ORCID Profile
0000-0001-7850-6931
Current Organisations
Fiona Stanley Hospital
,
Pathwest Laboratory Medicine
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Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12595
Abstract: There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.CMI.2014.12.021
Abstract: The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%) antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01) 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19-275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4% HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected erse patient groups, including non-immunocompromised hosts and those outside traditional risk groups therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12596
Abstract: Invasive fungal disease (IFD) causes significant morbidity and mortality in patients undergoing allogeneic haemopoietic stem cell transplantation or chemotherapy for haematological malignancy. Much of these adverse outcomes are due to the limited ability of traditional diagnostic tests (i.e. culture and histology) to make an early and accurate diagnosis. As persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients despite broad-spectrum antibiotics have been associated with the development of IFD, most centres have traditionally administered empiric antifungal therapy (EAFT) to patients with PFUO. However, use of an EAFT strategy has not been shown to have an overall survival benefit and is associated with excessive antifungal therapy use. As a result, the focus has shifted to developing more sensitive and specific diagnostic tests for early and more targeted antifungal treatment. These tests, including the galactomannan enzyme-linked immunosorbent assay and Aspergillus polymerase chain reaction (PCR), have enabled the development of diagnostic-driven antifungal treatment (DDAT) strategies, which have been shown to be safe and feasible, reducing antifungal usage. In addition, the development of effective antifungal prophylactic strategies has changed the landscape in terms of the incidence and types of IFD that clinicians have encountered. In this review, we examine the current role of EAFT and provide up-to-date data on the newer diagnostic tests and algorithms available for use in EAFT and DDAT strategies, within the context of patient risk and type of antifungal prophylaxis used.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 02-2008
Publisher: Wiley
Date: 10-2019
DOI: 10.1111/IMJ.14612
Abstract: Candida auris is an emerging drug-resistant yeast responsible for hospital outbreaks. This statement reviews the evidence regarding diagnosis, treatment and prevention of this organism and provides consensus recommendations for clinicians and microbiologists in Australia and New Zealand. C. auris has been isolated in over 30 countries (including Australia). Bloodstream infections are the most frequently reported infections. Infections have crude mortality of 30-60%. Acquisition is generally healthcare-associated and risks include underlying chronic disease, immunocompromise and presence of indwelling medical devices. C. auris may be misidentified by conventional phenotypic methods. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry or sequencing of the internal transcribed spacer regions and/or the D1/D2 regions of the 28S ribosomal DNA are therefore required for definitive laboratory identification. Antifungal drug resistance, particularly to fluconazole, is common, with variable resistance to hotericin B and echinocandins. Echinocandins are currently recommended as first-line therapy for infection in adults and children ≥2 months of age. For neonates and infants <2 months of age, hotericin B deoxycholate is recommended. Healthcare facilities with C. auris should implement a multimodal control response. Colonised or infected patients should be isolated in single rooms with Standard and Contact Precautions. Close contacts, patients transferred from facilities with endemic C. auris or admitted following stay in overseas healthcare institutions should be pre-emptively isolated and screened for colonisation. Composite swabs of the axilla and groin should be collected. Routine screening of healthcare workers and the environment is not recommended. Detergents and sporicidal disinfectants should be used for environmental decontamination.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-11-2005
Publisher: Wiley
Date: 06-2008
DOI: 10.1111/J.1445-5994.2008.01723.X
Abstract: Antifungal prophylaxis can be recommended in patients undergoing induction chemotherapy for acute myeloid leukemia and treatment for grade 2 or greater or chronic extensive graft versus host disease. The evidence for prophylaxis is less clear in other clinical settings although certain groups such as patients with prolonged neutropenia after stem cell transplants using bone marrow or cord blood sources and with impaired cell mediated immunity secondary to treatments such as Alemtuzumab are at high risk. The decision to use prophylaxis and which agent to use will be influenced by effectiveness, number needed to treat and the likelihood of toxicity and drug interactions. The availability of rapid diagnostic tests for fungal infection and institutional epidemiology will also influence the need for and choice of prophylaxis. Whilst prophylaxis can be beneficial, it may impede the ability to make a rapid diagnosis of fungal infection by reducing the yield of diagnostic tests and change the epidemiology of fungal infection. As non-culture based diagnostic tests are refined and become more available there may be a shift from prophylaxis to early diagnosis and treatment.
Publisher: Oxford University Press (OUP)
Date: 11-1997
DOI: 10.1086/516963
Abstract: Adoptive T cell therapies (ACT) have been curative for a limited number of cancer patients. The sensitization of cancer cells to T cell killing may expand the benefit of these therapies for more patients. To this end, we use a three-step approach to identify cancer genes that disfavor T cell immunity. First, we profile gene transcripts upregulated by cancer under selection pressure from T cell killing. Second, we identify potential tumor gene targets and pathways that disfavor T cell killing using signaling pathway activation libraries and genome-wide loss-of-function CRISPR-Cas9 screens. Finally, we implement pharmacological perturbation screens to validate these targets and identify BIRC2, ITGAV, DNPEP, BCL2, and ERRα as potential ACT-drug combination candidates. Here, we establish that BIRC2 limits antigen presentation and T cell recognition of tumor cells by suppressing IRF1 activity and provide evidence that BIRC2 inhibition in combination with ACT is an effective strategy to increase efficacy.
Publisher: Springer Science and Business Media LLC
Date: 14-10-2021
DOI: 10.1186/S13045-021-01177-0
Abstract: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. The study s le includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients ( n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.
Publisher: Elsevier BV
Date: 2023
Publisher: Oxford University Press (OUP)
Date: 29-05-2012
DOI: 10.1093/JAC/DKS210
Abstract: Scedosporium species are increasingly recognized as a cause of invasive mould disease in haematology patients, but little is known about the hospitalization costs and outcomes attributable to invasive scedosporiosis (SCEDO). A retrospective case-control study was undertaken during 2002-10 to determine the attributable inpatient costs, length of stay (LOS) and mortality associated with SCEDO in haematology patients. Case patients with SCEDO (n = 30) were matched 1 : 2 to controls (n = 60) according to haematological diagnosis, admission year and age. Diagnostics, antifungal drugs, ward and other SCEDO-related costs were estimated using actual cost data. Median regression modelling was used to adjust for variables that were not accounted for in the matched-pairs analysis. The crude total median cost of treating SCEDO was AU$32 182 per patient versus AU$17 424 per control. In multivariable analysis, SCEDO was associated with median excess costs of AU$23 611 (95% CI = AU$17 992-AU$29 231 P < 0.001), approximating US$15 509 at purchasing power parity, with prolonged LOS of 13 days (95% CI = 8.2-17.8 days P < 0.001). Exclusion of cases and matched pairs with early death further increased the median excess cost and LOS. The cost differential was driven by ward costs (64%, P = 0.005) and antifungal treatment costs (29%, P < 0.001). The all-cause inpatient mortality was 38 times higher for the SCEDO cases versus the control group (63.3% versus 1.7% P < 0.001). SCEDO has substantial impact on hospital resource consumption, LOS and mortality in haematology patients. Risk factors and preventative measures for SCEDO should be further studied.
