ORCID Profile
0000-0002-5957-4178
Current Organisation
SA Pathology
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
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: 17-04-2015
DOI: 10.1111/MYC.12324
Abstract: The emergence of triazole resistance, including multi-triazole-resistant Aspergillus fumigatus is being reported around the world, but there has been little evidence of this problem to date in Australia. Here we describe a retrospective search of antifungal susceptibility results of all Australian clinical A. fumigatus isolates referred to the National Mycology Reference Centre, Adelaide, Australia between 2000 and 2013, yielding 13 isolates with elevated minimum inhibitory concentrations to itraconazole, posaconazole and/or voriconazole. Four isolates were found to be Aspergillus lentulus, a closely related, morphologically similar species known to have reduced susceptibility to triazoles. Analysis of the cyp51A gene of nine confirmed A. fumigatus isolates revealed two carrying the TR34 /L98H mutation, one apparently locally acquired in 2004, and the other probably acquired abroad in 2012. Four isolates possessed the G54R, F46Y, Y431S and G448S mutations, respectively, whereas three isolates did not possess known cyp51A resistance mutations, raising the possibility of other, undetected resistance mechanisms. Routine antifungal susceptibility testing is definitively recommended in patients on long term and sub-therapeutic triazole therapy with breakthrough Aspergillus infection and recommended for all clinically relevant A. fumigatus isolates.
Publisher: American Public Health Association
Date: 2019
Publisher: Oxford University Press
Date: 12-2017
DOI: 10.1093/MED/9780198755388.003.0012
Abstract: Cryptococcus neoformans and Cryptococcus gattii are the principal pathogenic species within the genus Cryptococcus and the causative agents of cryptococcosis. Although rare, the incidence of infection due to other Cryptococcus species previously regarded as saprophytes, has increased over the last 40 years. Irrespective of the infecting species, infections are acquired following inhalation from the environment, causing localised or disseminated disease. The severity of disease is dependent on the organism’s virulence factors and the host’s immune response, and the clinical manifestations are indistinguishable. Accurate identification of the pathogenic species relies on rDNA sequencing
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 2007
Abstract: Recent Cryptococcus gattii infections in humans and animals without travel history to Vancouver Island, as well as environmental isolations of the organism in other areas of the Pacific Northwest, led to an investigation of potential dispersal mechanisms. Longitudinal analysis of C. gattii presence in trees and soil showed patterns of permanent, intermittent, and transient colonization, reflecting C. gattii population dynamics once the pathogen is introduced to a new site. Systematic s ling showed C. gattii was associated with high-traffic locations. In addition, C. gattii was isolated from the wheel wells of vehicles on Vancouver Island and the mainland and on footwear, consistent with anthropogenic dispersal of the organism. Increased levels of airborne C. gattii were detected during forestry and municipal activities such as wood chipping, the byproducts of which are frequently used in park landscaping. C. gattii dispersal by these mechanisms may be a useful model for other emerging pathogens.
Publisher: American Society for Microbiology
Date: 06-2012
DOI: 10.1128/AAC.06252-11
Abstract: Clinical breakpoints (CBPs) are not available for the Cryptococcus neoformans-Cryptococcus gattii species complex. MIC distributions were constructed for the wild type (WT) to establish epidemiologic cutoff values (ECVs) for C. neoformans and C. gattii versus hotericin B and flucytosine. A total of 3,590 hotericin B and 3,045 flucytosine CLSI MICs for C. neoformans (including 1,002 VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs for C. gattii , respectively (including 42 to 259 VGI, VGII, VGIII, and VGIV isolates), were gathered in 9 to 16 ( hotericin B) and 8 to 13 (flucytosine) laboratories (Europe, United States, Australia, Brazil, Canada, India, and South Africa) and aggregated for the analyses. Additionally, 442 hotericin B and 313 flucytosine MICs measured by using CLSI-YNB medium instead of CLSI-RPMI medium and 237 Etest hotericin B MICs for C. neoformans were evaluated. CLSI-RPMI ECVs for distributions originating in ≥3 laboratories (with the percentages of isolates for which MICs were less than or equal to ECVs given in parentheses) were as follows: for hotericin B, 0.5 μg/ml for C. neoformans VNI (97.2%) and C. gattii VGI and VGIIa (99.2 and 97.5%, respectively) and 1 μg/ml for C. neoformans (98.5%) and C. gattii nontyped (100%) and VGII (99.2%) isolates for flucytosine, 4 μg/ml for C. gattii nontyped (96.4%) and VGI (95.7%) isolates, 8 μg/ml for VNI (96.6%) isolates, and 16 μg/ml for C. neoformans nontyped (98.6%) and C. gattii VGII (97.1%) isolates. Other molecular types had apparent variations in MIC distributions, but the number of laboratories contributing data was too low to allow us to ascertain that the differences were due to factors other than assay variation. ECVs may aid in the detection of isolates with acquired resistance mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 11-2006
DOI: 10.1007/S11046-006-0066-1
Abstract: Cryptococcus neoformans and Cryptococcus gattii are etiologic agents of cryptococcal pneumonia and meningitis, potentially lethal syndromes associated with AIDS. A related species, Cryptococcus laurentii, has recently been implicated in several cases of human disease. Guano from Canada Goose (Branta canadensis), an organism that lives closely beside man and inhabits recreational space in rural and suburban areas, might be a significant environmental reservoir of Cryptococcus organisms in non-urban areas. Cryptococcal organisms were isolated from Canada Goose guano from a site in rural northern New York, with identification based upon colony and microscopic morphology, ability to metabolize L: -Dopa to melanin, and positive reaction with a commercial anti-cryptococcal capsular polysaccharide latex bead agglutination test. DNA sequences from five positive isolates were identical to each other, and identical to the ITS1-5.8S-ITS2 sequences of C. laurentii strain CBS7140 (Accession AY315665) across a 511 bp sequence. All five isolates of C. laurentii possess three of the known virulence factors common to cryptococcal organisms that cause human disease: capsule, ability to grow at 37 degrees C, and laccase activity.
