Wild-Type MIC Distributions and Epidemiological Cutoff Values for Posaconazole and Voriconazole and Candida spp. as Determined by 24-Hour CLSI Broth Microdilution

Abstract

ABSTRACT We tested 16,191 strains of Candida against posaconazole and voriconazole, using the CLSI M27-A3 broth microdilution (BMD) method (24-h incubation), in order to define wild-type (WT) populations and epidemiological cutoff values (ECVs). From 2001 to 2009, 8,619 isolates of Candida albicans , 2,415 isolates of C. glabrata , 2,278 isolates of C. parapsilosis , 1,895 isolates of C. tropicalis , 508 isolates of C. krusei , 205 isolates of C. lusitaniae , 177 isolates of C. guilliermondii , and 93 isolates of C. kefyr were obtained from over 100 centers worldwide. The modal MICs (μg/ml) for posaconazole and voriconazole, respectively, were as follows: for C. albicans , 0.016 and 0.007; for C. glabrata , 0.5 and 0.06; for C. parapsilosis , 0.06 and 0.007; for C. tropicalis , 0.03 and 0.015; for C. krusei , 0.25 and 0.12; for C. lusitaniae , 0.03 and 0.007; for C. guilliermondii , 0.12 and 0.03; and for C. kefyr , 0.06 and 0.007. The ECVs (μg/ml [% of isolates that had MICs equal to or less than the ECV]) for posaconazole and voriconazole, respectively, were as follows: 0.06 (98.5) and 0.03 (98.9) for C. albicans , 2 (96.2) and 0.5 (90.4%) for C. glabrata , 0.25 (99.3) and 0.12 (97.9) for C. parapsilosis , 0.12 (97.6) and 0.06 (97.2) for C. tropicalis , 0.5 (99.8) and 0.5 (99.4) for C. krusei , 0.12 (95.6) and 0.03 (96.6) for C. lusitaniae , 0.5 (98.9) and 0.25 (98.3) for C. guilliermondii , and 0.25 (100.0) and 0.015 (100.0) for C. kefyr . In the absence of clinical breakpoints (CBPs) for posaconazole, these WT distributions and ECVs will be useful in surveillance for emergence of reduced susceptibility to posaconazole among Candida spp. Whereas a CBP for susceptibility of ≤1 μg/ml has been established for voriconazole and all species of Candida , it is notable that ECVs for this agent range from 10- to >100-fold lower than the CBP, depending on the species of Candida . The CBP is inadequate in detecting the emergence of voriconazole resistance among most Candida species encountered clinically. The CBPs for voriconazole should be reassessed, with consideration for development of species-specific CBPs.