Publisher: American Society for Microbiology
Date: 28-04-2020
Abstract: In less than a decade, C. auris has emerged in health care settings worldwide this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.
Publisher: Oxford University Press (OUP)
Date: 16-04-2012
Publisher: Oxford University Press (OUP)
Date: 15-05-2008
DOI: 10.1086/586749
Abstract: Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15% influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2002
DOI: 10.1097/01.ASN.0000022890.29656.22
Abstract: Tunneled catheters are widely used for the provision of hemodialysis. Long-term catheter survival is limited by tunneled catheter-related infections (CRI). This study assesses the efficacy of catheter-restricted filling with gentamicin and citrate in preventing CRI in hemodialysis patients. A double-blind randomized study was conducted to compare heparin (5000 U/ml) with gentamicin/citrate (40 mg/ml and 3.13% citrate ratio 2:1) as catheter-lock solutions. A total of 112 tunneled catheters in 83 patients were enrolled at the time of catheter insertion for commencement or maintenance of hemodialysis. The primary end point was CRI. Catheter malfunction, defined as blood flow rate of <200 ml/min for three consecutive dialyses and/or the use of urokinase, was also assessed as a secondary end point. Infection rates per 100 catheter-days were 0.03 in the gentamicin group versus 0.42 in the heparin group (P = 0.003). Kaplan-Meier survival analyses showed mean infection-free catheter survival of 282 d (95% CI, 272 to 293 d) in the gentamicin group versus 181 d (95% CI, 124 to 237 d) in the heparin group (log rank, 9.58 P = 0.002). Cox regression analyses showed a relative risk for infection-free catheter survival of 0.10 (95% CI, 0.01 to 0.92) in the gentamicin group when adjusted for gender, race, diabetes mellitus, catheter malfunction, and hemoglobin (P = 0.042). The incidence of catheter malfunction was not significantly different between groups. Predialysis gentamicin levels were significantly higher in patients randomized to gentamicin (gentamicin/citrate: median 2.8 mg/L [range, 0.6 to 3.5 mg/L], n = 5 heparin: median <0.2 mg/L [range <0.2 to 0.2 mg/L], n = 5 P = 0.008). Tunneled hemodialysis catheter-restricted filling with gentamicin and citrate is a highly effective strategy for prevention of CRI. Although citrate as a catheter-lock solution provides adequate anticoagulation for the interdialytic period, gentamicin levels suggest significant risk for chronic aminoglycoside exposure and associated ototoxicity. Before this technique is adopted, these preliminary observations warrant replication in future studies that will examine the efficacy and safety of lower doses of gentamicin or alternative agents with a reduced potential for toxicity.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.BURNS.2009.03.002
Abstract: First-aid education for the management of burns advocates cool running water over burnt skin to limit soft tissue damage. However, the water used may itself constitute a risk. We report three cases of severe invasive and necrotizing infection in patients who used or immersed themselves in contaminated water in an attempt to extinguish the fire following acute major burns. Wound cultures from all patients yielded Aeromonas hydrophila and two yielded Bacillus cereus. One patient had a complex polymicrobial infection, including zygomycosis with Rhizomucor variabilis. All patients were treated aggressively with wound débridement, including one patient who required bilateral lower limb utations to control progressive infection. All infections were successfully treated and all patients survived their burn injuries. We review the management of burns complicated by exposure to contaminated water leading to burn wound infections. We describe commonly reported organisms from various water sources, the appropriate initial empirical antimicrobial chemotherapy and present the clinician with a proposed algorithm for managing these serious infections.
Publisher: OMICS Publishing Group
Date: 2016
Publisher: American Society for Microbiology
Date: 18-01-2022
DOI: 10.1128/AAC.01624-21
Abstract: ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities.
Publisher: MDPI AG
Date: 13-03-2020
DOI: 10.3390/JOF6010036
Abstract: Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases (n = 69 49%), hematology (n = 68 48%), and others (n = 41 29%). BCT was performed in 57% (n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9% IQR 5–15%) and non-BCT centers (7% IQR 5–10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% (n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome.
Publisher: The Royal Australian College of General Practitioners
Date: 05-2019
Publisher: Cold Spring Harbor Laboratory
Date: 17-08-2021
DOI: 10.1101/2021.08.16.456589
Abstract: ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar, yet diminished pattern of reduced susceptibility was observed with long-tailed triazoles posaconazole and itraconazole for V125A/F126L, F126L, Y132F, and K143R alleles.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 03-2023
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 10-2006
Abstract: Population-based surveillance for candidemia in Australia from 2001 to 2004 identified 1,095 cases. Annual overall and hospital-specific incidences were 1.81/100,000 and 0.21/1,000 separations (completed admissions), respectively. Predisposing factors included malignancy (32.1%), indwelling vascular catheters (72.6%), use of antimicrobial agents (77%), and surgery (37.1%). Of 919 episodes, 81.5% were inpatient healthcare associated (IHCA), 11.6% were outpatient healthcare associated (OHCA), and 6.9% were community acquired (CA). Concomitant illnesses and risk factors were similar in IHCA and OHCA candidemia. IHCA candidemia was associated with sepsis at diagnosis (p<0.001), death <30 days after infection (p<0.001), and prolonged hospital admission (p or =65 years of age. Adult critical care stay, sepsis syndrome, and corticosteroid therapy were associated with the greatest risk for death. Systematic epidemiologic studies that use standardized definitions for IHCA, OHCA, and CA candidemia are indicated.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.JINF.2010.08.004
Abstract: Central nervous system (CNS) cryptococcosis is most commonly encountered among HIV-infected and other immunosuppressed hosts but is less well-characterized among non-immunosuppressed patients. We conducted a three year, prospective, observational study to compare the clinical manifestations and outcome of CNS cryptococcosis in three patient populations: HIV-infected patients (n = 54), HIV-negative immunosuppressed patients (n = 21), and non-immunosuppressed patients (n = 11). Time from initial symptoms to presentation did not differ between the groups. HIV-infected patients were significantly more likely to present with fevers (p < 0.0001), but were less likely to have abnormal mental status, CNS mass lesions and pulmonary involvement (p = 0.001, 0.01 and 0.03, respectively). The clinical manifestations among HIV-negative immunosuppressed patients were generally intermediate to the other groups. Overall, acuity of illness was worse among non-immunosuppressed patients, as measured by APACHE II scores (p = 0.02). Intracranial pressure was higher in HIV-infected and non-immunosuppressed patients than immunosuppressed patients (p = 0.008 and 0.01, respectively). Repeated lumbar punctures were more common among HIV-infected patients (p = 0.01). There was a trend toward more frequent placement of permanent CNS shunts among non-HIV patients (p = 0.05). The mortality rate was greatest for non-immunosuppressed patients (p = 0.04). CNS cryptococcosis in non-immunosuppressed patients was associated with poorer prognosis. Our findings suggest that host immune responses may contribute to pathogenesis of CNS cryptococcosis, with more intact immune function associated with increased CNS-related morbidity and overall mortality.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 2019
Publisher: Oxford University Press (OUP)
Date: 04-2023
DOI: 10.1093/MMY/MYAD028
Abstract: Time-to-positivity (TTP) may assist in predicting the outcome of candidaemia. We analysed a candidaemia dataset collected prospectively in Australia over 1 year (2014–2015). TTP was defined as the period from blood culture s ling to the blood culture flagging positive. Of 415 candidaemia episodes, overall, 30-day mortality was 29% (120/415) mortality with Candida albicans was 35% (59/169), C. glabrata complex, 37% (43/115), C. tropicalis, 43% (10/23), Pichia kudriavzevii 25% (3/12), and C. parapsilosis complex 7% (5/71). Each day of increased TTP multiplied the odds ratio (OR) of survival at 30 days by a factor of 1.32 [95% confidence interval (CI) 1.06–1.69]. Shorter TTP was associated with increased mortality, with 1-day TTP associated with 30-day mortality 37% (41/112) (95%CI: 28%–46%) and 5-day TTP 11% (2/18) (95%CI: 2%–36%).