Publisher: Wiley
Date: 11-12-2021
DOI: 10.1111/MYC.13211
Publisher: American Public Health Association
Date: 2019
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: Frontiers Media SA
Date: 14-01-2020
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 2007
Abstract: Cryptococcus gattii, emergent on Vancouver Island, British Columbia (BC), Canada, in 1999, was detected during 2003-2005 in 3 persons and 8 animals that did not travel to Vancouver Island during the incubation period positive environmental s les were detected in areas outside Vancouver Island. All clinical and environmental isolates found in BC were genotypically consistent with Vancouver Island strains. In addition, local acquisition was detected in 3 cats in Washington and 2 persons in Oregon. The molecular profiles of Oregon isolates differed from those found in BC and Washington. Although some microclimates of the Pacific Northwest are similar to those on Vancouver Island, C. gattii concentrations in off-island environments were typically lower, and human cases without Vancouver Island contact have not continued to occur. This suggests that C. gattii may not be permanently colonized in off-island locations.
Publisher: American Society for Microbiology
Date: 11-2015
DOI: 10.1128/AAC.01250-15
Abstract: Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans , 186 C. dubliniensis , 3,188 C. glabrata complex, 119 C. guilliermondii , 493 C. krusei , 205 C. lusitaniae , 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 μg/ml for C. albicans , 0.12, 0.25, and 0.03 μg/ml for C. glabrata complex, 4, 2, and 4 μg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 μg/ml for C. tropicalis , 0.25, 1, and 0.25 μg/ml for C. krusei , 0.25, 1, and 0.12 μg/ml for C. lusitaniae , 4, 2, and 2 μg/ml for C. guilliermondii , and 0.25, 0.25, and 0.12 μg/ml for C. dubliniensis . Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended.
Publisher: American Society for Microbiology
Date: 2019
DOI: 10.1128/AAC.01651-18
Abstract: Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans , 215 C. dubliniensis , 4,418 C. glabrata species complex, 157 C. guilliermondii ( Meyerozyma guilliermondii ), 676 C. krusei ( Pichia kudriavzevii ), 298 C. lusitaniae ( Clavispora lusitaniae ), 911 C. parapsilosis sensu stricto , 3,691 C. parapsilosis species complex, 36 C. metapsilosis , 110 C. orthopsilosis , 1,854 C. tropicalis , 244 Saccharomyces cerevisiae , 1,409 Aspergillus fumigatus , 389 A. flavus , 130 A. nidulans , 233 A. niger , and 302 A. terreus complex isolates.
Publisher: Proceedings of the National Academy of Sciences
Date: 30-11-2004
Abstract: Cryptococcus gattii causes life-threatening infection of the pulmonary and central nervous systems in hosts with normal immunity and traditionally has been considered to be restricted geographically to tropical and subtropical climates. The recent outbreak of C. gattii in the temperate climate of Vancouver Island, BC, Canada, led to a collaborative investigation. The objectives of the current study were to ascertain the environmental source of the outbreak infections, survey the molecular types of the outbreak and environmental cryptococcal isolates, and determine the extent of genetic ersity among the isolates. PCR-fingerprinting and lified fragment length polymorphism (AFLP) were used to examine the genotypes, and mating assays were performed to determine the mating type of the isolates. All outbreak and environmental isolates belonged to C. gattii . Concordant results were obtained by using PCR-fingerprinting and AFLP analysis. The vast majority of clinical and veterinary infections were caused by isolates of the molecular type VGII/AFLP6, but two were caused by molecular type VGI/AFLP4. All environmental isolates belonged to molecular type VGII/AFLP6. Two or three subtypes were observed within VGII/AFLP6 among outbreak and environmental isolates. All mating-competent isolates were of the α-mating type. The emergence of this usually tropical pathogen on Vancouver Island highlights the changing distribution of this genotype and emphasizes the importance of an ongoing collaborative effort to monitor the global epidemiology of this yeast.
Publisher: Informa UK Limited
Date: 06-10-2023
Publisher: Wiley
Date: 11-2021
DOI: 10.1111/IMJ.15586
Abstract: Invasive fungal diseases (IFD) are serious infections associated with high mortality, particularly in immunocompromised patients. The prescribing of antifungal agents to prevent and treat IFD is associated with substantial economic burden on the health system, high rates of adverse drug reactions, significant drug–drug interactions and the emergence of antifungal resistance. As the population at risk of IFD continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ antifungal stewardship (AFS) programmes and measures to monitor and prevent infection has become increasingly important. These guidelines outline the essential components, key interventions and metrics, which can help guide implementation of an AFS programme in order to optimise antifungal prescribing and IFD management. Specific recommendations are provided for quality processes for the prevention of IFD in the setting of outbreaks, during hospital building works, and in the context of Candida auris infection. Recommendations are detailed for the implementation of IFD surveillance to enhance detection of outbreaks, evaluate infection prevention and prophylaxis interventions and to allow benchmarking between hospitals. Areas in which information is still lacking and further research is required are also highlighted.
Publisher: Springer Science and Business Media LLC
Date: 2008
DOI: 10.1007/S11908-008-0011-1
Abstract: An unprecedented emergence of cryptococcal infections in animals and otherwise healthy humans was recognized in 1999 on the east coast of Vancouver Island, British Columbia. Unexpectedly, these infections were caused by Cryptococcus gattii, a species closely related to the AIDS-associated fungal pathogen Cryptococcus neoformans. Human cases have continued over the past 8 years and now total approximately 170 with eight deaths. Extensive environmental s ling, coupled with detailed molecular typing of isolates, revealed areas of permanent and transient colonization with primarily three genotypes of the fungus. C. gattii was found in air, soil, water, and in association with numerous tree species. Importantly, there is solid evidence for human-mediated dispersal of the pathogen, and C. gattii has now been detected in the environment on the mainland of British Columbia and in the Pacific Northwest. Associated animal and human cases are now being reported and further spread of the pathogen may be inevitable.
