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1.
Clin Microbiol Rev ; 37(2): e0000423, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38551323

RESUMO

SUMMARYAlthough Scedosporium species and Lomentospora prolificans are uncommon causes of invasive fungal diseases (IFDs), these infections are associated with high mortality and are costly to treat with a limited armamentarium of antifungal drugs. In light of recent advances, including in the area of new antifungals, the present review provides a timely and updated overview of these IFDs, with a focus on the taxonomy, clinical epidemiology, pathogenesis and host immune response, disease manifestations, diagnosis, antifungal susceptibility, and treatment. An expansion of hosts at risk for these difficult-to-treat infections has emerged over the last two decades given the increased use of, and broader population treated with, immunomodulatory and targeted molecular agents as well as wider adoption of antifungal prophylaxis. Clinical presentations differ not only between genera but also across the different Scedosporium species. L. prolificans is intrinsically resistant to most currently available antifungal agents, and the prognosis of immunocompromised patients with lomentosporiosis is poor. Development of, and improved access to, diagnostic modalities for early detection of these rare mold infections is paramount for timely targeted antifungal therapy and surgery if indicated. New antifungal agents (e.g., olorofim, fosmanogepix) with novel mechanisms of action and less cross-resistance to existing classes, availability of formulations for oral administration, and fewer drug-drug interactions are now in late-stage clinical trials, and soon, could extend options to treat scedosporiosis/lomentosporiosis. Much work remains to increase our understanding of these infections, especially in the pediatric setting. Knowledge gaps for future research are highlighted in the review.


Assuntos
Antifúngicos , Scedosporium , Humanos , Antifúngicos/uso terapêutico , Scedosporium/efeitos dos fármacos , Scedosporium/classificação , Farmacorresistência Fúngica , Micoses/tratamento farmacológico , Micoses/diagnóstico , Micoses/microbiologia , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Ascomicetos/classificação , Ascomicetos/efeitos dos fármacos
2.
Med Mycol ; 62(6)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935903

RESUMO

Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%-44%) in people living with HIV, with mortality rates ranging from 21% to 53%. Despite limited data, the prevalence of histoplasmosis seems stable, with lower estimates in Europe. Complications such as central nervous system disease, pulmonary issues, and lymphoedema due to granuloma or sclerosis are noted, though their burden remains uncertain. Antifungal susceptibility varies, particularly against fluconazole (MIC: ≥32 mg/l) and caspofungin (MICs: 4-32 mg/l), while resistance to amphotericin B (MIC: 0.125-0.16 mg/l), itraconazole (MICs: 0.004-0.125 mg/l), and voriconazole (MICs: 0.004-0.125 mg/l) remains low. This review identifies critical knowledge gaps, underlining the need for robust, globally representative surveillance systems to better understand and combat this fungal threat.


Assuntos
Antifúngicos , Farmacorresistência Fúngica , Histoplasma , Histoplasmose , Organização Mundial da Saúde , Humanos , Histoplasmose/epidemiologia , Histoplasmose/microbiologia , Histoplasmose/tratamento farmacológico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Histoplasma/efeitos dos fármacos , Histoplasma/isolamento & purificação , Prevalência , Hospedeiro Imunocomprometido
3.
Med Mycol ; 62(6)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935914

RESUMO

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required.


Assuntos
Antifúngicos , Fusarium , Testes de Sensibilidade Microbiana , Scedosporium , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fusarium/efeitos dos fármacos , Fusarium/isolamento & purificação , Scedosporium/efeitos dos fármacos , Scedosporium/isolamento & purificação , Scedosporium/classificação , Organização Mundial da Saúde , Micoses/epidemiologia , Micoses/microbiologia , Fusariose/microbiologia , Fusariose/epidemiologia , Ascomicetos/efeitos dos fármacos , Infecções Fúngicas Invasivas
4.
Intern Med J ; 52(3): 426-435, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32896984