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1111/J.1469-0691.2009.02802.X
Abstract: Australia-wide population-based surveillance for scedosporiosis identified 180 cases, with 118 (65.6%) cases of colonization and 62 (34.4%) cases of infection. Predisposing factors for isolation of Scedosporium spp. included chronic lung disease in 37.8% and malignancy in 21.7% of cases. Predictors of invasive disease (n=62) included haematological stem cell transplantation (n=7), leukaemia (n=16) and diabetes mellitus (n=8). Of 183 phenotypically-speciated isolates, 75 (41%) were Scedosporium prolificans (risk factors: haematologic cancer (n=17), neutropaenia (n=14)) and 108 (59%) had Scedosporium apiospermum/Pseudallescheria boydii phenotype [risk factor: diabetes (n=15)]. Scedosporium prolificans (p 0.01) and leukaemia (p 0.03) independently predicted death. Epidemiological and antifungal susceptibility profiles of Scedosporium aurantiacum (prevalence>or=15.8%) and S. apiospermum were similar. No patient with S. aurantiacum infection (n=6) died. This is the first description of clinical features associated with S. aurantiacum.
Publisher: Wiley
Date: 05-2006
Publisher: Elsevier BV
Date: 08-2019
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1111/J.1469-0691.2009.02821.X
Abstract: The risk factors for and clinical features of bloodstream infection with uncommon Candida spp. (species other than C. albicans, C. glabrata, C. parapsilosis, C. tropicals and C. krusei) are incompletely defined. To identify clinical variables associated with these species that might guide management, 57 cases of candidaemia resulting from uncommon Candida spp. were analysed in comparison with 517 episodes of Candida albicans candidaemia (2001-2004). Infection with uncommon Candida spp. (5.3% of candidaemia cases), as compared with C. albicans candidaemia, was significantly more likely to be outpatient-acquired than inpatient-acquired (15 of 57 vs. 65 of 517 episodes, p 0.01). Prior exposure to fluconazole was uncommon (n=1). Candida dubliniensis was the commonest species (n=22, 39%), followed by Candida guilliermondii (n=11, 19%) and Candida lusitaniae (n=7, 12%).C. dubliniensis candidaemia was independently associated with recent intravenous drug use (p 0.01) and chronic liver disease (p 0.03), and infection with species other than C. dubliniensis was independently associated with age<65 years (p 0.02), male sex (p 0.03) and human immunodeficiency virus infection (p 0.05). Presence of sepsis at diagnosis and crude 30-day mortality rates were similar for C. dubliniensis-related, non-C. dubliniensis-related and C. albicans-related candidaemia. Haematological malignancy was the commonest predisposing factor in C. guilliermondii (n=3, 27%) and C. lusitaniae (n=3, 43%) candidaemia. The 30-day mortality rate of C. lusitaniae candidaemia was higher than the overall death rate for all uncommon Candida spp. (42.9% vs. 25%, p not significant). All isolates were susceptible to hotericin B, voriconazole, posaconazole, and caspofungin five strains (9%) had fluconazole MIC values of 16-32 mg/L. Candidaemia due to uncommon Candida spp. is emerging among hospital outpatients certain clinical variables may assist in recognition of this entity.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2018
Publisher: Public Library of Science (PLoS)
Date: 14-07-2014
Publisher: American Society of Tropical Medicine and Hygiene
Date: 06-2011
Publisher: Oxford University Press (OUP)
Date: 06-2010
DOI: 10.1086/652440
Abstract: BACKGROUND. In 2001, Australia introduced a unique 7-valent pneumococcal conjugate vaccine (7vPCV) 2-, 4-, and 6-month schedule with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster for Aboriginal children, and in 2005, 7vPCV alone in a 2-, 4-, and 6-month schedule for non-Aboriginal children. Aboriginal adults are offered 23vPPV but coverage is poor. We investigated trends in invasive pneumococcal disease (IPD) in Western Australia (WA). METHODS. Enhanced IPD surveillance has been ongoing since 1996. We calculated IPD incidence rates for Aboriginal and non-Aboriginal Australians before and after introduction of 7vPCV. RESULTS. A total of 1792 cases occurred during the period 1997-2007 the IPD incidence rate was 47 cases per 100,000 population per year among Aboriginal people and 7 cases per 100,000 population per year in non-Aboriginal people. After introduction of 7vPCV, IPD rates among Aboriginal children decreased by 46% for those 30% in non-Aboriginal people 50 years of age but increased among Aboriginal adults (eg, from 59.1 to 109.6 cases per 100,000 population per year among those 30-49 years of age). Although IPD due to 7vPCV serotypes decreased in all age groups, IPD incidence due to non-7vPCV serotypes increased, and it almost doubled among Aboriginal adults 30-49 years of age (from 48.3 to 97.0 cases per 100,000 population per year). Among non-Aboriginal children, 37% of IPD is now due to serotype 19A. CONCLUSIONS. IPD incidence rates have decreased markedly among children and non-Aboriginal adults with a 3-dose infant 7vPCV schedule. However, IPD due to non-7vPCV serotypes has increased and is of particular concern among young Aboriginal adults, for whom an intensive 23vPPV c aign is needed. An immunization register covering all age groups should be established.
