In Vitro Susceptibility of Invasive Isolates of Candida spp. to Anidulafungin, Caspofungin, and Micafungin: Six Years of Global Surveillance

Abstract

Volume 46, no. 1, p. 150-156, 2008. In our recent report describing the in vitro susceptibility of 5,346 Candida spp. to the echinocandins, we noted the excellent activity of the echinocandins and the lack of evidence of emerging echinocandin resistance over 6 years of global surveillance. We also described 12 (out of a total of 2,869) isolates of Candida albicans that demonstrated a high-anidulafungin-MIC phenotype, which we defined as an anidulafungin MIC of 2 g/ml. We noted that these isolates, while still susceptible according to the recently approved Clinical and Laboratory Standards Institute (CLSI) breakpoint of Յ2 g/ml (minutes of the June 2007 meeting of the CLSI Antifungal Subcommittee), were nonetheless of interest because their echinocandin MICs were distinctly higher than the normal wild-type distribution of echinocandin MICs for C. albicans (page 152, column 2, lines 1-18).While pulling these 12 isolates from our bank for further evaluation, we noted that none of them demonstrated the characteristic green color of C. albicans on CHROMagar Candida ( Further evaluation of these isolates (with the assistance of David Pincus and Nancy Moss in the research and development group at bioMerieux, Inc.) revealed that all demonstrated the same atypical pattern for the Vitek YBC database (for C. parapsilosis), specifically for three reactions, those involving alpha methyl-D-glucoside (AMG), melezitose (MLZ), and xylitol (XLT). All 12 isolates were AMG negative, MLZ negative, and XLT positive in our hands. Based upon these three atypical reactions, the YBC algorithm generated C. albicans as the best match for each isolate. These findings were confirmed by sending the isolates to bioMerieux, Inc., for testing, which revealed highly variable AMG statuses (with only 3 of the 12 isolates being strongly negative), negative MLZ results for 11 of the 12 isolates, and positive XLT results for all 12 isolates. When tested with the API 20-C system, 11 of the 12 isolates were correctly identified as C. parapsilosis, and when tested on the Vitek 2 YST card, all 12 were correctly identified, with 3 of the 12 giving a "low discrimination" call with C. famata.We regret that we did not detect this species identification error prior to publication. At the time of the initial receipt and characterization of the isolates, all were identified as C. albicans based upon the Vitek YBC result. We are in the process of systematically assessing the error rate of our Vitek YBC system for identification of C. parapsilosis, in particular the rare misidentification of C. parapsilosis as C. albicans. Preliminary findings suggest that this is an uncommon event, occurring for fewer than 2% of all C. parapsilosis isolates tested on the YBC (data not shown). In each case of misidentification we have detected thus far, the CHROMagar appearance of the organism is not consistent with that of C. albicans. We no longer accept a Vitek YBC result of C. albicans for an isolate without a characteristic CHROMagar appearance. In addition, we confirm the id...

Susceptibilidad in vitro a anidulafungina en 100 cepas de especies de Candida aisladas previo a la introducción de esta equinocandina en Chile

“…**: CIM ≤ 2 μg/mL es considerado como sensible 17 . S= sensible; SDD= sensible dosis dependiente; R= resistente.…”

“…El estudio de la susceptibilidad in vitro a anidulafungina evidenció 100% de sensibilidad, resultado comparable con un estudio de Pfaller y cols (2008), donde se analizaron 5.346 cepas con 98,8% de sensibilidad. Del total de cepas analizadas, la CIM 50 y la CIM 90 refl ejan in vitro un rango para uso terapéutico seguro, siendo comparable con el estudio previamente mencionado, donde los valores de CIM 50 y CIM 90 fue de 0,06 y 2 μg/mL, respectivamente 17 .…”

“…Los antifúngicos de esta clase, como anidulafungina, caspofungina y micafungina, poseen actividad contra muchas especies del género Candida, incluyendo cepas resistentes a polienos y a azoles, transformándose en una excelente alternativa terapéutica frente a cepas resistentes a otros antimicóticos [13][14][15] . Los integrantes de esta familia de antifúngicos tienen una alta actividad in vitro asociada con una baja toxicidad en el tratamiento de infecciones graves por Candida 16,17 . Entre estos fármacos, anidulafungina ha sido aprobada en Estados Unidos de América por la FDA (Food and Drug Administration) en el año 2006 para el tratamiento de la candidiasis invasora, incluyendo candidemia 18 .…”

Equinocandinas

“…En la Tabla 1 se muestran los resultados de más de 5.000 cepas de Candida spp, recolectados en 90 centros médicos norteamericanos, desde enero del 2001 hasta diciembre de 2006, usando la técnica desarrollada por el Instituto de Estándares Clínicos y de Laboratorio de Estados Unidos (CLSI, por sus siglas en inglés). De las cepas identifi cadas 54% correspondían a C. albicans, 14% a C. parapsilopsis, 3% a C .glabrata, y, fi nalmente, 1% a C. krusei 16 . Más de 99% de las cepas fueron inhibidas por una concentración del antifúngico < 2 μg/ml, de las tres equinocandinas.…”

“…En sólo seis cepas (0,15% de los cultivos) se encontró una CIM mayor a 4 μg/ml, la cual correspondía a C. guilliermondii, C. glabrata y C. tropicalis, estas últimas con resistencia a caspofungina. Candida rugosa presentó una CIM elevada para anidulafungina 16 .…”