Publisher: Oxford University Press (OUP)
Date: 07-10-2016
DOI: 10.1093/MMY/MYW093
Abstract: A wide array of PCR tests has been developed to aid the diagnosis of invasive aspergillosis (IA), providing technical ersity but limiting standardisation and acceptance. Methodological recommendations for testing blood s les using PCR exist, based on achieving optimal assay sensitivity to help exclude IA. Conversely, when testing more invasive s les (BAL, biopsy, CSF) emphasis is placed on confirming disease, so analytical specificity is paramount. This multicenter study examined the analytical specificity of PCR methods for detecting IA by blind testing a panel of DNA extracted from a various fungal species to explore the range of Aspergillus species that could be detected, but also potential cross reactivity with other fungal species. Positivity rates were calculated and regression analysis was performed to determine any associations between technical specifications and performance. The accuracy of Aspergillus genus specific assays was 71.8%, significantly greater (P < .0001) than assays specific for in idual Aspergillus species (47.2%). For genus specific assays the most often missed species were A. lentulus (25.0%), A. versicolor (24.1%), A. terreus (16.1%), A. flavus (15.2%), A. niger (13.4%), and A. fumigatus (6.2%). There was a significant positive association between accuracy and using an Aspergillus genus PCR assay targeting the rRNA genes (P = .0011). Conversely, there was a significant association between rRNA PCR targets and false positivity (P = .0032). To conclude current Aspergillus PCR assays are better suited for detecting A. fumigatus, with inferior detection of most other Aspergillus species. The use of an Aspergillus genus specific PCR assay targeting the rRNA genes is preferential.
Publisher: Oxford University Press (OUP)
Date: 2004
Publisher: American Society for Microbiology
Date: 11-2012
DOI: 10.1128/AAC.01115-12
Abstract: Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs for C. neoformans (including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans were evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included ≥95% of the modeled WT population, were as follows: fluconazole, 8 μg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII), 16 μg/ml ( C. neoformans nontyped, VNIII, and VGIV), and 32 μg/ml (VGII) itraconazole, 0.25 μg/ml (VNI), 0.5 μg/ml ( C. neoformans and C. gattii nontyped and VGI to VGIII), and 1 μg/ml (VGIV) posaconazole, 0.25 μg/ml ( C. neoformans nontyped and VNI) and 0.5 μg/ml ( C. gattii nontyped and VGI) and voriconazole, 0.12 μg/ml (VNIV), 0.25 μg/ml ( C. neoformans and C. gattii nontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 μg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.CIMID.2015.08.002
Abstract: Azole resistance is an emerging cause of treatment failure in humans with aspergillosis. The aim of this study was to determine if azole resistance is emerging in Aspergillus fumigatus isolates from canine and feline sino-nasal aspergillosis cases. Susceptibilities of isolates collected between 1988 and 2014 from 46 dogs and 4 cats to itraconazole, posaconazole, voriconazole, fluconazole and ketoconazole were assessed using Sensititre YeastOne microdilution trays and to enilconazole and clotrimazole, following the CLSI M38-A2 standard. For the majority of isolates MICs were high for ketoconazole, low for enilconazole and clotrimazole, and less than established epidemiological cut-off values for itraconazole, posaconazole and voriconazole. One canine isolate from 1992 had multiazole resistance and on Cyp51A gene sequencing a mutation associated with azole resistance (F46Y) was detected. There is no evidence of emerging azole resistance among A. fumigatus isolates from dogs and cats and topical azole therapy should be effective against most isolates.
Publisher: American Society of Tropical Medicine and Hygiene
Date: 03-12-2014
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.BIOTECHADV.2013.10.015
Abstract: Microbial attachment onto biomedical devices and implants leads to biofilm formation and infection such biofilms can be bacterial, fungal, or mixed. In the past 15 years, there has been an increasing research effort into antimicrobial surfaces but the great majority of these publications present research on bacteria, with some reports also testing resistance to fungi. Very few studies have focused exclusively on antifungal surfaces. However, with increasing recognition of the importance of fungal infections to human health, particularly related to infections at biomaterials, it would seem that the interest in antifungal surfaces is disproportionately low. In studies of both bacteria and fungi, fungi tend to be the minor focus with hypothesized antibacterial mechanisms of action often generalized to also explain the antifungal effect. Yet bacteria and fungi represent two Distinct biological Domains and possess substantially different cellular physiology and structure. Thus it is questionable whether these generalizations are valid. Here we review the scientific literature focusing on surface coatings prepared with antifungal agents covalently attached to the biomaterial surface. We present a critical analysis of generalizations and their evidence. This review should be of interest to researchers of "antimicrobial" surfaces by addressing specific issues that are key to designing and understanding antifungal biomaterials surfaces and their putative mechanisms of action.
Publisher: Public Library of Science (PLoS)
Date: 09-08-2017
Publisher: American Society for Microbiology
Date: 02-2016
DOI: 10.1128/AAC.02456-15
Abstract: The CLSI epidemiological cutoff values (ECVs) of antifungal agents are available for various Candida spp., Aspergillus spp., and the Mucorales. However, those categorical endpoints have not been established for Fusarium spp., mostly due to the difficulties associated with collecting sufficient CLSI MICs for clinical isolates identified according to the currently recommended molecular DNA-PCR-based identification methodologies. CLSI MIC distributions were established for 53 Fusarium dimerum species complex (SC), 10 F. fujikuroi , 82 F. proliferatum , 20 F. incarnatum-F. equiseti SC, 226 F. oxysporum SC, 608 F. solani SC, and 151 F. verticillioides isolates originating in 17 laboratories (in Argentina, Australia, Brazil, Canada, Europe, Mexico, and the United States). According to the CLSI guidelines for ECV setting, ECVs encompassing ≥97.5% of pooled statistically modeled MIC distributions were as follows: for hotericin B, 4 μg/ml ( F. verticillioides ) and 8 μg/ml ( F. oxysporum SC and F. solani SC) for posaconazole, 2 μg/ml ( F. verticillioides ), 8 μg/ml ( F. oxysporum SC), and 32 μg/ml ( F. solani SC) for voriconazole, 4 μg/ml ( F. verticillioides ), 16 μg/ml ( F. oxysporum SC), and 32 μg/ml ( F. solani SC) and for itraconazole, 32 μg/ml ( F. oxysporum SC and F. solani SC). Insufficient data precluded ECV definition for the other species. Although these ECVs could aid in detecting non-wild-type isolates with reduced susceptibility to the agents evaluated, the relationship between molecular mechanisms of resistance (gene mutations) and MICs still needs to be investigated for Fusarium spp.