Publisher: Wiley
Date: 08-2013
DOI: 10.1111/IMJ.12213
Publisher: Wiley
Date: 16-08-2022
DOI: 10.1111/MYC.13513
Abstract: Antifungal administration via outpatient parenteral antimicrobial therapy (OPAT) is infrequent. As patients with invasive fungal infections (IFIs) receiving OPAT are at high risk of readmissions, careful, risk‐based patient selection and monitoring is important. To describe our experience managing IFIs via OPAT, including assessment of risk factors associated with unplanned readmissions. A retrospective cohort study of outpatients from two tertiary hospitals in Western Australia managed with parenteral antifungals for the treatment of IFIs from 2012 to 2020. Outcomes assessed were unplanned OPAT‐related readmissions adverse events and achievement of treatment aim at the completion of OPAT. Forty‐six patients were included, encompassing 696 OPAT days. Twenty‐three (50%) patients received intravenous (IV) liposomal hotericin B (L‐AmB), 23 (50%) received IV echinocandins and one (2%) patient received IV fluconazole. One patient received both IV L‐AmB and an echinocandin. Unplanned OPAT‐related readmissions occurred in 13 (28%) patients and any adverse event occurred in 19 (41%), most commonly nephrotoxicity amongst patients receiving L‐AmB. On univariate analysis, unplanned OPAT‐related readmissions were more common in Mucorales infection, L‐AmB doses of ≥5 mg/kg and otorhinolaryngologic (ENT) infections. At the completion of OPAT, attainment of treatment aims occurred in 28 (61%) patients. Patients receiving parenteral antifungals via OPAT experience high rates of unplanned readmissions and adverse events. Risk factor identification may facilitate optimal patient selection and establishment of treatment aims.
Publisher: Elsevier BV
Date: 11-2003
DOI: 10.1016/S0732-8893(03)00139-1
Abstract: We report the development and evaluation of a real-time PCR assay using the LightCycler instrument for the detection of C. albicans and A. fumigatus DNA in whole blood. Recently published consensus criteria for the diagnosis of invasive fungal infection (IFI) were used for all patient s les. Unique and published primer pairs were developed and assessed for sensitivity, specificity, and reproducibility to detect C. albicans and A. fumigatus DNA in s les spiked with purified DNA, and whole blood s les from 8 high-risk patients and 45 negative controls. The real-time assay demonstrated an analytical sensitivity of 10 fg of purified C. albicans and A. fumigatus DNA and was found to be specific for each species. The standardized approach was highly reproducible and detected C. albicans and A. fumigatus DNA in two patients with proven IFI and in one patient with a possible IFI. In addition, we report for the first time the use of recently published international consensus criteria for the diagnosis of IFI in the evaluation of a mildly invasive fungal diagnostic assay. Standardized clinical criteria and a more standardized approach to detect fungal DNA in less invasive patient s les, may permit a more reliable comparison of future studies. A rapid real-time detection of fungal DNA in whole blood, combined with standard clinical markers of response, may be more useful for monitoring patients at risk of developing IFI than other diagnostic methods currently available.
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.JHIN.2010.01.026
Abstract: Multi-resistant Pseudomonas aeruginosa (MRPa) has been isolated from patients in a Western Australian teaching hospital with increasing frequency since first encountered in 2006. Between 2006 and 2008 the number of patients with MRPa increased from three to nine per annum, and their location shifted from intensive care to a high dependency unit. A novel water-saving device (aerator) in a staff hand basin was identified as a likely disseminator, with MRPa being isolated from biofilm in the basin's plumbing. The disposal of patient waste, surplus intravenous antibiotic infusions and solid items via hand basins were possible contributory factors. Genotyping of MRPa from patients in other hospitals showed distinct genotypic lineages. The third seasonal cluster persisted for longer, indicating adaption to environment. More effective environmental control of P. aeruginosa is urgently needed.
Publisher: Wiley
Date: 16-11-2021
Publisher: Elsevier BV
Date: 11-2021
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 09-2005
Abstract: We describe 4 cases of Legionella pneumophila serogroup 13-associated pneumonia. These cases originate from a broad geographic range that includes Scotland, Australia, and New Zealand. L. pneumophila serogroup 13 pneumonia has a clinically erse spectrum that ranges from relatively mild, community-acquired pneumonia to potentially fatal severe pneumonia with multisystem organ failure. All cases were confirmed by culture and direct fluorescent antibody staining or indirect immunofluorescent antibody tests. Proven or putative sources of L. pneumophila serogroup 13 infections in 2 patients included a contaminated whirlpool spa filter and river water. An environmental source was not found in the remaining 2 cases environmental cultures yielded only other L. pneumophila serogroups or nonpneumophila Legionella species. We describe the clinical and laboratory features of L. pneumophila serogroup 13 infections. L. pneumophila serogroup 13 pneumonia is rarely reported, but it may be an underrecognized pathogenic serogroup of L. pneumophila.
Publisher: Oxford University Press (OUP)
Date: 09-10-2014
DOI: 10.1093/JAC/DKT402
Abstract: To assess the risk factors for nephrotoxicity caused by vancomycin continuous infusion in a predominantly Caucasian outpatient population. This was a retrospective cohort study of 155 patient episodes from December 2006 to December 2011. Vancomycin-associated nephrotoxicity (VN) occurred in 26 of 155 (17%) patient episodes. After adjustment for baseline renal function, maximum steady-state vancomycin concentrations ≥32 mg/L [OR 8.7 (95% CI 3.1-29.6), P < 0.001] and angiotensin receptor blockade [OR 9.78 (95% CI 3.1-39.4), P < 0.001] were independently associated with VN. The cumulative dose and duration of vancomycin therapy were not independent predictors of VN. Cessation of angiotensin receptor-blocking medications in selected patient groups, enhanced monitoring and establishing target steady-state concentrations <30 mg/L to avoid excessive vancomycin exposure may reduce the risk of VN.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.BURNS.2010.01.005
Abstract: Advances in critical care, operative techniques, early fluid resuscitation, antimicrobials to control bacterial infections, nutritional support to manage the hypermetabolic response and early wound excision and coverage has improved survival rates in major burns patients. These advances in management have been associated with increased recognition of invasive infections caused by Candida species in critically ill burns patients. Candida albicans is the most common species to cause invasive Candida infections, however, non-albicans Candida species appear to becoming more frequent. These later species may be less fluconazole susceptible than Candida albicans. High crude and attributable mortality rates from invasive Candida sepsis are multi-factorial. Diagnosis of invasive candidiasis and candidemia remains difficult. Prophylactic and pre-emptive therapies appear promising strategies, but there is no specific approach which is well-studied and clearly efficacious in high-risk burns patients. Treatment options for invasive candidiasis include several hotericin B formulations and newer less toxic antifungal agents, such as azoles and echinocandins. We review the currently available data on diagnostic and management strategies for invasive candidiasis and candidemia whenever possible providing reference to the high-risk burn patients. We also present an algorithm for the management of candidemia and invasive candidiasis in burn patients.
