to the predominant HA-MRSA clones: 95.2% (n=80) from MLST clonal complex 8 (CC8), with the remaining 4.8% (n=4) from CC5. The high rate of non-susceptibility to ceftaroline amongst HA-MRSA causing ABSSSIs in China is concerning.
Publisher: Elsevier BV
Date: 2015
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.
Publisher: Wiley
Date: 06-2004
DOI: 10.1111/J.1834-7819.2004.TB00057.X
Abstract: Histoplasmosis is a rare but serious fungal infection commonly presenting as mucosal ulceration of the oral cavity. It is increasingly recognized in Australia but the source of infection remains obscure and it is likely to be under-diagnosed. We report a case of chronic mucosal ulceration which failed to fully respond to periodontal therapy. Histology and culture of a gingival biopsy was consistent with histoplasmosis, and the patient responded favourably to treatment with oral itraconazole. Histoplasmosis may present to general dental practitioners as chronic mucosal ulceration and should be considered in the differential diagnosis of such lesions. Diagnosis is best made by culture and histology of biopsy specimens.
Publisher: Wiley
Date: 06-2015
DOI: 10.1111/IMJ.12772
Publisher: Elsevier BV
Date: 06-2015
Publisher: Research Square Platform LLC
Date: 23-05-2022
DOI: 10.21203/RS.3.RS-1683350/V1
Abstract: The emergence of resistance to antiviral drugs increasingly used to treat SARS-CoV-2 infections has been recognised as a significant threat to COVID-19 control. In addition, some SARS-CoV-2 variants of concern appear to be intrinsically resistant to several classes of these antiviral agents. Therefore, there is a critical need for rapid recognition of clinically relevant polymorphisms in SARS-CoV-2 genomes associated with significant reduction of drug activity in virus neutralisation experiments. Here we present SABRes, a bioinformatic tool, which leverages on expanding public datasets of SARS-CoV-2 genomes and allows detection of drug resistance mutations in consensus genomes as well as in viral subpopulations. We have applied SABRes to detect resistance-conferring mutations in over 25,000 genomes generated over the course of the SARS-CoV-2 pandemic in Australia.
Publisher: MyJove Corporation
Date: 06-08-2011
DOI: 10.3791/2781
Publisher: Oxford University Press (OUP)
Date: 19-01-2014
DOI: 10.1093/JAC/DKT526
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.
Publisher: Springer Science and Business Media LLC
Date: 09-07-2020
Publisher: Wiley
Date: 07-02-2015
DOI: 10.1111/JOCN.12779
Abstract: This paper explores patients' perspectives on infection prevention and control. Healthcare-associated infections are the most frequent adverse event experienced by patients. Reduction strategies have predominantly addressed front-line clinicians' practices patients' roles have been less explored. Video-reflexive ethnography. Fieldwork undertaken at a large metropolitan hospital in Australia involved 300 hours of ethnographic observations, including 11 hours of video footage. This paper focuses on eight occasions, where video footage was shown back to patients in one-on-one reflexive sessions. Viewing and discussing video footage of clinical care enabled patients to become articulate about infection risks, and to identify their own roles in reducing transmission. Barriers to detailed understandings of preventative practices and their roles included lack of conversation between patients and clinicians about infection prevention and control, and being ignored or contradicted when challenging perceived suboptimal practice. It became evident that to compensate for clinicians' lack of engagement around infection control, participants had developed a range of strategies, of variable effectiveness, to protect themselves and others. Finally, the reflexive process engendered closer scrutiny and a more critical attitude to infection control that increased patients' sense of agency. This study found that patients actively contribute to their own safety. Their success, however, depends on the quality of patient-provider relationships and conversations. Rather than treating patients as passive recipients of infection control practices, clinicians can support and engage with patients' contributions towards achieving safer care. This study suggests that if clinicians seek to reduce infection rates, they must start to consider patients as active contributors to infection control. Clinicians can engage patients in conversations about practices and pay attention to patient feedback about infection risk. This will broaden clinicians' understandings of infection control risks and behaviours, and assist them to support appropriate patient self-care behaviour.