Publisher: Wiley
Date: 11-2015
DOI: 10.1111/AJD.12223
Publisher: MDPI AG
Date: 31-03-2019
DOI: 10.3390/ANTIBIOTICS8020034
Abstract: Plant metabolites that have shown activity against bacteria and/or environmental fungi represent valuable leads for the identification and development of novel drugs against clinically important human pathogenic fungi. Plants from the genus Eremophila were highly valued in traditional Australian Aboriginal medicinal practices, and E. alternifolia was the most prized among them. As antibacterial activity of extracts from E. alternifolia has been documented, this study addresses the question whether there is also activity against infectious fungal human pathogens. Compounds from leaf-extracts were purified and identified by 1- and 2-D NMR. These were then tested by disk diffusion and broth microdilution assays against ten clinically and environmentally relevant yeast and mould species. The most potent activity was observed with the diterpene compound, 8,19-dihydroxyserrulat-14-ene against Cryptococcus gattii and Cryptococcus neoformans, with minimum inhibition concentrations (MIC) comparable to those of Amphotericin B. This compound also exhibited activity against six Candida species. Combined with previous studies showing an antibacterial effect, this finding could explain a broad antimicrobial effect from Eremophila extracts in their traditional medicinal usage. The discovery of potent antifungal compounds from Eremophila extracts is a promising development in the search for desperately needed antifungal compounds particularly for Cryptococcus infections.
Publisher: Elsevier BV
Date: 12-2018
Publisher: American Society for Microbiology
Date: 05-2009
DOI: 10.1128/JCM.00124-09
Abstract: Seven international laboratories tested the recently proposed single-locus typing strategy for Aspergillus fumigatus subtyping for interlaboratory reproducibility. Comparative sequence analyses of portions of the locus AFUA_3G08990, encoding a putative cell surface protein (denoted CSP), was performed with a panel of Aspergillus isolates. Each laboratory followed very different protocols for extraction of DNA, PCR, and sequencing. Results revealed that the CSP typing method was a reproducible and portable strain typing method.
Publisher: Informa UK Limited
Date: 05-2015
DOI: 10.2147/IDR.S57686
Publisher: Elsevier BV
Date: 2013
Publisher: Wiley
Date: 02-12-2020
DOI: 10.1111/TID.13516
Abstract: Microsporum canis is a dermatophyte known to cause superficial skin infections. In immunocompromised patients, it can lead to invasive dermatophytosis. We present a case of biopsy‐proven left knee mycetoma caused by M canis in a renal transplant patient. Identification of M canis was achieved via sequencing of the internal transcribed spacer regions. Treatment involved surgical debridement, oral posaconazole, and reduction in immunosuppression. In addition, we provide a review of current literature on invasive M canis infections.
Publisher: Elsevier BV
Date: 06-2019
Publisher: American Society for Microbiology
Date: 03-2019
DOI: 10.1128/AAC.02281-18
Abstract: Aspergillus fumigatus infections are associated with high mortality rates and high treatment costs. Limited available antifungals and increasing antifungal resistance highlight an urgent need for new antifungals.
Publisher: Cambridge University Press (CUP)
Date: 12-2009
DOI: 10.1086/648452
Abstract: Suspected nosocomial Aspergillus fumigatus infections in an Australian hematology unit were investigated by molecular typing of clinical and environmental isolates using polymerase chain reaction fingerprinting, CSP typing, and multilocus microsatellite typing. Only multilocus microsatellite typing revealed that all isolates were genetically distinct. The selection of an appropriate typing method is essential for effective outbreak investigations.
Publisher: Oxford University Press (OUP)
Date: 2023
DOI: 10.1093/OFID/OFAC559
Abstract: Fungal species have undergone and continue to undergo significant nomenclatural change, primarily due to the abandonment of dual species nomenclature in 2013 and the widespread application of molecular technologies in taxonomy allowing correction of past classification errors. These have effected numerous name changes concerning medically important species, but by far the group causing most concern are the Candida yeasts. Among common species, Candida krusei, Candida glabrata, Candida guilliermondii, Candida lusitaniae, and Candida rugosa have been changed to Pichia kudriavzevii, Nakaseomyces glabrata, Meyerozyma guilliermondii, Clavispora lusitaniae, and Diutina rugosa, respectively. There are currently no guidelines for microbiology laboratories on implementing changes, and there is ongoing concern that clinicians will dismiss or misinterpret laboratory reports using unfamiliar species names. Here, we have outlined the rationale for name changes across the major groups of clinically important fungi and have provided practical recommendations for managing change.