Publisher: Springer Science and Business Media LLC
Date: 03-03-2014
Publisher: OMICS Publishing Group
Date: 2017
Publisher: Oxford University Press (OUP)
Date: 10-07-2017
DOI: 10.1093/JAC/DKX203
Abstract: Most outpatient parenteral antimicrobial therapy (OPAT) services use a hospital-based model of care in which patients remain in proximity to large hospitals facilitating clinical review. We aimed to evaluate clinical outcomes and complication rates for patients living in geographically isolated locations managed by telemedicine-supported OPAT. Methods: This was a retrospective cohort study. Between 2011 and 2015, we delivered 88 episodes of care involving 83 adult patients resulting in 2261 days of OPAT. The median age was 56 years, 8 of 83 (10%) were indigenous Australian and the median Charlson comorbidity index score was 2 (IQR 1-4). The median distance of patients' residence from our hospital was 288 km (IQR 201-715) and the median duration on the programme was 26 days (IQR 14-34). Bone and joint infections accounted for 75% of infections treated. Favourable clinical outcomes (improvement or cure) were achieved in 87% of patients and the unplanned, OPAT-related readmission rate was 8%. Nineteen percent and 10% of patients had drug-related and line-related adverse effects, respectively. Despite a complex case mix, our adverse event and readmission rates are similar to the published literature describing a non-telemedicine model to deliver OPAT. High rates of favourable clinical outcomes and likely cost benefits suggest that telemedicine-supported OPAT is an efficacious and safe substitute for inpatient care in our setting.
Publisher: Oxford University Press (OUP)
Date: 07-2002
DOI: 10.1086/341087
Abstract: This international collaborative survey identified culture-confirmed legionellosis in 508 patients with sporadic community-acquired legionellosis. Legionella pneumophila constituted 91.5% of the isolates. Serogroup 1 was the predominant serogroup (84.2%), and serogroups 2-13 (7.4%) accounted for the remaining serogroups. The Legionella species most commonly isolated were L. longbeachae (3.9%) and L. bozemanii (2.4%), followed by L. micdadei, L. dumoffii, L. feeleii, L. wadsworthii, and L. anisa (2.2% combined). L. longbeachae constituted 30.4% of the community-acquired Legionella isolates in Australia and New Zealand.
Publisher: Oxford University Press (OUP)
Date: 13-02-2017
DOI: 10.1093/JAC/DKX047
Publisher: SAGE Publications
Date: 09-2016
Publisher: Springer Science and Business Media LLC
Date: 03-04-2001
DOI: 10.1007/PL00011252
Abstract: Reported here is a case of cerebral Mycobacterium avium complex infection that occurred in an HIV-infected patient, who had been treated for disseminated infection and had discontinued clarithromycin and ethambutol following a significant rise in his CD4+ T-cell count after starting highly active antiretroviral therapy. He responded well to excision of the lesion and reinstitution of multidrug therapy. Caution should be exercised when considering ceasing maintenance therapy for disseminated Mycobacterium avium complex infection in HIV-infected patients who demonstrate an apparently good immunologic response to highly active antiretroviral therapy, as this response may not necessarily restore protective immunity against all opportunistic pathogens.
Publisher: AMPCo
Date: 1996
Publisher: Oxford University Press (OUP)
Date: 08-2008
DOI: 10.1086/589754
Abstract: Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.
Publisher: AMPCo
Date: 2003
Publisher: Wiley
Date: 19-05-2015
DOI: 10.1111/TID.12377
Abstract: Penicillium marneffei is a thermally dimorphic fungus that can cause severe opportunistic infections in endemic regions of Southeast Asia, particularly in in iduals infected with human immunodeficiency virus-1, but has rarely been reported in solid organ transplant recipients. Herein, we report the first case, to our knowledge, of P. marneffei infection in a lung transplant recipient, occurring in a 41-year-old woman 28 months post lung transplantation, after recent travel to Vietnam. We have reviewed the literature to derive some management principles for this rare infection in this clinical context. The number of P. marneffei infections in transplant recipients may increase, as a result of increasing rates of transplantation and travel to endemic areas.
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/J.JHIN.2003.10.009
Abstract: The aim of this study was to document the evolution of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia at teaching hospitals in Perth, Western Australia (WA), and determine the risk factors and outcomes of the disease. We performed a retrospective case series analysis of all laboratory-confirmed episodes of S. aureus bacteraemia at Perth teaching hospitals between 1 July 1997 and 30 June 1999 by linking laboratory data with hospitalization data from the state's Hospital Morbidity Data System. Episodes of S. aureus bacteraemia were stratified according to methicillin susceptibility and the relationship between methicillin resistance and key factors or outcomes was determined. Almost 11% of episodes of S. aureus bacteraemia (55/509) were caused by MRSA. On age-adjusted multivariate analysis, Aboriginality (RR 6.71, 95% CI 3.20-14.10, P<0.001), geriatric unit admission (RR 5.74, 95% CI 2.01-16.37, P=0.001), female sex (RR 1.88, 95% CI 1.03-3.42, P=0.04) and healthcare-associated disease (RR 1.93, 95% CI 1.01-3.70, P=0.05) were independently associated with MRSA bacteraemia. Outcomes among those with MRSA bacteraemia included death in 15 patients and re-admission for an MRSA-related complication in five. Empirical use of vancomycin needs consideration in at-risk patients in whom Gram-positive bacteraemia is suspected clinically, with prompt review of therapy once antibiotic susceptibility results are known. The rates of re-admission after discharge for MRSA bacteraemia could be used as a clinical indicator to monitor the quality of care in hospitals.
