Use of Epidemiological Cutoff Values To Examine 9-Year Trends in Susceptibility of Candida Species to Anidulafungin, Caspofungin, and Micafungin

Abstract

ABSTRACT The CLSI clinical breakpoint (CBP) for echinocandin susceptibility (S; MICs of ≤2 μg/ml) may classify isolates with acquired resistance (R) mutations as susceptible. Epidemiological cutoff values (ECVs) have been established to distinguish wild-type (WT) Candida strains from those that may exhibit R mutations. The CLSI-developed ECVs for anidulafungin, caspofungin, and micafungin were applied to 15,269 isolates of Candida spp. collected from over 100 centers worldwide between 2001 and 2009 to determine the frequency of non-WT strains of each species. The collection included 8,378 isolates of Candida albicans , 2,352 isolates of C. glabrata , 2,195 isolates of C. parapsilosis , 1,841 isolates of C. tropicalis , and 503 isolates of C. krusei . The mean percentages of non-WT isolates per year for anidulafungin, caspofungin, and micafungin, respectively, were as follows: for C. albicans , 0.3, 0.1, and 2.1; for C. glabrata , 0.8, 1.3, and 1.6; for C. parapsilosis , 0.0, 1.5, and 0.5; for C. tropicalis , 0.9, 0.7, and 0.9; and for C. krusei , 0.5, 6.4, and 3.5. We noted increases in the percentage of non-WT isolates, from 0.5% (2001) to 3.1% (2009) for caspofungin and C. parapsilosis , from 0.4% (2004) to 1.8% (2009) for anidulafungin and C. glabrata , from 2.4% (2004) to 5.7% (2009) for micafungin and C. krusei , and from 0.0% (2004) to 3.1% (2009) for micafungin and C. parapsilosis . No trends were noted for any species and drug when we used the CBP. Echinocandin CBPs are insensitive for detecting emerging R. Although uncommon, decreased S among Candida isolates was observed for each of the echinocandins and varied by species. Using ECVs is important in determining R trends among echinocandins and Candida .