Publisher: Elsevier BV
Date: 12-2018
Publisher: Elsevier BV
Date: 06-2020
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.TVJL.2014.01.009
Abstract: On the basis of phenotypic identification methods, Aspergillus fumigatus is reported as the most commonly identified aetiological agent of canine sino-nasal aspergillosis (SNA). However, definitive identification of Aspergillus spp. using phenotypic features alone is unreliable. The aim of this study was to determine the molecular identities of fungal species causing SNA in dogs. Genomic DNA was extracted from 91 fungal isolates from 90 dogs diagnosed with SNA in Australia, the USA and Belgium, and the ITS1-5.8S-ITS2 ribosomal DNA and partial β-tubulin regions were sequenced. Eighty-eight of 91 (96.7%) isolates were identified as A. fumigatus and 3/91 (3.3%) belonged to Aspergillus section Nigri spp. (Aspergillus tubingensis: 2/91 Aspergillus uvarum: 1/91). These findings confirm that A. fumigatus is the most common aetiological agent of canine SNA. This is the first report to document a pathogenic role for A. tubingensis and A. uvarum in dogs.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 10-2016
Publisher: American Society for Microbiology
Date: 10-2005
DOI: 10.1128/EC.4.10.1629-1638.2005
Abstract: Cryptococcus gattii has recently emerged as a pathogen of humans and animals in the temperate climate of Vancouver Island, British Columbia (B.C.). The majority (∼95%) of the isolates from the island belong to the VGII molecular type, and the remainder belong to the VGI molecular type. The goals of this study were to compare patterns of molecular variation among C. gattii isolates from B.C. with those from different areas of the world and to investigate the population structure using a comparative gene genealogy approach. Our results indicate that the C. gattii population in B.C. comprises at least two ergent lineages, corresponding to previously identified VGI and VGII molecular types. The genealogical analysis of strains suggested a predominantly clonal population structure among B.C. isolates, while there was evidence for sexual recombination between different molecular types on a global scale. We found no geographic pattern of strain relationships, and nucleotide sequence comparisons revealed that genotypes among isolates from B.C. were also present among isolates from other areas of the world, indicating extensive strain dispersal. The nucleotide sequence ersity among isolates from B.C. was similar to that among isolates from other areas of the world.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 08-2009
Publisher: Wiley
Date: 05-05-2014
DOI: 10.1111/TID.12223
Abstract: Prototheca species are achlorophyllus algae. Prototheca wickerhamii and Prototheca zopfii cause human disease. In immunocompetent in iduals, they cause soft tissue infections and olecranon bursitis, but in transplant recipients, these organisms can cause disseminated disease. We report a fatal case of disseminated P. zopfii infection in an hematopoietic stem cell transplant (HSCT) recipient with bloodstream infection and involvement of multiple soft tissue sites. We review all previous cases of protothecosis in HSCT reported in the literature. Protothecosis is uncommon after HSCT, but has a disseminated presentation that is frequently fatal. It is commonly misidentified as a yeast. Tumor necrosis factor-alpha inhibitors and contamination of central venous catheters may contribute to development of protothecosis. Optimal treatment approaches are yet to be defined. New agents such as miltefosine may be possible future therapies.
Publisher: Oxford University Press (OUP)
Date: 08-2022
DOI: 10.1093/MMY/MYAC057
Abstract: Candida auris has significant implications for infection control due to its multidrug resistance and spread in healthcare settings. Current culture-based screening methods are laborious and risk muco-cutaneous colonisation of laboratory staff. We describe the adaptation of a published real-time PCR for the identification of C. auris in skin swabs for high-throughput infection control screening. Two published primer and probe sets were analysed utilising serial 10-fold dilutions of 15 C. auris strains to assess the PCR limit of detection. One primer and probe set was compatible with our laboratory workflow and was selected for further development yielding a limit of detection of 1 colony forming unit per reaction. Non-C. auris isolates as well as routine skin swabs (n = 100) were tested by culture and PCR to assess specificity, where no cross-reactivity was detected. Skin swabs from a proven C. auris case (n = 6) were all both culture positive and PCR positive, while surveillance swabs from close contacts (n = 46) were all both culture negative and PCR negative. Finally, the use of a lysis buffer comprising 4 m guanidinium thiocyanate rendered swab-equivalent quantities of C. auris non-viable, providing assurance of the safety benefit of PCR over culture. The development of a PCR assay for high-throughput infection control screening is a promising method for rapid detection of C. auris with utility in an outbreak setting. Candida auris, a difficult to treat yeast-like fungus, has spread through healthcare facilities globally, posing a serious threat to the health of patients. We evaluated a PCR-based method suitable for screening large numbers of patient s les to rapidly and accurately detect C. auris.
Publisher: American Society for Microbiology
Date: 10-2017
DOI: 10.1128/AAC.01057-17
Abstract: Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrix schenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of hotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto , 486 S. brasiliensis , 75 S. globosa , and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis , respectively: hotericin B, 4 and 4 μg/ml itraconazole, 2 and 2 μg/ml posaconazole, 2 and 2 μg/ml and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii , as well as ECVs for S. globosa and S. mexicana . These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.
Publisher: Oxford University Press (OUP)
Date: 15-06-2019
DOI: 10.1093/JAC/DKZ231
Abstract: To generate antifungal susceptibility patterns for Trichomonascus ciferrii (Candida ciferrii), Candida inconspicua (Torulopsis inconspicua) and Diutina rugosa species complex (Candida rugosa species complex), and to provide key parameters such as MIC50, MIC90 and tentative epidemiological cut-off values (TECOFFs). Our strain set included isolates of clinical origin: C. inconspicua (n = 168), D. rugosa species complex (n = 90) [Candida pararugosa (n = 60), D. rugosa (n = 26) and Candida mesorugosa (n = 4)], Pichia norvegensis (Candida norvegensis) (n = 15) and T. ciferrii (n = 8). Identification was performed by MALDI-TOF MS or internal transcribed spacer sequencing. Antifungal susceptibility patterns were generated for azoles, echinocandins and hotericin B using commercial Etest and the EUCAST broth microdilution method v7.3.1. Essential agreement (EA) was calculated for Etest and EUCAST. C. inconspicua, C. pararugosa and P. norvegensis showed elevated azole MICs (MIC50 ≥0.06 mg/L), and D. rugosa and C. pararugosa elevated echinocandin MICs (MIC50 ≥0.06 mg/L). EA between methods was generally low ( %) EA averaged 77.45%. TECOFFs were suggested for C. inconspicua and D. rugosa species complex. Rare yeast species tested shared high fluconazole MICs. D. rugosa species complex displayed high echinocandin MICs, while C. inconspicua and P. norvegensis were found to have high azole MICs. Overall, the agreement between EUCAST and Etest was poor and therefore MIC values generated with Etest cannot be directly compared with EUCAST results.