RESUMO

BACKGROUND: Early, accurate diagnosis of invasive fungal disease (IFD) improves clinical outcomes. 1,3-beta-d-glucan (BDG) (Fungitell, Associates of Cape Cod, Inc., Falmouth, MA, USA) detection can improve IFD diagnosis but has been unavailable in Australia. AIMS: To assess performance of serum BDG for IFD diagnosis in a high-risk Australian haematology population. METHODS: We compared the diagnostic value of weekly screening of serum BDG with screening by Aspergillus polymerase chain reaction and Aspergillus galactomannan in 57 at-risk episodes for the diagnosis of IFD (proven, probable, possible IFD). RESULTS: IFD episodes were: proven (n = 4); probable (n = 4); possible (n = 18); and no IFD (n = 31). Using two consecutive BDG results of ≥80 pg/mL to call a result 'positive', the sensitivity, specificity, positive predictive value and negative predictive value was 37.5%, 64.5%, 23.1% and 80.7% respectively. For invasive aspergillosis, test performance increased to 50%, 90.3%, 57.1% and 87.5% respectively if any two of serum BDG/Aspergillus polymerase chain reaction/galactomannan yielded a 'positive' result. In proven/probable IFD, five of eight episodes returned a positive BDG result earlier (mean 6.6 days) than other diagnostic tests. False-negative BDG results occurred in three of eight episodes of proven/probable IFD, and false positive in 10 of 31 patients with no IFD. Erratic patterns of BDG values predicted false positive results (P = 0.03). Using serum BDG results, possible IFD were reassigned to either 'no' or 'probable' IFD in 44% cases. Empiric anti-fungal therapy use may have been optimised by BDG monitoring in 38.5% of courses. CONCLUSIONS: The BDG assay can add diagnostic speed and value but was hampered by low sensitivity and positive predictive value in Australian haematology patients.


Assuntos
Hematologia , Micoses , beta-Glucanas , Austrália/epidemiologia , Humanos , Sensibilidade e Especificidade , beta-Glucanas/análise
5.
Environ Microbiol ; 23(12): 7632-7642, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34232541

RESUMO

Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34 /L98H most frequent (34/38).


Assuntos
Aspergillus fumigatus , Azóis , Antifúngicos/farmacologia , Azóis/farmacologia , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Testes de Sensibilidade Microbiana , Vietnã
6.
Intern Med J ; 51 Suppl 7: 143-176, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34937136

RESUMO

Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID-19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological-based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non-culture methods employing fungal biomarkers in pre-emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first-line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological-based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations.


Assuntos
Aspergilose , COVID-19 , Adulto , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus fumigatus , Criança , Farmacorresistência Fúngica , Humanos , SARS-CoV-2 , Voriconazol/uso terapêutico
8.
Intern Med J ; 49(10): 1229-1243, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31424595

RESUMO

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 amphotericin 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, amphotericin 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.


Assuntos
Antifúngicos/uso terapêutico , Candida/isolamento & purificação , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Candidíase/prevenção & controle , Fatores Etários , Austrália , Candida/efeitos dos fármacos , Candida/genética , Candidíase/mortalidade , Infecção Hospitalar/prevenção & controle , DNA Fúngico/genética , Transmissão de Doença Infecciosa/prevenção & controle , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Humanos , Controle de Infecções/métodos , Testes de Sensibilidade Microbiana , Nova Zelândia , Sociedades Médicas
9.
J Antimicrob Chemother ; 73(9): 2347-2351, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29846581