Publisher: American Society for Microbiology
Date: 08-2010
DOI: 10.1128/JCM.02201-09
Abstract: The relatively high-level clonality of methicillin-resistant Staphylococcus aureus (MRSA) and its frequent high-level endemicity in nosocomial settings complicate the development of methods for rapid subtyping of MRSA strains that are capable of identifying person-to-person transmission in hospitals. Phage-derived open reading frame (PDORF) typing is an MRSA typing method targeting mobile genetic elements that was recently described and evaluated using a geographically restricted set of isolates. The objective of this study was to develop a multiplex PCR-reverse line blot (mPCR/RLB) assay for PDORF typing and to test its applicability on a broad range of isolates and in an environment where MRSA is highly endemic. The 16 targets were identified using a 23-primer-pair mPCR/RLB assay with two probes for each target. The method was evaluated using 42 MRSA reference strains, including those representing major international clones, and 35 isolates from episodes of suspected nosocomial transmission. In vivo stability was explored using 81 isolate pairs. Pulsed-field gel electrophoresis (PFGE) and spa typing were performed for comparison. Among the 42 reference strains, there were 33 PFGE subtypes, 30 PDORF types, and 22 spa types. Simpson's index of ersity was 0.987, 0.971, and 0.926 for PFGE subtyping, PDORF typing, and spa typing, respectively. Typing of clinical isolates by PDORF typing and PFGE demonstrated concordant results. mPCR/RLB-based PDORF typing has similar discriminatory power to that of PFGE, can assist in tracking MRSA transmission events in a setting of high-level endemicity, and has the advantage of being a high-throughput technique.
Publisher: Oxford University Press (OUP)
Date: 14-05-2015
DOI: 10.1093/JAC/DKV124
Publisher: American Society for Microbiology
Date: 2013
DOI: 10.1128/JCM.01406-12
Abstract: Knowledge concerning stability is important in the development and assessment of microbial molecular typing systems and is critical for the interpretation of their results. Typing system stability is usually measured as the fraction of isolates that change type after several in vivo passages, but this does not necessarily reflect in vivo stability. The aim of this study was to utilize survival analysis to provide an informative quantitative measure of in vivo stability and to compare the stabilities of various techniques employed in typing methicillin-resistant Staphylococcus aureus (MRSA). We identified 100 MRSA pairs (isolated from the same patient ≥1 month apart) and typed them using multilocus sequence typing (MLST), phage-derived open reading frame (PDORF) typing, toxin gene profiling (TGP), staphylococcal cassette chromosome mec (SCC mec ) subtyping, pulsed-field gel electrophoresis (PFGE), and spa sequence typing. Discordant isolate pairs, belonging to different MLST clonal complexes, were excluded, leaving 81 pairs for analysis. The stabilities of these methods were examined using Kaplan-Meier survival analysis, and discriminatory power was measured by Simpson's index of ersity. The probability percentages that the type remained unchanged at 6 months for spa sequence typing, TGP, multilocus variable number of tandem repeats analysis (MLVA), SCC mec subtyping, PDORF typing, and PFGE were 95, 95, 88, 82, 71, and 58, respectively, while the Simpson's indices of ersity were 0.48, 0.47, 0.70, 0.72, 0.89, and 0.88, respectively. Survival analysis using sequential clinical isolates adds an important quantitative dimension to the measurement of stability of a microbial typing system. Of the methods compared here, PDORF typing provides high discriminatory power, comparable with that of PFGE, and a level of stability suitable for MRSA surveillance and outbreak investigations.