Publisher: Springer Science and Business Media LLC
Date: 04-1996
DOI: 10.1007/BF01695659
Abstract: A 24 GHz highly-linear upconversion mixer, based on a duplex transconductance path (DTP), is proposed for automotive short-range radar sensor applications using the 65-nm CMOS process. A mixer with an enhanced transconductance stage consisting of a DTP is presented to improve linearity. The main transconductance path (MTP) of the DTP includes a common source (CS) lifier, while the secondary transconductance path (STP) of the DTP is implemented as an improved cross-quad transconductor (ICQT). Two inductors with a bypass capacitor are connected at the common nodes of the transconductance stage and switching stage of the mixer, which acts as a resonator and helps to improve the gain and isolation of the designed mixer. According to the measured results, at 24 GHz the proposed mixer shows that the linearity of output 1-dB compression point (OP
Publisher: SAGE Publications
Date: 09-2003
DOI: 10.1177/089686080302300511
Abstract: The International Society for Peritoneal Dialysis (ISPD) guidelines recommend empiric therapy with cefazolin and ceftazidime for peritoneal dialysis (PD)-related peritonitis. Empiric cefazolin therapy may have diminishing efficacy because of emerging methicillin resistance in gram-positive bacteria (GPB). Western Australia also has large numbers of Aboriginal and isolated regional patients, where giving these antimicrobials can be impractical. To evaluate, based on local antimicrobial resistance patterns, the feasibility of following ISPD guidelines in Western Australia and to identify any subgroups of PD peritonitis patients that may benefit from alternative empiric intraperitoneal antibiotics ( e.g., vancomycin). Retrospective study of all PD peritonitis episodes in Western Australia from 1 February 2000 to 31 January 2001. Three adult tertiary referral university hospitals and their PD patients in metropolitan Perth and regional Western Australia. All adults on PD in Western Australia. Isolates and antibiograms were analyzed versus patient characteristics, including race and patient demographics. 293 patients (28% Aborigines, 32% regional patients) received PD. 145 episodes of PD peritonitis occurred during the study. The overall PD peritonitis rate was 1 episode/16 patient months, with Aborigines having 1 episode/10.5 patient months versus non-Aborigines having 1 episode/17 patient months p ( 0.001). 36% of isolates from PD peritonitis episodes were resistant to cefazolin or ceftazidime. 22% were methicillin-resistant GPB (MR-GPB) [18% coagulase-negative staphylococci (CoNS), 1.6% MR Staphylococcus aureus] 2.5% were multidrug-resistant gram-negative bacteria (MDR-GNB) 5.7% were polymicrobial (MR-GPB and/or MDR-GNB) and 5.7% were fungal. 63% of CoNS were methicillin resistant. Non-Aboriginal patients yielded MR-GPB in 22% of isolates versus 23% in Aborigines ( p = 0.9). Six of seven cases of fungal peritonitis occurred inAboriginal patients ( p 0.001). In our study population the ISPD guidelines were appropriate for 64% of patients with PD peritonitis. We could not identify specific patient subgroups where empiric cefazolin use could be more effective. High proportions of MR-GPB PD peritonitis episodes, along with local factors, make empiric cefazolin unsuitable for many regional PD patients in Western Australia.
Publisher: Elsevier BV
Date: 2001
Publisher: Georg Thieme Verlag KG
Date: 15-04-2009
Abstract: Candidemia in the pediatric burn population poses a management dilemma due to the paucity of good clinical data to guide treatment decisions. Whilst candidemia is less common than bacteremia in pediatric burns patients, it is associated with significant morbidity and mortality. We report a case of candidemia in an infant with 40% burns with ophthalmic complications secondary to nappy rash. We review the investigation and management of ocular candidemia.
Publisher: AMPCo
Date: 10-2003
Publisher: Springer Science and Business Media LLC
Date: 2009
DOI: 10.1186/CC7964
Publisher: Wiley
Date: 10-1998
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.CMI.2016.01.005
Abstract: Mucormycosis is the second most common cause of invasive mould infection and causes disease in erse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8 87.5% versus 10/66 15.2% p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2-481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3-25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3-13.8). Most deaths occurred within one month. Thereafter we observed ergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome.
Publisher: AMPCo
Date: 05-2001
Publisher: Elsevier BV
Date: 11-2021
Publisher: Oxford University Press (OUP)
Date: 05-06-2012
DOI: 10.1093/CID/CIS529
Abstract: Longer-term morbidity and outcomes of Cryptococcus gattii infection are not described. We analyzed clinical, microbiological, and outcome data in Australian patients followed for 12 months, to identify prognostic determinants. Culture-confirmed C. gattii cases from 2000 to 2007 were retrospectively evaluated. Clinical, microbiological, radiological, and outcome data were recorded at diagnosis and at 6 weeks, 6 months, and 12 months. Clinical and laboratory variables associated with mortality and with death and/or neurological sequelae were determined. Annual C. gattii infection incidence was 0.61 per 10(6) population. Sixty-two of 86 (72%) patients had no immunocompromise 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia, and 1 had human immunodeficiency virus/AIDS. Clinical and microbiological characteristics of infection were similar in immunocompromised and healthy hosts. Isolated lung, combined lung and central nervous system (CNS), and CNS only disease was reported in 12%, 51% and 34% of the cases, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27% 6% developed during therapy) and immune reconstitutionlike syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titers in CNS disease were 563.9 (vs 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. An initial cerebrospinal fluid CRAG titer of ≥256 predicted death and/or neurological sequelae (P = .05). Neurological C. gattii disease predominates in the Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titers are ≥512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important because host immunocompromise is associated with reduced survival.
Publisher: Oxford University Press (OUP)
Date: 06-10-2014
DOI: 10.1093/MMY/MYU054
Abstract: Cutaneous disease is the third most frequent manifestation of mucormycosis. The clinical manifestations of and subsequent mortality due to cutaneous mucormycosis are dependent on the mode of acquisition and the host immune status. Here, we describe the epidemiology, clinical presentation, microbiology, and outcomes of 16 cutaneous mucormycosis infections managed in an Australian tertiary hospital over a 15-year period. The proportion with localized (56%), deep (38%), and disseminated (6%) cutaneous disease as well as the overall mortality (25%) were consistent with findings reported in the published literature. Two novel forms of hospital-acquired infection were reported following a sacral pressure sore and insertion of a foreign body during a bone graft procedure. The majority of patients were immunocompetent (75%) and/or suffered trauma (56%) with associated environmental contamination. A novel finding was that motor vehicle accidents (MVAs) accounted for 78% of all trauma-related cases, suggesting MVAs should receive greater recognition as a potential precipitant of cutaneous mucormycosis. Aggressive decontamination and debridement of devitalized tissue following trauma is therefore likely to play an important role in the prevention of this rare but potentially devastating infection.
Publisher: Elsevier BV
Date: 10-2003
DOI: 10.1016/S0732-8893(03)00129-9
Abstract: A quantitative real-time PCR targeting the Pneumolysin (ply) gene of Streptococcus pneumoniae was developed for the LightCycler instrument using Fluorescence Resonance Energy Transfer (FRET) probes. All common S. pneumoniae serotypes were detected while other bacteria and viruses were not. The sensitivity was determined to be between one and ten target copies per reaction. The PCR was applied to six CSF and 16 whole blood specimens from 17 patients with laboratory proven invasive pneumococcal disease. One hundred percent of CSF specimens and 69% of whole blood specimens were PCR positive. The bacterial loads were determined to be 7.6 to 6.01 x 10(5) copies/microL for the six CSF specimens, and 0.08 to 5.4 x 10(2) copies/microL for the 16 whole blood specimens. Ninety-seven percent of 30 culture and Gram's stain negative CSF specimens and 100% of 50 normal whole blood specimens were PCR negative. This highly sensitive and specific PCR assay has the potential to provide sufficiently rapid results to improve antibiotic treatment of S.pneumoniae infections, while bacterial load quantitation has opened up exciting possibilities for patient management.