Publisher: CSIRO Publishing
Date: 08-04-2022
DOI: 10.1071/MA22005
Abstract: Dermatophyte fungi are a common cause of skin, nail and hair infections globally, ranging from mild to cosmetically disfiguring, or even invasive infections in rare cases. Specimens requiring fungal microscopy and culture for suspected dermatophyte infection make up a significant portion of the workload in diagnostic microbiology laboratories. Whilst still considered the gold standard, a dermatophyte culture-based method is labour intensive, has poor sensitivity, slow result turnaround time and requires significant expertise for identification of the fungi. Molecular diagnostics, especially real-time PCR, have the potential to improve diagnostic sensitivity, reduce labour requirements and decrease result turnaround times. Despite these advantages, a PCR-based approach may present some difficulties and disadvantages, most notably its diagnostic range and incompatibility with oral therapy prescribing requirements under the Pharmaceutical Benefits Scheme. Here we review current best practices and future prospects for laboratory diagnosis of dermatophyte infections, including the role of microscopy, culture and direct PCR.
Publisher: Oxford University Press (OUP)
Date: 30-11-2019
DOI: 10.1093/MMY/MYY126
Abstract: Whole genome sequencing (WGS) was used to demonstrate the wide genetic variability within Sporothrix schenckii sensu lato and establish that there are two main species of Sporothrix within Australian clinical isolates—S. schenckii sensu stricto and Sporothrix globosa. We also demonstrated southwest Western Australia contained genetically similar S. schenckii ss strains that are distinct from strains isolated in the eastern and northern states of Australia. Some genetic clustering by region was also noted for northern NSW, Queensland, and Northern Territory. Phylogenetic analysis of WGS data provided greater phylogenetic resolution compared to analysis of the calmodulin gene alone.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Oxford University Press (OUP)
Date: 2004
DOI: 10.1080/13693780310001644743
Abstract: A high bio ersity of Cryptococcus neoformans isolates is known to exist in some Brazilian urban areas, raising the possibility that patients may encounter multiple inoculum sources in their daily life. C. neoformans isolates from two groups of AIDS patients with cryptococcosis from Rio de Janeiro were studied by polymerase chain reaction (PCR) fingerprinting and randomly lified polymorphic DNA (RAPD) analysis. The first group contained 60 serial isolates obtained from 19 patients over periods ranging from 18 to 461 days the intent was to determine whether the original strain persisted or whether reinfection with a new strain occurred. The second group was made up of 22 isolates from 11 patients, and consisted of a pair of isolates collected from blood and cerebrospinal fluid from each patient either before or shortly after treatment was initiated. The aim was to determine if the patient was infected by different strains simultaneously. All isolates were subtyped by PCR fingerprinting, using minisatellite (M13), and microsatellite [(GACA)4 and (GTG)5] specific primers, and RAPD analysis employing the combined primers 5SOR and CN1. The majority of isolates were C. neoformans var. grubii, specifically, molecular types VNI or VNII, but numerous distinguishable subtypes were found. Only three isolates were C. n. var. gattii (molecular types VGI or VGII). Except in two cases, all isolates obtained from the same patient showed identical PCR profiles independent of time of isolation or body site. Almost all patients, however, carried unique genotypes not found in any other patient. Our results confirm that persistent cryptococcal infection is caused by relapse rather than reinfection, but they also show that in exceptional cases, patients may be infected with more than one C. neoformans strain.
Publisher: American Society for Microbiology
Date: 18-02-2021
DOI: 10.1128/JCM.02730-20
Publisher: Elsevier BV
Date: 03-2015
Publisher: American Society for Microbiology
Date: 04-2018
DOI: 10.1128/AAC.01916-17
Abstract: Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and nonmutant strains (strains harboring or not harboring mutations, respectively). Posaconazole MIC distributions for the Aspergillus fumigatus species complex were collected from 26 laboratories (in Australia, Canada, Europe, India, South and North America, and Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. The sensitivity of three ECV analytical techniques (the ECOFFinder, normalized resistance interpretation [NRI], derivatization methods) to the inclusion of MICs for mutants was examined for three susceptibility testing methods (the CLSI, EUCAST, and Etest methods). The totals of posaconazole MICs for nonmutant isolates (isolates with no known cyp51A mutations) and mutant A. fumigatus isolates were as follows: by the CLSI method, 2,223 and 274, respectively by the EUCAST method, 556 and 52, respectively and by Etest, 1,365 and 29, respectively. MICs for 381 isolates with unknown mutational status were also evaluated with the Sensititre YeastOne system (SYO). We observed an overlap in posaconazole MICs among nonmutants and cyp51A mutants. At the commonly chosen percentage of the modeled wild-type population (97.5%), almost all ECVs remained the same when the MICs for nonmutant and mutant distributions were merged: ECOFFinder ECVs, 0.5 μg/ml for the CLSI method and 0.25 μg/ml for the EUCAST method and Etest NRI ECVs, 0.5 μg/ml for all three methods. However, the ECOFFinder ECV for 95% of the nonmutant population by the CLSI method was 0.25 μg/ml. The tentative ECOFFinder ECV with SYO was 0.06 μg/ml (data from 3/8 laboratories). Derivatization ECVs with or without mutant inclusion were either 0.25 μg/ml (CLSI, EUCAST, Etest) or 0.06 μg/ml (SYO). It appears that ECV analytical techniques may not be vulnerable to overlap between presumptive wild-type isolates and cyp51A mutants when up to 11.6% of the estimated wild-type population includes mutants.