Publisher: Springer Science and Business Media LLC
Date: 18-05-2022
DOI: 10.1038/S41467-022-30518-X
Abstract: Co-infections with different variants of SARS-CoV-2 are a key precursor to recombination events that are likely to drive SARS-CoV-2 evolution. Rapid identification of such co-infections is required to determine their frequency in the community, particularly in populations at-risk of severe COVID-19, which have already been identified as incubators for punctuated evolutionary events. However, limited data and tools are currently available to detect and characterise the SARS-CoV-2 co-infections associated with recognised variants of concern. Here we describe co-infection with the SARS-CoV-2 variants of concern Omicron and Delta in two epidemiologically unrelated adult patients with chronic kidney disease requiring maintenance haemodialysis. Both variants were co-circulating in the community at the time of detection. Genomic surveillance based on licon- and probe-based sequencing using short- and long-read technologies identified and quantified subpopulations of Delta and Omicron viruses in respiratory s les. These findings highlight the importance of integrated genomic surveillance in vulnerable populations and provide diagnostic pathways to recognise SARS-CoV-2 co-infection using genomic data.
Publisher: Oxford University Press (OUP)
Date: 10-08-2017
DOI: 10.1093/JAC/DKX268
Abstract: To examine antimicrobial susceptibility patterns and predictors of resistance among Shigella isolates in New South Wales (NSW), Australia during 2013-14 with emphasis on azithromycin. Cross-sectional analysis of all shigellosis cases (160) notified to public health authorities in NSW, Australia was performed. Among 160 Shigella isolates tested, 139 (86.9%) were susceptible to azithromycin, 104 (65.0%) to ciprofloxacin and 38 (23.7%) to co-trimoxazole. Ciprofloxacin resistance was 1.9 times more common in infections acquired in Australia compared with those acquired overseas, while azithromycin resistance was 8.5 times more common in males. We recommend ongoing reconsideration of guidelines for the treatment of shigellosis based on emerging resistance patterns. First-line therapy may need to be reconsidered based on local resistance rates due to common resistance to co-trimoxazole and ciprofloxacin. We recommend culture and susceptibility testing for suspected and proven shigellosis. Azithromycin susceptibility breakpoints for Shigella species may need to be species specific.
Publisher: American Society for Microbiology
Date: 10-2010
DOI: 10.1128/JCM.00351-10
Abstract: Staphylococcal cassette chromosome mec (SCC mec ) is a large mobile genetic element which is used frequently for subtyping of methicillin-resistant Staphylococcus aureus (MRSA) strains. MRSA SCC mec type IV not only predominates among community-acquired MRSA (CA-MRSA) strains but also is associated with several genetic lineages of hospital-acquired MRSA (HA-MRSA) and with other species. The objective of this study was to investigate the ersity of MRSA strains classified as SCC mec type IV by using a multiplex PCR-based reverse line blot (mPCR/RLB) hybridization assay as well as spa typing and pulsed-field gel electrophoresis (PFGE). Sixty-two primer pairs and 63 probes were designed to interrogate each open reading frame (ORF) of SCC mec type IV sequences. A set of 131 MRSA SCC mec type IV isolates were classified into 79 subtypes by this method. There was considerable concordance between SCC mec type IV subtyping, spa typing, and PFGE patterns for clinical isolates, and the stability of SCC mec type IV subtyping was comparable to that of the other two methods. Using an in-house computer program, we showed that a subset of 20 genetic markers could achieve the same level of discrimination between isolates as the full set of 62, with a Simpson's index of ersity of 0.975. SCC mec type IV has a much higher level of ersity than previously suggested. The application of the mPCR/RLB hybridization assay to MRSA SCC mec type IV subtyping can improve the discriminatory power and throughput of MRSA typing and has the potential to enhance rapid infection control surveillance and outbreak detection.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JCV.2016.11.005
Abstract: Ebola virus disease (EVD) is characterised by systemic viral replication, immuno-suppression, abnormal inflammatory responses, large volume fluid and electrolyte losses, and high mortality in under-resourced settings. There are various therapeutic strategies targeting EVD including vaccines utilizing different antigen delivery methods, antibody-based therapies and antiviral drugs. These therapies remain experimental, but received attention following their use particularly in cases treated outside West Africa during the 2014-15 outbreak, in which 20 (80%) out of 25 patients survived. Emerging data from current trials look promising and are undergoing further study, however optimised supportive care remains the key to reducing mortality from EVD.
