Interlaboratory variability of Caspofungin MICs for Candida spp. Using CLSI and EUCAST methods: should the clinical laboratory be testing this agent?

Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candida spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550 Candida isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 µg/ml for C. albicans and C. tropicalis, 0.031 to 0.5 µg/ml for C. glabrata, and 0.063 to 1 µg/ml for C. krusei. Variability was also similar among MIC distributions for C. dubliniensis and C. lusitaniae. The exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for C. albicans, C. glabrata, C. krusei, and C. tropicalis. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g., C. glabrata and C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candida is not recommended; micafungin or anidulafungin data could be used instead.

Ten-year study of species distribution and antifungal susceptibilities of Candida bloodstream isolates at a Brazilian tertiary hospital.

To describe the incidence and susceptibility profile of Candida bloodstream infections in a tertiary-care hospital, we performed a retrospective observational study from 1998 to 2007. Comorbidities and risk factors were compiled from all cases. In vitro susceptibility testing to fluconazole, itraconazole, voriconazole, and amphotericin B was performed for 100 isolates, and caspofungin was tested for C. parapsilosis complex. In a ten-year evaluation of candidemias, 44 % were caused by C. albicans, and species of the C. parapsilosis complex were the second most frequent agents (37 %). Other species presented lower incidences (C. tropicalis, 13 %, C. glabrata, 5 %, and C. krusei, 1 %). Neither C. dubliniensis nor C. metapsilosis were observed in this study. C. orthopsilosis (3 %) and C. parapsilosis stricto sensu (34 %) were also found. Species distribution was independent of catheterization, mechanical ventilation, or previous use of antifungals or corticoids. Parenteral nutrition administration was strongly related to C. glabrata infection, and the highest mortality (80 %) was observed in patients infected by this species. All C. albicans isolates showed high susceptibility to all tested drugs. However, two C. parapsilosis stricto sensu isolates presented high minimum inhibitory concentration (MIC) (4 mg/L each) to fluconazole, and one exhibited voriconazole MIC of 0.25 mg/L, highlighting the cross-resistance to these azoles. All isolates of C. tropicalis and C. glabrata showed no resistance to any drug tested. No difference was noted between C. parapsilosis and C. orthopsilosis susceptibilities to caspofungin. Our results suggest that resistance to amphotericin B, fluconazole, voriconazole, itraconazole, and caspofungin in Brazilian Candida bloodstream isolates is still uncommon.

Epidemiologia de candidíase hospitalar: importância da identificação específica / Epidemiology of nosocomial candidiasis: the importance of specific identification

Infecções fúngicas sistêmicas são hoje importante causa de morbidade e mortalidade em pacientes imunossuprimidos ou com outras condições predisponentes. Candida albicans e as não-albicans são importante causa de infecções nosocomiais e vários destes agentes são menos suscetíveis às drogas antifúngicas, principalmente os azólicos, um fato que tem significado no tratamento destes pacientes. O moderno laboratório de micologia tem importante papel no esclarecimento destas infecções, incluindo sua detecção , identificação e a sensibilidade a drogas antifúngicas, bem como a análise epidemiológica. Neste estudo, foi comparada a distribuição de espécies de Candida relacionadas a fungemias e outras fontes, em quatro hospitais do Estado de São Paulo. Das 40 leveduras identificadas, C. albicans, C. parapsilosis e C. tropicalis foram isoladas, respectivamente, em 35 por cento, 50 por cento e 15 por cento, revelando uma tendência de ser maior a freqüência de espécies não-albicans. As fungemias foram causadas por C. parapsilosis (45,4 por cento). C. albicans (36,4 por cento) e C. tropicalis (18,2 por cento), o que revela um aumento de espécies não-albicans em relação a séries históricas. As três diferentes espécies foram incluídas em 6,3 e 4 biótipos diferentes, respectivamente para C.albicans, C.parapsilosis e C.tropicalis. Este estudo enfatiza a importância da avaliação de espécies de Candida especialmente em centros hospitalares com pacientes de risco.