RESUMO

Background: The prevalence of azole resistance in Aspergillus fumigatus is uncertain in Australia. Azole exposure may select for resistance. We investigated the frequency of azole resistance in a large number of clinical and environmental isolates. Methods: A. fumigatus isolates [148 human, 21 animal and 185 environmental strains from air (n = 6) and azole-exposed (n = 64) or azole-naive (n = 115) environments] were screened for azole resistance using the VIPcheck™ system. MICs were determined using the Sensititre™ YeastOne YO10 assay. Sequencing of the Aspergillus cyp51A gene and promoter region was performed for azole-resistant isolates, and cyp51A homology protein modelling undertaken. Results: Non-WT MICs/MICs at the epidemiological cut-off value of one or more azoles were observed for 3/148 (2%) human isolates but not amongst animal, or environmental, isolates. All three isolates grew on at least one azole-supplemented well based on VIPcheck™ screening. For isolates 9 and 32, the itraconazole and posaconazole MICs were 1 mg/L (voriconazole MICs 0.12 mg/L); isolate 129 had itraconazole, posaconazole and voriconazole MICs of >16, 1 and 8 mg/L, respectively. Soil isolates from azole-exposed and azole-naive environments had similar geometric mean MICs of itraconazole, posaconazole and voriconazole (P > 0.05). A G54R mutation was identified in the isolates exhibiting itraconazole and posaconazole resistance, and the TR34/L98H mutation in the pan-azole-resistant isolate. cyp51A modelling predicted that the G54R mutation would prevent binding of itraconazole and posaconazole to the haem complex. Conclusions: Azole resistance is uncommon in Australian clinical and environmental A. fumigatus isolates; further surveillance is indicated.


Assuntos
Antifúngicos/farmacologia , Aspergilose/microbiologia , Aspergillus fumigatus/efeitos dos fármacos , Azóis/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica , Microbiologia Ambiental , Proteínas Fúngicas/genética , Aspergilose/epidemiologia , Aspergillus fumigatus/enzimologia , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Austrália/epidemiologia , Monitoramento Epidemiológico , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Análise de Sequência de DNA
10.
Curr Opin Infect Dis ; 30(6): 565-572, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29095722

RESUMO

PURPOSE OF REVIEW: Bloodstream infections are a major cause of hospital and ICU admission with high morbidity and mortality; however, early and targeted antimicrobial therapy reduces mortality in high-risk patients. This article focuses on the diagnosis of bloodstream infections by PCR-based approaches at an early stage to enable prompt treatment and prevent organ dysfunction. RECENT FINDINGS: PCR systems offering highly multiplexed targeting of bacterial and/or fungal pathogens (in whole blood) offer the best opportunity for clinical impact, as informed decisions can be made within 4-8 h of the blood draw. Although more rapid, these systems are typically associated with lower sensitivity and specificity than postculture detection methods which rely on microbial growth. Additionally, unlike postculture methods, detection directly from blood is not prone to misleading results because of concurrent (or previous) therapy, which limit clinical relevance. SUMMARY: Rapid and accurate identification of the cause of sepsis is essential in improving patient outcomes. Early identification of these pathogens by nucleic acid detection assays directly from blood samples remains key to achieving this, particularly if taken at the time of presentation. Selection of the most suitable PCR system is typically influenced by local epidemiology and by the resources of the testing laboratory.


Assuntos
Tipagem Molecular , Reação em Cadeia da Polimerase , Sepse , Bactérias/genética , DNA Bacteriano/análise , DNA Bacteriano/genética , DNA Fúngico/análise , DNA Fúngico/genética , Fungos/genética , Humanos , Sepse/diagnóstico , Sepse/microbiologia
12.
J Clin Microbiol ; 54(8): 2182-6, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27252460

RESUMO

We developed an Australian database for the identification of Aspergillus, Scedosporium, and Fusarium species (n = 28) by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). In a challenge against 117 isolates, species identification significantly improved when the in-house-built database was combined with the Bruker Filamentous Fungi Library compared with that for the Bruker library alone (Aspergillus, 93% versus 69%; Fusarium, 84% versus 42%; and Scedosporium, 94% versus 18%, respectively).


