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mBio ; 11(2)2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345637


Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris IMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

J Chemother ; 31(3): 137-140, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30955472


Candidemia is a common invasive fungal infection with a high mortality rate. We performed a retrospective audit of candidemia at a tertiary centre in Western Australia, 2005-2014. There were 167 episodes of candidemia due to 173 isolates of Candida. Candida albicans (40.5%), Candida glabrata complex (30.6%), Candida parapsilosis complex (14.4%) were the most common species causing candidemia across the study. Of the tested isolates, 17.7% (11/62) were non-susceptible to fluconazole and 13.6% (9/66) non-susceptible to caspofungin. 22.8% (8/35) C. glabrata complex were fluconazole resistant and 17.1% (6/35) were non-susceptible to caspofungin. Candida glabrata complex was more common in the latter time period, but there were no susceptibility changes over time. In our setting, the prevalence of C. glabrata complex and antifungal non-susceptibility is high, and the prevalence of C. glabrata complex is increasing.

Antifúngicos/farmacologia , Candida parapsilosis/isolamento & purificação , Candidemia/epidemiologia , Candidemia/microbiologia , Farmacorresistência Fúngica , Austrália/epidemiologia , Candida parapsilosis/efeitos dos fármacos , Candidemia/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Estudos Retrospectivos
Emerg Infect Dis ; 25(1): 192-194, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561310


In Australia in 2015, Candida auris sternal osteomyelitis was diagnosed in a 65-year-old man with a history of intensive care treatment in Kenya in 2012 and without a history of cardiac surgery. The isolate was South Africa clade III. Clinicians should note that C. auris can cause low-grade disease years after colonization.

Antifúngicos/administração & dosagem , Candida/isolamento & purificação , Candidíase/diagnóstico por imagem , Osteomielite/diagnóstico por imagem , Triazóis/administração & dosagem , Idoso , Austrália , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/microbiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Doença Crônica , Evolução Fatal , Humanos , Quênia , Masculino , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Tomografia Computadorizada por Raios X , Viagem , Sequenciamento Completo do Genoma
Med Mycol ; 52(8): 819-25, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25288654


Cutaneous disease is the third most frequent manifestation of mucormycosis. The clinical manifestations of and subsequent mortality due to cutaneous mucormycosis are dependent on the mode of acquisition and the host immune status. Here, we describe the epidemiology, clinical presentation, microbiology, and outcomes of 16 cutaneous mucormycosis infections managed in an Australian tertiary hospital over a 15-year period. The proportion with localized (56%), deep (38%), and disseminated (6%) cutaneous disease as well as the overall mortality (25%) were consistent with findings reported in the published literature. Two novel forms of hospital-acquired infection were reported following a sacral pressure sore and insertion of a foreign body during a bone graft procedure. The majority of patients were immunocompetent (75%) and/or suffered trauma (56%) with associated environmental contamination. A novel finding was that motor vehicle accidents (MVAs) accounted for 78% of all trauma-related cases, suggesting MVAs should receive greater recognition as a potential precipitant of cutaneous mucormycosis. Aggressive decontamination and debridement of devitalized tissue following trauma is therefore likely to play an important role in the prevention of this rare but potentially devastating infection.

Acidentes de Trânsito , Dermatomicoses , Mucormicose , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Dermatomicoses/diagnóstico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/epidemiologia , Dermatomicoses/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/epidemiologia , Mucormicose/microbiologia , Estudos Retrospectivos , Adulto Jovem
Diagn Microbiol Infect Dis ; 54(4): 289-97, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16466900


We report a direct polymerase chain reaction/sequence (d-PCRS)-based method for the rapid identification of clinically significant fungi from 5 different types of commercial broth enrichment media inoculated with clinical specimens. Media including BacT/ALERT FA (BioMérieux, Marcy l'Etoile, France) (n = 87), BACTEC Plus Aerobic/F (Becton Dickinson, Microbiology Systems, Sparks, MD) (n = 16), BACTEC Peds Plus/F (Becton Dickinson) (n = 15), BACTEC Lytic/10 Anaerobic/F (Becton Dickinson) (n = 11) bottles, and BBL MGIT (Becton Dickinson) (n = 11) were inoculated with specimens from 138 patients. A universal DNA extraction method was used combining a novel pretreatment step to remove PCR inhibitors with a column-based DNA extraction kit. Target sequences in the noncoding internal transcribed spacer regions of the rRNA gene were amplified by PCR and sequenced using a rapid (24 h) automated capillary electrophoresis system. Using sequence alignment software, fungi were identified by sequence similarity with sequences derived from isolates identified by upper-level reference laboratories or isolates defined as ex-type strains. We identified Candida albicans (n = 14), Candida parapsilosis (n = 8), Candida glabrata (n = 7), Candida krusei (n = 2), Scedosporium prolificans (n = 4), and 1 each of Candida orthopsilosis, Candida dubliniensis, Candida kefyr, Candida tropicalis, Candida guilliermondii, Saccharomyces cerevisiae, Cryptococcus neoformans, Aspergillus fumigatus, Histoplasma capsulatum, and Malassezia pachydermatis by d-PCRS analysis. All d-PCRS identifications from positive broths were in agreement with the final species identification of the isolates grown from subculture. Earlier identification of fungi using d-PCRS may facilitate prompt and more appropriate antifungal therapy.

Meios de Cultura , DNA Fúngico/análise , Fungos Mitospóricos/isolamento & purificação , Micoses/diagnóstico , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA , Custos e Análise de Custo , DNA Intergênico/genética , Humanos , Fungos Mitospóricos/genética , Fungos Mitospóricos/crescimento & desenvolvimento , Reação em Cadeia da Polimerase/economia , Transcrição Genética