Publisher: Oxford University Press (OUP)
Date: 13-02-2017
DOI: 10.1093/JAC/DKX047
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 06-2015
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.ECOENV.2016.05.019
Abstract: The recent inclusion of yeasts in environmental monitoring recognizes their ecological significance and sensitivity to toxicants. Here we present a robust and simple two-step toxicity assay and demonstrate the sensitivity of an ubiquitous groundwater yeast, Rhodotorula minuta, to a range of metals and metalloids. The test species was sensitive to copper with a 24h EC50 of 35µg Cu/L, followed in order of decreasing sensitivity by zinc, chromium (VI) and arsenic (EC50 4.40mg As (III)/L). The strain demonstrated an unexpected tolerance to chromium (VI), having an EC50 value (3.45mg Cr (VI)/L) similar to that of arsenic. The inclusion of a unicellular, microbial test-species into the suite of existing multicellular test species for toxicity evaluation is a key step towards strengthening the assessment of risk for groundwater ecosystems.
Publisher: American Society for Microbiology
Date: 03-2007
DOI: 10.1128/AEM.01330-06
Abstract: Cryptococcus gattii has recently emerged as a primary pathogen of humans and wild and domesticated animals in British Columbia, particularly on Vancouver Island. C. gattii infections are typically infections of the pulmonary and/or the central nervous system, and the incidence of infection in British Columbia is currently the highest reported globally. Prior to this emergence, the environmental distribution of and the extent of colonization by C. gattii in British Columbia were unknown. We characterized the environmental sources and potential determinants of colonization in British Columbia. C. gattii was isolated from tree surfaces, soil, air, freshwater, and seawater, and no seasonal prevalence was observed. The C. gattii concentrations in air s les were significantly higher during the warm, dry summer months, although potentially infectious propagules ( .3 μm in diameter) were present throughout the year. Positive s les were obtained from many different areas of British Columbia, and some locations were colonization “hot spots.” C. gattii was generally isolated from acidic soil, and geographic differences in soil pH may influence the extent of colonization. C. gattii soil colonization also was associated with low moisture and low organic carbon contents. Most of the C. gattii isolates recovered belonged to the VGIIa genetic subtype however, sympatric colonization by the VGIIb strain was observed at most locations. At one s ling site, VGIIa, VGIIb, VGI, and the Cryptococcus neoformans serotype AD hybrid all were coisolated. Our findings indicate extensive colonization by C. gattii within British Columbia and highlight an expansion of the ecological niche of this pathogen.
Publisher: Oxford University Press (OUP)
Date: 2003
Abstract: Cryptococcus neoformans var. gattii has regularly been the cause of serious human disease. However, the environmental sources of these infections often remain unclear. During an environmental s ling study, two different strains of C. neoformans var. gattii were isolated from fresh insect frass (order Lepidoptera family Oecophoridae) in a shallow cavity in the bark of a living Eucalyptus tereticornis tree, one molecular type VGI and the other VGII. This is the first published report of the isolation of two different molecular types of C. neoformans var. gattii from a single source, and the third of isolation of molecular type VGII from an environmental source. The potential association with insect frass is consistent with categorising C. neoformans var. gattii within the Tremellales, containing mycoparasitic fungi.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2019
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 02-2011
Publisher: American Society for Microbiology
Date: 11-2019
DOI: 10.1128/AAC.00632-19
Abstract: The past decade has seen an increase in aspergillosis in humans and animals due to Aspergillus viridinutans species complex members. Azole resistance is common to these infections, carrying a poor prognosis. cyp51A gene mutations are the main cause of acquired azole resistance in Aspergillus fumigatus . This study aimed to determine if the azole-resistant phenotype in A. viridinutans complex members is associated with cyp51A mutations or extrolite profiles.
Publisher: American Society of Tropical Medicine and Hygiene
Date: 04-2015
Publisher: Elsevier BV
Date: 03-2019
Publisher: Public Library of Science (PLoS)
Date: 14-06-2013
Publisher: American Society for Microbiology
Date: 23-02-2022
DOI: 10.1128/SPECTRUM.02377-21
Abstract: Recent changes in fungal species names have been contentious, eliciting heated debate on social media. Despite available recommendations on adapting to the changes, concerns include clinicians dismissing pathogens as contaminants with patient harm as a result, and disruption of the literature.
Publisher: American Society for Microbiology
Date: 09-2007
DOI: 10.1128/JCM.00593-07
Abstract: We report a case of cryptococcosis due to C. gattii which appears to have been acquired in the Puget Sound region, Washington State. Genotyping confirmed identity to the predominant Vancouver Island genotype. This is the first documented case of human disease by the major Vancouver Island emergence strain acquired within the United States.
Publisher: Frontiers Media SA
Date: 27-09-2019
Publisher: CSIRO Publishing
Date: 2015
DOI: 10.1071/MA15022
Publisher: Oxford University Press (OUP)
Date: 21-07-2023
DOI: 10.1093/OFID/OFAD394
Publisher: Elsevier BV
Date: 04-2018
Publisher: ASM Press
Date: 09-04-2011
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: Elsevier BV
Date: 04-2015
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: Springer Science and Business Media LLC
Date: 30-09-2012
DOI: 10.1007/S11046-011-9475-X
Abstract: It has been over a decade since Cryptococcus gattii was first recognized as the causative organism of an outbreak of cryptococcosis on Vancouver Island, British Columbia. A number of novel observations have been associated with the study of this emergent pathogen. A novel genotype of C. gattii, VGIIa was described as the major genotype associated with clinical disease. Minor genotypes, VGIIb and VGI, are also responsible for disease in British Columbians, in both human and animal populations. The clinical major genotype VGIIa and minor genotype VGIIb are identical to C. gattii isolated from the environment of Vancouver Island. There is more heterogeneity in VGI, and a clear association with the environment is not apparent. Between 1999 and 2010, there have been 281 cases of C. gattii cryptococcosis. Risk factors for infection are reported to be age greater than 50 years, history of smoking, corticosteroid use, HIV infection, and history of cancer or chronic lung disease. The major C. gattii genotype VGIIa is as virulent in mice as the model Cryptococcus, H99 C. neoformans, although the outbreak strain produces a less protective inflammatory response in C57BL/6 mice. The minor genotype VGIIb is significantly less virulent in mouse models. Cryptococcus gattii is found associated with native trees and soil on Vancouver Island. Transiently positive isolations have been made from air and water. An ecological niche for this organism is associated within a limited biogeoclimatic zone characterized by daily average winter temperatures above freezing.