Assuntos
Aspergillus/isolamento & purificação , Fusarium/isolamento & purificação , Técnicas Microbiológicas/métodos , Micoses/diagnóstico , Micoses/microbiologia , Scedosporium/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Aspergillus/química , Austrália , Fungos , Fusarium/química , Scedosporium/química
13.
Pathology ; 55(5): 669-672, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37316383

RESUMO

Performance of panfungal PCR-DNA sequencing assays for diagnosis of invasive fungal disease on formalin-fixed, paraffin-embedded tissue (FFPE) is influenced by many variables. Interpretation of a positive result can be challenging due to the need to differentiate colonisers and contaminants from clinically significant pathogens. We conducted a retrospective audit on FFPE tissue specimens that underwent panfungal PCR from January 2021 to August 2022. Panfungal PCR results from samples where fungal elements were visualised on histopathology were compared with results from samples where no fungal elements were visualised. The cost per clinically significant positive sample in each group was calculated. Of the 248 FFPE tissues sampled, 18.1% (45/248) had fungal forms seen on histopathology. Panfungal PCR was positive in 22/45 samples (48.9%), with 16 (35.6%) results deemed clinically significant. For the remaining 203 specimens, panfungal PCR was positive in 19 (9.4%) samples with only six (3.0%) clinically significant. The average cost per clinically significant result was AUD 258.13 in the histopathology positive group and AUD 3,105.22 in the histopathology negative group. Our data suggest panfungal PCR has limited clinical utility in FFPE tissue when no fungal elements are seen. Restricting the assay to only those samples that are positive on histopathological examination aids interpretation of PCR positive results and conserves laboratory resources.


Assuntos
Infecções Fúngicas Invasivas , Humanos , Estudos Retrospectivos , Inclusão em Parafina , Infecções Fúngicas Invasivas/diagnóstico , Reação em Cadeia da Polimerase/métodos , Fixação de Tecidos , Formaldeído
14.
J Fungi (Basel) ; 9(11)2023 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-37998865

RESUMO

Nosocomial clusters of fungal infections, whilst uncommon, cannot be predicted and are associated with significant morbidity and mortality. Here, we review reports of nosocomial outbreaks of invasive fungal disease to glean insight into their epidemiology, risks for infection, methods employed in outbreak detection including genomic testing to confirm the outbreak, and approaches to clinical and infection control management. Both yeasts and filamentous fungi cause outbreaks, with each having general and specific risks. The early detection and confirmation of the outbreak are essential for diagnosis, treatment of affected patients, and termination of the outbreak. Environmental sampling, including the air in mould outbreaks, for the pathogen may be indicated. The genetic analysis of epidemiologically linked isolates is strongly recommended through a sufficiently discriminatory approach such as whole genome sequencing or a method that is acceptably discriminatory for that pathogen. An analysis of both linked isolates and epidemiologically unrelated strains is required to enable genetic similarity comparisons. The management of the outbreak encompasses input from a multi-disciplinary team with epidemiological investigation and infection control measures, including screening for additional cases, patient cohorting, and strict hygiene and cleaning procedures. Automated methods for fungal infection surveillance would greatly aid earlier outbreak detection and should be a focus of research.

15.
J Fungi (Basel) ; 9(6)2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37367595

RESUMO

Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds. These pathogens are a WHO-assigned high-priority pathogen group, as mucormycosis incidence is increasing, and there is unacceptably high mortality with current antifungal therapies. Current diagnostic methods have inadequate sensitivity and specificity and may have issues with accessibility or turnaround time. Patients with diabetes mellitus and immune compromise are predisposed to infection with these environmental fungi, but COVID-19 has established itself as a new risk factor. Mucorales also cause healthcare-associated outbreaks, and clusters associated with natural disasters have also been identified. Robust epidemiological surveillance into burden of disease, at-risk populations, and emerging pathogens is required. Emerging serological and molecular techniques may offer a faster route to diagnosis, while newly developed antifungal agents show promise in preliminary studies. Equitable access to these emerging diagnostic techniques and antifungal therapies will be key in identifying and treating mucormycosis, as delayed initiation of therapy is associated with higher mortality.

