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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., 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.

Item does not contain fulltext BACKGROUND: Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. METHODS: To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012-2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). RESULTS: Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9-36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. CONCLUSIONS: C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

Background. Candida auris is a multidrug-resistant yeast that can cause invasive fungal infections. It was first described in Japan in 2009, and has since been reported in other parts of the world. We established an international collaboration to understand the epidemiology of this emerging pathogen. Methods. We evaluated a convenience sample of C. auris infections from India, Pakistan, South Africa, and Venezuela during 2012–2015. Antifungal susceptibility testing was conducted according to CLSI standards; breakpoints were defined using those from other Candida spp. Whole genome sequencing typing (WGST) was performed. Patient information was obtained using a standardized case report form. Results. Isolates from 54 patients were evaluated (Pakistan 19, India 19, South Africa 10, Venezuela 5, and 1 reference isolate from Japan). All were resistant to fluconazole, 54% to voriconazole, and 7% to echinocandins; resistance to amphotericin B (MIC ≥2) was found in 29% of 21 isolates tested. At least 24% of isolates were resistant to ≥2 antifungal classes. Isolates grouped into distinct South Asian, East Asian, African, and South American clades by WGST. Clades were separated by several thousand single nucleotide polymorphisms (SNPs), but within each clade, isolates were clonal (0–70 SNP differences). Among 38 patients with clinical information, median age was 54 years and 62% were male. Possible risk factors included central venous catheter (CVC) use (78%), surgery in the previous 90 days (50%), recent antifungal therapy (47%), and diabetes (42%). Median time from admission to C. auris culture was 17 days; 63% of patients had bloodstream infections, 16% had urinary tract infections, and 61% died. Conclusion. C. auris is an emerging healthcare-associated pathogen most commonly identified in patients with CVCs and recent surgery and antifungal therapy. It is associated with higher mortality than other Candida spp., and treatment options are limited because of the high prevalence of antifungal resistance. Puzzlingly, WGST analysis suggests emergence at least 4 distinct clades with high genomic similarity within geographical regions. Further exploration of risk factors for infection and transmission mechanisms is needed to inform control measures.

Item does not contain fulltext OBJECTIVES: Characterization of a hospital outbreak of Candida auris candidemia that involved 18 critically ill patients in Venezuela. METHOD: Bloodstream isolates of C. auris obtained from 18 patients admitted at a medical center in Maracaibo, between March, 2012 and July, 2013 were included. Species identification was confirmed by ITS rDNA sequencing. Isolates were subsequently typed by amplified fragment length polymorphism fingerprinting (AFLP). Susceptibility testing was performed according to CLSI. Clinical data were collected from all cases by using a standard clinical form. RESULTS: A total of 13 critically ill pediatric and 5 adult patients, with a median age of 26 days, were included. All were previously exposed to antibiotics and multiple invasive medical procedures. Clinical management included prompt catheter removal and antifungal therapy. Thirteen patients (72%) survived up to 30 days after onset of candidemia. AFLP fingerprinting of all C. auris isolates suggested a clonal outbreak. The isolates were considered resistant to azoles, but susceptible to anidulafungin and 50% of isolates exhibited amphotericin B MIC values of >1 mug/ml. CONCLUSIONS: The study demonstrated that C. auris is a multiresistant yeast pathogen that can be a source of health-care associated infections in tertiary care hospitals with a high potential for nosocomial horizontal transmission.

The aim of this study was to determine the in vitro susceptibility of amphotericin B, fluconazole and itraconazole, to several Candida spp recovered from blood cultures on hospitalized patients at the University Hospital of Maracaibo, Venezuela. The determination of the antifungal susceptibility was carried out according to the microdilution method in broth developed by The European Committee for Antimicrobial Susceptibility Testing (EUCAST). The profile of susceptibility of the 74 isolates showed that all the studied species were susceptible to amphotericin B, and 97.2% and 89.2% to fluconazole and itraconazole, respectively.