Publisher: Elsevier BV
Date: 10-2019
Publisher: Elsevier BV
Date: 11-2023
Publisher: Cold Spring Harbor Laboratory
Date: 07-01-2020
DOI: 10.1101/2020.01.06.896548
Abstract: Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (Clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in over 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades Clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single healthcare facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 339 years outbreak-causing clusters from Clades I, III, and IV originated 34-35 years ago. We observed high rates of antifungal resistance in Clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in Clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris . In less than a decade, C. auris has emerged in healthcare settings worldwide this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.
Publisher: AMPCo
Date: 04-2010
DOI: 10.5694/J.1326-5377.2010.TB03569.X
Abstract: A 19-year-old Sudanese woman, who had lived for about a decade in Ugandan refugee c s, was referred for investigation of a 12-month history of a generalised rash. Two months later, her condition had deteriorated to include cachexia and drowsiness. Despite initial negative findings on investigation, human African trypanosomiasis (HAT) was suspected, and parasites were found in a double-centrifuged s le of cerebrospinal fluid. Eflornithine, the appropriate drug for treatment of late-stage disease, was obtained through the World Health Organization. This case highlights the diagnostic and therapeutic difficulties in managing late-stage HAT in a non-endemic country.
Publisher: Elsevier
Date: 2018
Publisher: Oxford University Press (OUP)
Date: 08-11-2016
DOI: 10.1093/JAC/DKW422
Abstract: Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia. These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™. A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance. We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.
Publisher: Wiley
Date: 08-2000
Publisher: Wiley
Date: 26-03-2001
Publisher: Elsevier BV
Date: 07-2009
Publisher: Oxford University Press (OUP)
Date: 22-05-2013
DOI: 10.1093/CID/CIT341
Abstract: We describe antifungal therapy and management of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least 12 months. Patient data from culture-confirmed cases (2000-2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months. Clinical, laboratory, and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution inflammatory syndrome (IRIS) were determined. Seven of 10 patients with lung infection received hotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC] for a median of 2 weeks) median duration of therapy including azole eradication therapy was 41 weeks, with a complete artial clinical response in 78%. For neurologic disease, 88% of patients received AMB, 78% with 5-FC, for a median of 6 weeks. The median total course was 18 months. Nine patients receiving fluconazole induction therapy were reinduced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurologic sequelae and/or death at 12 months (both P = .02) cerebrospinal fluid drains/shunts were placed in 58% of patients and in 64% of 22 patients with hydrocephalus. IRIS developed 2-12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation, and higher median CD4 counts (all P < .05) corticosteroids reduced cryptococcoma-associated edema. Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.
Publisher: Springer Science and Business Media LLC
Date: 31-05-2020
DOI: 10.1186/S12974-020-01832-2
Abstract: Production of inflammatory mediators by reactive microglial cells in the brain is generally considered the primary mechanism underlying the development of symptoms of sickness in response to systemic inflammation. Depletion of microglia was achieved in C57BL/6 mice by chronic oral administration of PLX5622, a specific antagonist of colony stimulating factor-1 receptor, and in rats by a knock-in model in which the diphtheria toxin receptor was expressed under the control of the endogenous fractalkine receptor (CX3CR1) promoter sequence. After successful microglia depletion, mice and rats were injected with a sickness-inducing dose of lipopolysaccharide according to a 2 (depletion vs. control) × 2 (LPS vs. saline) factorial design. Sickness was measured by body weight loss and decreased locomotor activity in rats and mice, and reduced voluntary wheel running in mice. Chronic administration of PLX5622 in mice and administration of diphtheria toxin to knock-in rats depleted microglia and peripheral tissue macrophages. However, it did not abrogate the inducible expression of proinflammatory cytokines in the brain in response to LPS and even exacerbated it for some of the cytokines. In accordance with these neuroimmune effects, LPS-induced sickness was not abrogated, rather it was exacerbated when measured by running wheel activity in mice. These findings reveal that the sickness-inducing effects of acute inflammation can develop independently of microglia activation.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.IJANTIMICAG.2016.07.005
Abstract: Antifungal susceptibilities of non-Aspergillus filamentous fungal pathogens cannot always be inferred from their identification. Here we determined, using the Sensititre(®) YeastOne(®) YO10 panel, the in vitro activities of nine antifungal agents against 52 clinical isolates of emergent non-Aspergillus moulds representing 17 fungal groups in Australia. Isolates comprised Mucorales (n = 14), Scedosporium/Lomentospora spp. (n = 18) and a range of hyaline hyphomycetes (n = 9) and other dematiaceous fungi (n = 11). Excluding Verruconis gallopava, echinocandins demonstrated poor activity (MICs generally >8 mg/L) against these moulds. Lomentospora prolificans (n = 4) and Fusarium spp. (n = 6) demonstrated raised MICs to all antifungal drugs tested, with the lowest being to voriconazole and hotericin B (AmB), respectively (geometric mean MICs of 3.4 mg/L and 2.2 mg/L, respectively). All Scedosporium apiospermum complex isolates (n = 14) were inhibited by voriconazole concentrations of ≤0.25 mg/L, followed by posaconazole and itraconazole at ≤1 mg/L. Posaconazole and AmB were the most active agents against the Mucorales, with MIC90 values of 1 mg/L and 2 mg/L, respectively, for Rhizopus spp. For dematiaceous fungi, all isolates were inhibited by itraconazole and posaconazole concentrations of ≤0.5 mg/L (MIC90, 0.12 mg/L and 0.25 mg/L, respectively), but voriconazole and AmB also had in vitro activity (MIC90, 0.5 mg/L and 1 mg/L, respectively). Differences in antifungal susceptibility within species and between species within genera support the need for testing in idual patient isolates to guide therapy. The Sensititre(®) YeastOne(®) offers a practical alternative to the reference methodology for susceptibility testing of moulds.
Publisher: American Society for Microbiology
Date: 05-2008
DOI: 10.1128/AAC.01388-07
Abstract: The efficacy of voriconazole in 107 patients with scedosporiosis was analyzed. Principal infection sites were the lungs/sinuses (24%), central nervous system (CNS) (20%), and bone (18%), while 21% of patients had disseminated infection. Solid organ transplantation (22%), hematological malignancy (21%), and surgery/trauma (15%) were the predominant underlying conditions. A successful therapeutic response was achieved in 57% of patients (median, 103 therapy days), with % of those responding receiving ≥28 days of therapy. Patients receiving primary therapy showed a 61% response versus 56% for the others. The best therapeutic responses were seen for skin/subcutaneous (91%) or bone (79%) infections, and the lowest for CNS infections (43%). Patients without major immune suppression (72%) or those with solid organ transplantation (63%) or various hematological conditions (60%) showed the best responses by underlying condition. Median known survival time was 133 days (therapy successes, 252 days failures, 21 days). In all, 43 (40%) patients died, 73% due to scedosporiosis. Patients with Scedosporium prolificans infection had significantly reduced survival times ( P = 0.0259) and were more likely to die from fungal infection ( P = 0.002) than were Scedosporium apiospermum -infected patients. In a subset of 43 patients where voriconazole baseline MICs were available, response to voriconazole was higher for S. apiospermum -infected patients (54% response MIC 50 , 0.25 μg/ml) than for S. prolificans -infected patients (40% response MIC 50 , 4.0 μg/ml). Voriconazole demonstrated clinically useful activity in the treatment of both S. apiospermum and S. prolificans infections and was well tolerated.