Publisher: American Society for Microbiology
Date: 03-2015
DOI: 10.1128/AAC.04435-14
Abstract: Clinical breakpoints (CBPs) have not been established for the Mucorales and any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for hotericin B, posaconazole, and itraconazole and four Mucorales species. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces variabilis , 32 Cunninghamella bertholletiae , 136 Lichtheimia corymbifera , 10 Mucor indicus , 123 M. circinelloides , 19 M. ramosissimus , 349 Rhizopus arrhizus , 146 R. microsporus , 33 Rhizomucor pusillus , and 36 Syncephalastrum racemosum isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: hotericin B ECVs for L. corymbifera were 1 and 2 μg/ml, those for M. circinelloides were 1 and 2 μg/ml, those for R. arrhizus were 2 and 4 μg/ml, and those for R. microsporus were 2 and 2 μg/ml, respectively posaconazole ECVs for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2, respectively both itraconazole ECVs for R. arrhizus were 2 μg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated.
Publisher: Springer Science and Business Media LLC
Date: 14-10-2020
DOI: 10.1186/S12879-020-05459-9
Abstract: Saksenaea species (spp.) are uncommon causes of mucormycosis but are emerging pathogens mostly associated with trauma and soil contamination often in immunocompetent hosts. Due to lack of sporulation in the laboratory, diagnosis and susceptibility testing is difficult so optimal treatment regimens are unknown. A 67 year-old man from the Northern Territory in Australia, with a history of eosinophilic granulomatosis with polyangiitis, developed disseminated Saksenaea infection after initially presenting with symptoms consistent with bacterial pyelonephritis. Despite a delay in diagnosis with aggressive surgical management and dual therapy with hotericin B and posaconazole, he survived. We describe an unusual case of disseminated infection with a favourable outcome to date.
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: 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: American Society for Microbiology
Date: 03-2011
Abstract: Cryptococcus gattii recently emerged as the causative agent of cryptococcosis in healthy in iduals in western North America, despite previous characterization of the fungus as a pathogen in tropical or subtropical regions. As a foundation to study the genetics of virulence in this pathogen, we sequenced the genomes of a strain (WM276) representing the predominant global molecular type (VGI) and a clinical strain (R265) of the major genotype (VGIIa) causing disease in North America. We compared these C. gattii genomes with each other and with the genomes of representative strains of the two varieties of Cryptococcus neoformans that generally cause disease in immunocompromised people. Our comparisons included chromosome alignments, analysis of gene content and gene family evolution, and comparative genome hybridization (CGH). These studies revealed that the genomes of the two representative C. gattii strains (genotypes VGI and VGIIa) are colinear for the majority of chromosomes, with some minor rearrangements. However, multiortholog phylogenetic analysis and an evaluation of gene/sequence conservation support the existence of speciation within the C. gattii complex. More extensive chromosome rearrangements were observed upon comparison of the C. gattii and the C. neoformans genomes. Finally, CGH revealed considerable variation in clinical and environmental isolates as well as changes in chromosome copy numbers in C. gattii isolates displaying fluconazole heteroresistance. IMPORTANCE Isolates of Cryptococcus gattii are currently causing an outbreak of cryptococcosis in western North America, and most of the cases occurred in the absence of coinfection with HIV. This pattern is therefore in stark contrast to the current global burden of one million annual cases of cryptococcosis, caused by the related species Cryptococcus neoformans , in the HIV/AIDS population. The genome sequences of two outbreak-associated major genotypes of C. gattii reported here provide insights into genome variation within and between cryptococcal species. These sequences also provide a resource to further evaluate the epidemiology of cryptococcal disease and to evaluate the role of pathogen genes in the differential interactions of C. gattii and C. neoformans with immunocompromised and immunocompetent hosts.
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.MIMET.2009.06.003
Abstract: A recently developed CSP typing scheme and proposed nomenclature was applied to a collection of 164 clinical and environmental Aspergillus fumigatus isolates from Melbourne, Australia. Fifteen CSP variants were observed overall, including three that were not reported in the original nomenclature that described 19 CSP variants, raising the possibility of phylogeographic differences between the Australian and the previously studied European and North American A. fumigatus populations. However, those CSP variants that were common between this and the previous studies appeared to have a broadly similar prevalence. The presence of an additional CCT codon in the 3' flanking region of some CSP variants was also observed in homologous Neosartorya fischeri sequence, suggesting that the absence of this codon in other isolates is due to codon deletion, rather than its presence representing a duplication. We recommend a number of modifications to the proposed CSP type nomenclature to accommodate these new findings.
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: Oxford University Press
Date: 12-2017
DOI: 10.1093/MED/9780198755388.003.0014
Abstract: The dematiaceous fungal pathogens, classified by their darkly pigmented hyphae, cause infection in both immunosuppressed and immunocompetent in iduals. Infections may present as chromoblastomycosis, mycetoma, and a spectrum of phaeohyphomycoses varying in severity. The route of infection may be through traumatic inoculation, or inhalation with or without dissemination. A number of species are considered neurotropic and can cause cerebral abscesses in immunocompetent persons. Infections can occur worldwide, but are most common in the tropics, and some species appear to have specific geographic ranges. Diagnosis requires s ling at the site of infection direct microscopy using KOH (potassium hydroxide), haematoxylin and eosin, and/or Fontana-Masson stains and culturing. Accurate species identification is essential. Treatment includes antifungal therapy with or without surgery, and antifungal susceptibility testing is recommended for all cultures.
Publisher: CABI
Date: 04-07-2022
No related grants have been discovered for Sarah Kidd.