16.
Transplant Direct ; 9(1): e1430, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36582672

RESUMO

Fungal infections are a recognized complication of immunosuppression in solid organ transplant recipients. Phaeohyphomycoses are fungal infections caused by a diverse group of dematiaceous fungi. Methods: We share the learning points from 2 Australian cases of phaeohyphomycosis secondary to Phaeacreomonium species (spp). A literature review was performed using Medline, Embase, and Google Scholar to identify this condition among kidney transplant recipients. Results: With the 2 cases reported in this article, a total of 17 cases were identified in the literature. Phaeacremonium spp is ubiquitous in humid and temperate flora, including Australia. Minor trauma is likely the source of inoculation in most cases and diagnosis is often delayed. Presently, no guidelines for management exist given the rarity of this condition. Most known cases have been treated with surgical debulking combined with long-course antifungal therapy. Conclusion: This paper describes 2 Australian cases of phaeohyphomycosis in kidney transplant recipients. A high index of suspicion, especially in the immunosuppressed, is essential for timely diagnosis in kidney transplant recipients. There are several diagnostic and therapeutic challenges that remain with this condition.

17.
Lancet Reg Health West Pac ; 40: 100888, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37701716

RESUMO

Background: New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice. Methods: The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017-December 2020). Descriptive analyses were used to report patients' demographics, predisposing factors, mycological characteristics, diagnosis and management. Accelerated failure-time model was employed to determine factor(s) associated with 90-day all-cause mortality (ACM). Findings: Of 382 IA episodes, 221 (in 221 patients) fulfilled inclusion criteria - 53 proven and 168 probable IA. Median patient age was 61 years (IQR 51-69). Patients with haematologic malignancies (HM) comprised 49.8% of cases. Fifteen patients (6.8%) had no pre-specified immunosuppression and eleven patients (5.0%) had no documented comorbidity. Only 30% of patients had neutropenia. Of 170 isolates identified, 40 (23.5%) were identified as non-Aspergillus fumigatus species complex. Azole-resistance was present in 3/46 (6.5%) of A. fumigatus sensu stricto isolates. Ninety-day ACM was 30.3%. HM (HR 1.90; 95% CI 1.04-3.46, p = 0.036) and ICU admission (HR 4.89; 95% CI 2.93-8.17, p < 0.001) but not neutropenia (HR 1.45; 95% CI 0.88-2.39, p = 0.135) were associated with mortality. Chronic kidney disease was also a significant predictor of death in the HM subgroup (HR 3.94; 95% CI 1.15-13.44, p = 0.028). Interpretation: IA is identified in high number of patients with mild/no immunosuppression in our study. The relatively high proportion of non-A. fumigatus species complex isolates and 6.5% azole-resistance rate amongst A. fumigatus sensu stricto necessitates accurate species identification and susceptibility testing for optimal patient outcomes. Funding: This work is unfunded. All authors' financial disclosures are listed in detail at the end of the manuscript.

18.
J Fungi (Basel) ; 8(5)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35628719

RESUMO

Cryptococcus neoformans and Cryptococcus gattii are the principle causative agents of cryptococcosis. Differences in epidemiological and clinical features, and also treatment, mean it is important for diagnostic laboratories to distinguish between the two species. Molecular methods are potentially more rapid than culture and cryptococcal antigen (CRAG) detection; however, commercial PCR-based assays that target Cryptococcus do not distinguish between species. Here, we developed a real-time PCR assay targeting the multicopy mitochondrial cytochrome b (cyt b) gene to detect C. neoformans and C. gattii in clinical specimens. Assay performance was compared with culture, histopathology, CRAG and panfungal PCR/DNA sequencing. The cyt b-directed assay accurately detected and identified all eight C. neoformans/gattii genotypes. High-resolution melt curve analysis unambiguously discriminated between the two species. Overall, assay sensitivity (96.4%) compared favorably with panfungal PCR (76.9%) and culture (14.5%); assay specificity was 100%. Of 25 fresh frozen paraffin embedded (FFPE) specimens, assay sensitivity was 96% (76% for panfungal PCR; 68% for histopathology). The Cryptococcus-specific PCR is a rapid (~4 h) sensitive method to diagnose (or exclude) cryptococcosis and differentiate between the two major species. It is suitable for use on diverse clinical specimens and may be the preferred molecular method for FFPE specimens where clinical suspicion of cryptococcosis is high.