Publisher: Elsevier BV
Date: 07-2013
Publisher: American Society for Microbiology
Date: 11-2013
DOI: 10.1128/JCM.01375-13
Abstract: The global spread of methicillin-resistant Staphylococcus aureus (MRSA) is a serious problem, particularly in mainland China. In order to better understand the national molecular epidemiology and resistance profiles of hospital-associated MRSA (HA-MRSA) in China, a laboratory-based multicenter surveillance study was conducted. Sixty-nine hospitals in 45 large cities in 27 provinces were involved, and a total of 1,141 HA-MRSA isolates were collected during the 6-month study period in 2011. All MRSA isolates were characterized by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCC mec ) typing, spa typing, detection of the Panton-Valentine leukocidin (PVL) locus ( lukS-PV and lukF-PV ), and antibiogram analysis. ST239-III-t030, ST239-III-t037, and ST5-II-t002 were the predominant HA-MRSA clones (overall prevalence rates, 57.1%, 12.9%, and 8.1%, respectively), although the prevalence rates of these major clones varied markedly in different administrative regions. Of note, 6.6% of the HA-MRSA isolates were found to belong to ST59, which had typical community-associated MRSA (CA-MRSA) features, including carriage of SCC mec type IV or V and PVL and less antimicrobial resistance than other major HA-MRSA clones. Moreover, among 36 MLST sequence types (STs) identified, 15 STs, accounting for 3.5% of total isolates, were novel. A novel ST designated ST2590, which is a single-locus variant of ST5-II-t002, was identified in three hospitals in two large cities, with a total of 17 isolates. To further monitor trends in HA-MRSA prevalence, epidemic clonal shifts, clone emergence, and transmission between community and health care settings, longitudinal national MRSA surveillance is required.
Publisher: Springer New York
Date: 03-10-2010
Publisher: American Society for Microbiology
Date: 12-2007
DOI: 10.1128/JCM.01158-07
Abstract: We describe the development and validation of an agar dilution method for the detection of inducible clindamycin resistance by using 227 previously characterized erythromycin-resistant, clindamycin-susceptible Staphylococcus sp. isolates. Mueller-Hinton agar with defibrinated horse blood containing a range of erythromycin concentrations (1 to 8 mg/liter) combined with clindamycin at 0.5 mg/liter was used to determine the optimal concentration that produced growth of inducible isolates while inhibiting that of isolates without the inducible phenotype. A concentration of clindamycin of 0.5 mg/liter with erythromycin at 1 mg/liter was the optimal combination for detection of inducible resistance and resulted in a sensitivity of 100% (95% confidence interval [CI], 97.9 to 100) and a specificity of 100% (95% CI, 93.0 to 100). Attention must be paid to ensuring that a sufficient inoculum has been used, since an inoculum below the standard 10 7 bacteria/ml may result in false-negative results. This method has been incorporated into routine use in our laboratory.
Publisher: Oxford University Press (OUP)
Date: 08-09-2016
DOI: 10.1093/CID/CIV808
Abstract: In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal β-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102% P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Combining an antistaphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger s le size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).