From March 1999 to March 2000, we conducted a prospective multicenter study of candidemia involving five tertiary care hospitals from four countries in Latin America. Yeast isolates were identified by classical methods and the antifungal susceptibility profile was determined according to the National Committee for Clinical Laboratory Standards microbroth assay method. During a 12 month-period we were able to collect a total of 103 bloodstream isolates of Candida spp. C. albicans was the most frequently isolated species accounting for 42% of all isolates. Non-albicans Candida species strains accounted for 58% of all episodes of candidemia and were mostly represented by C. tropicalis (24.2%) and C. parapsilosis (21.3%). It is noteworthy that we were able to identify two cases of C. lusitaniae from different institutions. In our casuistic, non-albicans Candida species isolates related to candidemic episodes were susceptible to fluconazole. Continuously surveillance programs are needed in order to identify possible changes in the species distribution and antifungal susceptibility patterns of yeasts that may occurs after increasing the use of azoles in Latin American hospitals.

One hundred clinical isolates of Cryptococcus neoformans from human immunodeficiency virus (HIV)-infected and non-HIV-infected patients from Brazil, Chile, and Venezuela were separated according to varieties and tested for antifungal susceptibility. A high susceptibility to antifungal agents was observed among all the isolates. The electrophoretic karyotyping of 51 strains revealed good discrimination among Cryptococcus neoformans var. neoformans strains.

Antígeno del polisacárido capsular (Ag PC) de Cryptococcus neoformans fue detectado por la técnica de aglutinación de latex (AL) en LCR y suero de pacientes con Sindrome de Inmunodeficiencia Adquirida (SIDA) y primer episodio de neurocriptococosis, usando como patrón el examen micológico (examen directo y cultivo) de LCR. Se obtuvo una sensibilidad del 100% de AL para detectar AgPC de C. neoformans, el cual por su rápidez permite tratamiento específico precoz. Títulos iniciales de AgPC de la levadura en esos pacientes pueden ser > 1.000.000, pareciendo que cuando esos títulos están presentes en suero, se relacionan con mortalidad durante el tratamiento. En los pacientes que sobrevivieron se observó que el examen micológico directo y AgPC de C. neoformans, en LCR y suero, permanecen positivos aún después de tratamiento y mejoría clínica del paciente.

This study evaluated the phenotypic tests used to differentiate Candida albicans from Candida dubliniensis. A total of 55 isolates from vaginal secretions, oral cavity and hemoculture were studied. They were originally identified as C. albicans, based on their morphological and physiological characteristics. These isolates were tested for colony color development on CHROMagar Candida medium, growth at 45 degrees C on Sabouraud Dextrose agar, lipolytic activity on Tween 80 Agar medium and colony morphology and chlamydoconidia formation on Staib agar medium. Of the 55 isolates studied, seven yielded one or more phenotypic characteristics suggestive of Candida dubliniensis. These isolates were tested by PCR with specific primers for Candida dubliniensis and API ID 32. The seven isolates were confirmed as Candida albicans. All of these finding indicate that DNA based tests should be used for definitive identification of Candida dubliniensis.

Con la finalidadde evaluar el uso del medio CHROMagar Candida en la rutina de identificacion de levaduras, se estudiaron 237 cepas obtenidas de sangre, orina, secrecion vaginal y otras muestras clinicas en el Centro de Referencia Bacteriologica del Hospital Universitario de Maracaibo, Estado Zulia (Venezuela), provenientes de 116 pacientes ambulatorios u hospitalizados, durante el periodo Marzo a Diciembre de 1999. Para la preparacion del medio de cultivo y la lectura del color de las colonias, se siguio la recomendacion del fabricante (CHROMagar Candida , Paris, France). De manera simultanea se realizaron pruebas de filamentizacion, fermentacion de carbohidratos y asimilacion de fuentes carbonadas y nitrogenadas; en algunos casos se utilizo el sistema API 20C. Los resultados mostraron una especificidad del 100% del medio CHROMagar Candida para la identificacion de Candida albicans (colonia verde), Candida tropicalis (colonia azul) y Candida krusei (colonia rosada). En tres muestras se pudo separar mas de una especie, esta diferenciacion se hizo facilmente cisible por los diferentes colores de las colonias. Este estudio corrobora la utilidad de este medio para la identificacion rapida de las principales especies del genero aisladas de material clinico.

