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

We tested 16,191 strains ofCandida 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 ofCandida albicans , 2,415 isolates ofC. glabrata , 2,278 isolates ofC. parapsilosis , 1,895 isolates ofC. tropicalis , 508 isolates ofC. krusei , 205 isolates ofC. lusitaniae , 177 isolates ofC. guilliermondii , and 93 isolates ofC. kefyr were obtained from over 100 centers worldwide. The modal MICs (μg/ml) for posaconazole and voriconazole, respectively, were as follows: forC. albicans , 0.016 and 0.007; forC. glabrata , 0.5 and 0.06; forC. parapsilosis , 0.06 and 0.007; forC. tropicalis , 0.03 and 0.015; forC. krusei , 0.25 and 0.12; forC. lusitaniae , 0.03 and 0.007; forC. guilliermondii , 0.12 and 0.03; and forC. 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) forC. albicans , 2 (96.2) and 0.5 (90.4%) forC. glabrata , 0.25 (99.3) and 0.12 (97.9) forC. parapsilosis , 0.12 (97.6) and 0.06 (97.2) forC. tropicalis , 0.5 (99.8) and 0.5 (99.4) forC. krusei , 0.12 (95.6) and 0.03 (96.6) forC. lusitaniae , 0.5 (98.9) and 0.25 (98.3) forC. guilliermondii , and 0.25 (100.0) and 0.015 (100.0) forC. 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 amongCandida spp. Whereas a CBP for susceptibility of ≤1 μg/ml has been established for voriconazole and all species ofCandida , it is notable that ECVs for this agent range from 10- to >100-fold lower than the CBP, depending on the species ofCandida . The CBP is inadequate in detecting the emergence of voriconazole resistance among mostCandida species encountered clinically. The CBPs for voriconazole should be reassessed, with consideration for development of species-specific CBPs.