Publisher: Oxford University Press (OUP)
Date: 12-2005
DOI: 10.1086/497836
Abstract: Reduction of mortality associated with bacterial meningitis and postsurgical cerebral ventriculitis is dependent on early diagnosis and institution of appropriate therapy. Metabonomics rapidly defines metabolic profiles of biological fluids through the use of high-throughput analytical techniques combined with statistical pattern recognition tools. Proton nuclear magnetic resonance (1H NMR)-based metabonomics was applied to (1) lumbar cerebrospinal fluid s les collected prospectively from a cohort of patients with bacterial, fungal, or viral meningitis and from control subjects without neurological disease and (2) ventricular cerebrospinal fluid s les from patients with ventriculitis associated with an external ventricular drain and from control subjects. 1H NMR spectra were analyzed by the unsupervised statistical method of principal components analysis. Metabonomic analysis clearly distinguished patients with bacterial or fungal meningitis (11 patients) from patients with viral meningitis (12) and control subjects (27) and clearly distinguished patients with postsurgical ventriculitis (5) from postsurgical control subjects (10). Metabolites of microbial and host origin that were responsible for class separation were determined. Metabonomic data also correlated with the onset and course of infection in a patient with 2 episodes of bacterial ventriculitis and with response to therapy in another patient with cryptococcal meningitis. Metabonomic analysis is rapid, requires minimal s le processing, and is not targeted to specific microbial pathogens, making the platform potentially suitable for use in the diagnostic laboratory. This pilot study indicates that metabonomic analysis of cerebrospinal fluid is feasible and a potentially more powerful diagnostic tool than conventional rapid laboratory indicators for distinguishing bacterial from viral meningitis and for monitoring therapy. This should have important implications for early management, reduced empirical use of antibiotics, and treatment duration.
Publisher: Wiley
Date: 04-2015
DOI: 10.1111/IMJ.12719
Abstract: Delusional infestation remains a debilitating condition that is therapeutically challenging for clinicians. This case series identifies 23 patients with delusional infestation in an Australian setting. The majority of patients are women and unlikely to have a psychiatric comorbid background. The use of unnecessary anti-parasitic medication is prevalent.
Publisher: American Society for Microbiology
Date: 11-2006
DOI: 10.1128/JCM.01632-06
Abstract: We undertook this study to assess the accuracy of the clindamycin-erythromycin disk approximation test (D-test) for detection of inducible clindamycin resistance in Staphylococcus spp. One hundred sixty-three Staphylococcus aureus and 68 coagulase-negative Staphylococcus (CoNS) spp. which were erythromycin nonsusceptible but clindamycin susceptible were tested using the D-test performed at both 15-mm and 22-mm disk separations and compared with genotyping as the “gold standard.” The rate of inducible clindamycin resistance was 96.3% for S. aureus and 33.8% for CoNS spp. The sensitivities of the D-tests performed at 15 mm and 22 mm were 100% and 87.7%, respectively, and specificities were 100% for both. The use of 22-mm disk separation for the D-test to detect inducible clindamycin resistance results in an unacceptably high very major error rate (12.3%). All isolates with false-negative results harbored the ermA gene, and the majority were methicillin-resistant Staphylococcus aureus . False-negative results were associated with smaller clindamycin zone sizes and double-edged zones. We recommend using a disk separation distance of ≤15 mm. There is wide geographic variation in the rates of inducible clindamycin resistance, and each laboratory should determine the local rate before deciding whether to either perform the D-test routinely or else report that all erythromycin-resistant S. aureus isolates are also clindamycin resistant.