Neurocryptococcosis was a rare nervous system infection. With the rising number of patients with AIDS it became a very frequent disease. This infection is supposed to infect patients with some kind of immunodeficiency and the CSF alterations often simulate tuberculous meningitis. The purpose of this research was to compare the CSF changes in AIDS and non-AIDS patients with meningoencephalitis caused by Cr. neoformans. There were analysed 41 CSF samples from non-AIDS patients with neurocryptococcosis and 23 CSF samples from AIDS patients with neurocryptococcosis. The results of this research allowed to conclude that the inflammatory changes in the CSF from AIDS patients showed a lower intensity compared to those non-AIDS patients. These results showed as well, that the CSF samples from non-AIDS patients always revealed some changes besides the yeast cells. In some samples of AIDS patients, however the unique change was the presence of the yeast. It was demonstrated also, that the presence of Cr. neoformans in CSF, not accompanied by any other change, may suggest that is a patient with AIDS. In non-AIDS patients CSF alterations often simulates tuberculous meningitis. However these alterations were rare in AIDS patients. The yeast cells were more numerous in CSF samples from AIDS patients than in those from non-AIDS patients Até a década de 80, antes do surgimento da AIDS, a criptococose era relativamente rara. Verificou-se que esta doença afeta muito frequentemente os pacientes com AIDS e pode ser a primeira manifestação desta síndrome. O objetivo deste trabalho é o de comparar o resultado dos exames das amostras do LCR inicial na meningencefalite por criptococo entre pacientes com e sem AIDS. Este trabalho é baseado no estudo de 41 pacientes com neurocriptococose sem AIDS e de 23 pacientes com neurocriptococose e AIDS. Este estudo permitiu verificar que a reação inflamatória, no sistema nervoso, quando presente, foi de menor intensidade nos pacientes com AIDS; a reação inflamatória esteve presente em todos os pacientes sem AIDS e ausente em 21,7% dos pacientes com AIDS; o quadro inflamatório crônico, semelhante ao da meningencefalite tuberculosa, clássico nas meningencefalites por criptococo, ocorreu raramente nos pacientes com AIDS; em média, o número de criptococos no LCR foi maior nos pacientes com AIDS; pode ser feito diagnóstico presuntivo da AIDS quando o criptococo estiver presente no LCR que não apresenta alterações citológicas e bioquímicas.

The immunochemical structure of the polysaccharide capsule of Cryptococcus neoformans has allowed definition of the serotypes of this yeast that have been designated A B C and D. The 2 varieties of C. neoformans have been classified as C. neoformans variety neoformans (comprised the A and D serotypes) and C. neoformans variety gattii (comprising the B and C serotypes) as well as their perfect states: Filobasidiella neoformans variety neoformans and Filobasidiella neoformans variety bacillispora. In a study including geographic areas of Europe Asia Africa Hawaii New Zealand and the Americas 70% of the isolates of C. neoformans corresponded to C. neoformans variety neoformans. In AIDS patients C. neoformans variety neoformans prevails. In Brazil in human samples of AIDS mostly from the state of Sao Paulo the B serotype made up 36%. Therefore in order to ascertain the prevalence of systemic mycotic cryptococcosis 28 isolates of C. neoformans obtained from AIDS and neurocryptococcosis patients (25 males and 3 females aged 15-55) in Sao Paulo were studied for 22 months. The serotyping of 25 isolates was carried out by the National Institutes of Health in Bethesda Maryland US using the agglutination technic. All tests yielded C. neoformans variety neoformans. The prevalence of A serotype was encountered in 22 (88%) of the cases the remaining 3 (11%) that could not be serotype owing to antigenetic deficiency also corresponded to the neoformans variety. These findings confirm the observation of other authors concerning AIDS patients. In Brazil only one case of C. neoformans variety gattii has been found in an AIDS patient with cryptococcosis in Rio de Janeiro. The predominance of C. neoformans variety neoformans in the isolates of AIDS patients in geographic areas previously known for high prevalence of C. neoformans variety gattii (Central Africa and California) is an enigma.