19.
Microbiol Spectr ; 10(1): e0237721, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35138169

RESUMO

Fungal nomenclature changes have been a regular occurrence in recent years, eliciting heated debate on whether such changes will confuse clinicians and harm patients. We conducted surveys of Australasian laboratory staff and clinicians to assess attitudes, practices, and concerns regarding nomenclatural change. The majority of respondents to both surveys were aware of fungal nomenclatural changes (93.5% laboratories, 79.7% clinicians); 72.8% of laboratories had already implemented nomenclature changes, and 68.7% of clinicians recalled receiving at least one laboratory report utilizing updated fungal nomenclature. The vast majority of clinicians (94%) both within and outside of infection specialties supported laboratories reporting updated species names with inclusion of the previous species name. The importance of including the previous name on reports was demonstrated by 73.3% of clinicians viewing "Nakaseomyces glabrata (formerly Candida glabrata)" as clinically significant, versus only 38.2% viewing "Pichia kudriavzeveii" as significant in the absence of its former name. When asked about reporting practices, 73.9% of laboratories would report a Candida krusei isolate as "Pichia kudriavzeveii (formerly Candida krusei)," with the rest reporting as "Candida krusei" (21.7%) or "Pichia kudriavzeveii" (1.1%) without further explanation. Laboratory concerns included clinicians being confused by reports, commonly used identification platforms continuing to use superseded species names, education of staff, and delays in updating species codes in laboratory information systems. Adopting fungal name changes appears to be well supported by laboratories and clinicians in Australia and New Zealand, and can be achieved safely and unambiguously provided the former name is included on reports. IMPORTANCE 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. Such concerns are understandable, but are not supported by evidence and may represent a vocal minority. This survey of Australasian laboratories and clinicians assesses attitudes and practices relating to changes in fungal nomenclature and found that there is overwhelming support for adopting nomenclature changes.


Assuntos
Fungos/classificação , Pessoal de Laboratório/psicologia , Médicos/psicologia , Atitude , Atitude do Pessoal de Saúde , Austrália , Fungos/genética , Humanos , Terminologia como Assunto
20.
Pathology ; 54(7): 922-927, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35931494

RESUMO

This study aimed to validate the performance of the custom formulated Sensititre YeastOne One (SYO) microdilution plate which includes isavuconazole (AUSNMRC1) to perform susceptibility testing on clinically relevant yeast and mould species across three Australian reference laboratories. The minimum inhibitory concentration (MIC) results were compared with the IVD approved SYO YO10 microdilution plate and isavuconazole gradient strips. A total of 127 isolates were tested on both the YO10 and AUSNMRC1 plates. The overall essential agreement (EA) and categorical agreement (CA) for the eight common drugs was 99.9% and 98.8%, respectively. The EA was 96.9% for the isavuconazole MICs obtained using the AUSNMRC1 plate and gradient strip. The MIC results for all nine antifungals on the AUSNMRC1 panel were highly reproducible for all quality control and reference strains and the overall EA and CA for 45 clinical strains tested across all three participating laboratories were >93% and 94.1%, respectively. These findings demonstrate the SYO AUSNMRC1 plate provides a commercial means to determine isavuconazole MICs by broth microdilution testing.


Assuntos
Antifúngicos , Saccharomyces cerevisiae , Humanos , Antifúngicos/farmacologia , Micologia , Laboratórios , Austrália , Testes de Sensibilidade Microbiana
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