Publisher: Oxford University Press (OUP)
Date: 27-08-2020
DOI: 10.1093/OFID/OFAA387
Abstract: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibodies has become an important tool, complementing nucleic acid tests (NATs) for diagnosis and for determining the prevalence of coronavirus disease 2019 (COVID-19) in population serosurveys. The magnitude and persistence of antibody responses are critical for assessing the duration of immunity. A SARS-CoV-2-specific immunofluorescent antibody (IFA) assay for immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) was developed and prospectively evaluated by comparison to the reference standard of NAT on respiratory tract s les from in iduals with suspected COVID-19. Neutralizing antibody responses were measured in a subset of s les using a standard microneutralization assay. A total of 2753 in iduals were eligible for the study (126 NAT-positive prevalence, 4.6%). The median “window period” from illness onset to appearance of antibodies (range) was 10.2 (5.8–14.4) days. The sensitivity and specificity of either SARS-CoV-2 IgG, IgA, or IgM when collected ≥14 days after symptom onset were 91.3% (95% CI, 84.9%–95.6%) and 98.9% (95% CI, 98.4%–99.3%), respectively. The negative predictive value was 99.6% (95% CI, 99.3%–99.8%). The positive predictive value of detecting any antibody class was 79.9% (95% CI, 73.3%–85.1%) this increased to 96.8% (95% CI, 90.7%–99.0%) for the combination of IgG and IgA. Measurement of SARS-CoV-2-specific antibody by IFA is an accurate method to diagnose COVID-19. Serological testing should be incorporated into diagnostic algorithms for SARS-CoV-2 infection to identify additional cases where NAT was not performed and resolve cases where false-negative and false-positive NATs are suspected. The majority of in iduals develop robust antibody responses following infection, but the duration of these responses and implications for immunity remain to be established.
Publisher: Springer Science and Business Media LLC
Date: 05-2013
Publisher: American Society for Microbiology
Date: 12-2008
DOI: 10.1128/JCM.01146-08
Publisher: Oxford University Press (OUP)
Date: 2008
DOI: 10.1080/13693780701874515
Abstract: While most patients with cryptococcosis have obvious cellular immune deficiency, a minority have no apparent predisposing factors. However, in the latter there may be subtle innate immune system deficiencies which go unrecognized. Mannose-binding lectin (MBL) deficiency is associated with increased susceptibility to infectious diseases and may predispose to cryptococcosis, particularly when it disseminates to the central nervous system (CNS) in apparently immunocompetent patients. MBL function and levels, as well as MBL2 genotype were determined in 36 HIV-negative cryptococcosis patients (25 with CNS involvement) using C4 deposition and mannan-binding ELISA. MBL deficiency was defined using C4 deposition level < 0.2 U/microl or mannan-binding level < 0.5 microg/ml. MBL results were compared between patients with cryptococcosis and healthy controls and among the cryptococcosis patients according to the site of their disease. There was no difference in MBL function, mannan-binding level or increase in the frequency of MBL deficiency or low producing MBL2 genotypes in any of these comparisons. Patients with CNS cryptococcosis were no more likely to be MBL deficient than those with non-CNS disease. It appears that MBL deficiency is not associated with cryptococcosis in non-immunocompromised hosts. Beta errors consequent on the small number of patients studied may account for the lack of association.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.MEEGID.2014.11.004
Abstract: Chlamydia trachomatis is a common sexually-transmitted bacterial pathogen. As no routine screening is performed during pregnancy, neonates and infants are at high risk for C. trachomatis infection. The objective of this study was to investigate the morbidity, clinical characteristics and genotype distribution of C. trachomatis pneumonia in infants less than six months of age. Clinical manifestations and laboratory results were recorded. Respiratory sputum specimens were tested using RT-PCR targeting C. trachomatis cryptic plasmid. Simultaneously, respiratory virus antigens were detected by direct immunofluorescence and bacterial pathogens were examined by culture in all sputum s les. Positive C. trachomatis s les were further genotyped using a multiplex PCR reverse line blot assay. The relationship between genotype and pneumonia severity was explored. Of 1408 infants, 101 (7.2%) were infected with C. trachomatis. Sixteen of 101 (15.8%) were assessed as severe pneumonia. These severe cases had a higher proportion of viral co-infection (37.5%) compared to mild pneumonia cases (9.4%, P<0.05).Infants with tachypnea (OR 9.2) and wheezing (OR 3.5) were more likely to be classified as severe pneumonia (P<0.05). Amongst 66 C. trachomatis specimens for which a genotyping result was available, seven genotypes were detected, and 39.4% of these specimens contained two or three genotypes. Overall, genotype E (48.5%) was the most frequent, followed by genotype F (42.4%), J (31.8%), D (12.1%), K (10.6%), G (4.5%) and H (3.0%). There were no significant correlations of particular genotypes with severity of disease, although there was a weak indication that more severe pneumonia might be associated with having certain mixed genotypes of C. trachomatis. The prevalence of C. trachomatis in the population of young hospitalized infants with pneumonia in Shenzhen was very high. The relationship between genotype distribution and severity of pneumonia was not clear based on this study due to small s le size. Further in-depth investigation correlating genotype and disease severity based on a larger population is needed.