Publisher: AMPCo
Date: 12-2006
DOI: 10.5694/J.1326-5377.2006.TB00723.X
Abstract: To describe the clinical features and management of African migrants recently arrived in Western Australia and subsequently diagnosed with malaria. Retrospective case record analysis of African migrants aged > or = 16 years with malaria referred to Royal Perth Hospital (RPH) from the WA Migrant Health Unit (MHU) between 1 March 2003 and 30 September 2005. Demographic variables clinical and laboratory variables Plasmodium species antimalarial medications used and their efficacy. 57 (3.5%) of 1609 adult African migrants screened at the MHU were diagnosed with malaria and referred for treatment. 52 were infected with P. falciparum, two with P. ovale, one with P. malariae, and one with both P. falciparum and P. malariae the malaria parasite could not be identified in one in idual. No patients had severe malaria by World Health Organization criteria. Most patients (53/57) were treated as outpatients with oral antimalarial therapy four patients without severe malaria were admitted to hospital for treatment and observation. Atovaquone-proguanil was the antimalarial medication most commonly used (in 52/57), and treatment was well tolerated in most patients. Post-treatment follow-up was possible in 50 patients all 27 of those who were followed for 4 weeks or longer were cured. Cure could not be concluded in patients with shorter follow-up periods. All follow-up blood films were negative for malarial parasites. Outpatient treatment of malaria in recently arrived adult African migrants appeared to be safe and efficacious in our cohort.
Publisher: Cambridge University Press (CUP)
Date: 05-2004
DOI: 10.1086/502410
Abstract: To demonstrate that nosocomial transmission of vancomycin-resistant enterococci (VRE) can be terminated and endemicity prevented despite widespread dissemination of an epidemic strain in a large tertiary-care referral hospital. Two months after the index case was detected in the intensive care unit, 68 patients became either infected or colonized with an epidemic strain of vanB vancomycin-resistant Enterococcus faecium despite standard infection control procedures. The following additional interventions were then introduced to control the outbreak: (1) formation of a VRE executive group (2) rapid laboratory identification (30 to 48 hours) using culture and polymerase chain reaction detection of van A and vanB resistance genes (3) mass screening of all hospitalized patients with isolation of carriers and cohorting of contacts (4) environmental screening and increased cleaning (5) electronic flagging of medical records of contacts and (6) antibiotic restrictions (third-generation cephalosporins and vancomycin). A total of 19,658 patient and 24,396 environmental swabs were processed between July and December 2001. One hundred sixty-nine patients in 23 wards were colonized with a single strain of vanB vancomycin-resistant E. faecium. Introducing additional control measures rapidly brought the outbreak under control. Hospital-wide screening found 39 previously unidentified colonized patients, with only 7 more nonsegregat-ed patients being detected in the next 2 months. The outbreak was terminated within 3 months at a cost of $2.7 million (Australian dollars). Despite widespread dissemination of VRE in a large acute care facility, eradication was achievable by a well-resourced, coordinated, multifaceted approach and was in accordance with good clinical governance.
Publisher: Wiley
Date: 04-2004
Publisher: Oxford University Press (OUP)
Date: 05-2020
DOI: 10.1093/OFID/OFAA158
Abstract: Whole-genome sequencing clustered Australian Candida auris isolates from sporadic cases within clade III. Case isolates were genomically distinct however, unexpectedly, those from 1 case comprised 2 groups separated by & single nucleotide polymorphisms (SNPs) with no isolate being identical, in contrast to outbreaks where isolates from any 1 in idual have differed by & SNPs. Multidrug resistance was absent. High within-host genetic heterogeneity should be considered when investigating C. auris infections.
Publisher: Springer Science and Business Media LLC
Date: 09-01-2015
Publisher: Frontiers Media SA
Date: 27-12-2021
DOI: 10.3389/FCIMB.2021.761596
Abstract: Scedosporium spp. are the second most prevalent filamentous fungi after Aspergillus spp. recovered from cystic fibrosis (CF) patients in various regions of the world. Although invasive infection is uncommon prior to lung transplantation, fungal colonization may be a risk factor for invasive disease with attendant high mortality post-transplantation. Abundant in the environment, Scedosporium aurantiacum has emerged as an important fungal pathogen in a range of clinical settings. To investigate the population genetic structure of S. aurantiacum , a MultiLocus Sequence Typing (MLST) scheme was developed, screening 24 genetic loci for polymorphisms on a tester strain set. The six most polymorphic loci were selected to form the S. aurantiacum MLST scheme: actin ( ACT ), calmodulin ( CAL ), elongation factor-1α ( EF1 α), RNA polymerase subunit II ( RPB2 ), manganese superoxide dismutase ( SOD2 ), and β-tubulin ( TUB ). Among 188 global clinical, veterinary, and environmental strains, 5 to 18 variable sites per locus were revealed, resulting in 8 to 23 alleles per locus. MLST analysis observed a markedly high genetic ersity, reflected by 159 unique sequence types. Network analysis revealed a separation between Australian and non-Australian strains. Phylogenetic analysis showed two major clusters, indicating correlation with geographic origin. Linkage disequilibrium analysis revealed evidence of recombination. There was no clustering according to the source of the strains: clinical, veterinary, or environmental. The high ersity, especially amongst the Australian strains, suggests that S. aurantiacum may have originated within the Australian continent and was subsequently dispersed to other regions, as shown by the close phylogenetic relationships between some of the Australian sequence types and those found in other parts of the world. The MLST data are accessible at mlst.mycologylab.org . This is a joined publication of the ISHAM/ECMM working groups on “ Scedosporium/Pseudallescheria Infections” and “Fungal Respiratory Infections in Cystic Fibrosis”.
Publisher: Cold Spring Harbor Laboratory
Date: 29-10-2021
DOI: 10.1101/2021.10.22.465535
Abstract: We determined hotericin B (AmB) susceptibility and sequenced key genes of the ergosterol biosynthesis pathway implicated in AmB resistance ( ERG2, ERG3, ERG6, ERG11 ) of 321 clinical isolates of Candida auris . In antifungal susceptibility testing, 19 (5.9%) isolates were categorized as AmB-resistant (MIC ≥2 mg/l). Only one AmB-resistant isolate presented a unique non-wild-type ERG6 genotype that was confirmed to confer hotericin B resistance (MIC mg/l) when introduced into a susceptible strain (MIC = 0.5 mg/l).
Publisher: Oxford University Press (OUP)
Date: 23-09-2009
DOI: 10.1093/QJMED/HCP129
No related grants have been discovered for Christopher Heath.