Publisher: Springer Science and Business Media LLC
Date: 31-03-2016
Publisher: Public Library of Science (PLoS)
Date: 11-02-2016
Publisher: Wiley
Date: 06-2013
DOI: 10.1111/IMJ.12160
Publisher: Microbiology Society
Date: 10-2014
Abstract: Human enteroviruses evolve quickly. The 5′ untranslated region (UTR) is fundamentally important for efficient viral replication and for virulence the VP1 region correlates well with antigenic typing by neutralization, and can be used for virus identification and evolutionary studies. In order to investigate the molecular ersity in EV-B species, the 5′ UTR and VP1 regions were analysed for 208 clinical isolates from a single public-health laboratory (serving New South Wales, Australia), representing 28 EV-B types. Sequences were compared with the 5′ UTR and VP1 regions of 98 strains available in GenBank, representing the same 28 types. The genetic relationships were analysed using two types of software ( mega and BioNumerics). The sequence analyses of the 5′ UTR and VP1 regions of 306 EV-B strains demonstrated that: (i) comparing the two regions gives strong evidence of epidemiological linkage of strains in some serotypes (ii) the intraserotypic genetic variation within each gene reveals that they evolve distinctly largely due to their different functions and (iii) mutation and possible recombination in the two regions play significant roles in the molecular ersity of EV-B. Understanding the tempo and pattern of molecular ersity and evolution is of great importance in the pathogenesis of EV-B enteroviruses, information which will assist in disease prevention and control.
Publisher: Public Library of Science (PLoS)
Date: 10-03-2016
Publisher: BMJ
Date: 30-11-2016
DOI: 10.1136/BMJQS-2016-005878
Abstract: Hospital-acquired infections are the most common adverse event for inpatients worldwide. Efforts to prevent microbial cross-contamination currently focus on hand hygiene and use of personal protective equipment (PPE), with variable success. Better understanding is needed of infection prevention and control (IPC) in routine clinical practice. We report on an interventionist video-reflexive ethnography study that explored how healthcare workers performed IPC in three wards in two hospitals in New South Wales, Australia: an intensive care unit and two general surgical wards. We conducted 46 semistructured interviews, 24 weeks of fieldwork (observation and videoing) and 22 reflexive sessions with a total of 177 participants (medical, nursing, allied health, clerical and cleaning staff, and medical and nursing students). We performed a postintervention analysis, using a modified grounded theory approach, to account for the range of IPC practices identified by participants. We found that healthcare workers' routine IPC work goes beyond hand hygiene and PPE. It also involves, for instance, the distribution of team members during rounds, the choreography of performing aseptic procedures and moving 'from clean to dirty' when examining patients. We account for these practices as the logistical work of moving bodies and objects across boundaries, especially from contaminated to clean/vulnerable spaces, while restricting the movement of micro-organisms through cleaning, applying barriers and buffers, and trajectory planning. Attention to the logistics of moving people and objects around healthcare spaces, especially into vulnerable areas, allows for a more comprehensive approach to IPC through better contextualisation of hand hygiene and PPE protocols, better identification of transmission risks, and the design and promotion of a wider range of preventive strategies and solutions.
Publisher: American Society for Microbiology
Date: 12-2015
DOI: 10.1128/JCM.02155-15
Abstract: The BD Max StaphSR assay is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). A total of 460 specimens were tested, and the results were compared with standard culture-based identification. MRSA was detected in 48 s les (sensitivity of 100% positive predictive value [PPV] of 100%). MSSA was detected in 112 s les (sensitivity of 99.1% PPV of 100%), and 299 s les containing coagulase-negative staphylococcus and nonstaphylococcal species were negative by the BD Max StaphSR assay (specificity of 100% negative predictive value [NPV] of 99.7 to 100%).
Publisher: Elsevier BV
Date: 06-2017
Publisher: Wiley
Date: 22-02-2017
DOI: 10.1111/HIV.12504
Publisher: American Society for Microbiology
Date: 11-2012
DOI: 10.1128/JCM.01625-12
Abstract: In settings of high methicillin-resistant Staphylococcus aureus (MRSA) prevalence, detection of nosocomial transmission events can be difficult without strain typing. Prospective typing of all MRSA isolates could potentially identify transmission in a timely fashion, making infection control responses to outbreaks more effective. We describe the development and evaluation of a novel 19-target binary typing system for MRSA using the multiplex-PCR/reverse line blot hybridization platform. Pulse-field gel electrophoresis (PFGE), spa typing, and phage-derived open reading frame (PDORF) typing were performed for comparison. The system was utilized to identify transmission events in three general surgical wards over a 12-month period. Initial MRSA isolates from 273 patients were differentiated into 55 unique binary types. One or more potential contacts colonized with the same MRSA strain were identified in 69 of 87 cases (79%) in which definite or possible nosocomial MRSA acquisition had occurred. The discriminatory power of the typing system was similar to that of PFGE (Simpson's index of ersity [ D ] = 0.994, versus 0.987) and higher than that of spa typing ( D = 0.926). Strain typing reduced the total number of potential MRSA-colonized source contacts from 859 to 212 and revealed temporal clustering of transmission events. Prospective MRSA typing using this novel binary typing method can rapidly identify nosocomial transmission events, even in high-prevalence settings, which allows timely infection control interventions. The system is rapid, inexpensive, discriminatory, and suitable for routine, high-throughput use in the hospital microbiology laboratory.
Publisher: Elsevier BV
Date: 12-2013
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.JHIN.2011.04.023
Abstract: Staphylococcus aureus bacteraemia (SAB) is associated with significant morbidity and mortality, yet there are limited data on preventable factors. This study aimed to evaluate SAB episodes at a tertiary care hospital to identify factors that, if avoided, might have prevented the episode of SAB and to provide feedback to treating clinicians. Of 187 episodes of SAB over 19 months 59.9% were caused by meticillin-susceptible S. aureus (MSSA) and 40.1% meticillin-resistant S. aureus (MRSA), 65.8% of SAB were healthcare-associated (HA) and 34.2% were community-acquired. Seven- and 30-day mortality rates, overall, were 11.2% and 20.9% respectively. At least one preventable factor was identified in 50.4% of HA-SAB episodes, including recent nosocomial MRSA acquisition in 53.7% MRSAB episodes and one or more factors associated with intravenous access in at least 24.3% of HA (35.7% of hospital onset) cases. SAB was more likely to be associated with at least one identifiable, preventable factor in surgical than in medical inpatients (86.2% vs 54.5%, P=0.004). Patients with HA-MRSAB were more likely than those with HA-MSSAB to require intensive care unit admission (44.4% vs 18.8%, P=0.003). Identifying and addressing preventable factors will better target resources for prevention of SAB. Feedback about preventable factors was associated with a reduction in HA-SAB rates from 0.29 to 0.20 per 1000 occupied bed-days, from 2008 to 2009.
Publisher: Elsevier BV
Date: 06-2021
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.
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.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
No related grants have been discovered for Matthew O'Sullivan.