Multilaboratory Study of Epidemiological Cutoff Values for Detection of Resistance in Eight Candida Species to Fluconazole, Posaconazole, and Voriconazole

Abstract

uAlthough epidemiological cutoff values (ECVs) have been established for Candida spp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eight Candida species and fluconazole, posaconazole, and voriconazole based on wild-type (WT) MIC distributions for isolates of C. albicans (n ‫؍‬ 11,241 isolates), C. glabrata (7,538), C. parapsilosis (6,023), C. tropicalis (3,748), C. krusei (1,073), C. lusitaniae (574), C. guilliermondii (373), and C. dubliniensis (162). The 24-h CLSI broth microdilution MICs were collated from multiple laboratories (in Canada, Brazil, Europe, Mexico, Peru, and the United States). The ECVs for distributions originating from >6 laboratories, which included >95% of the modeled WT population, for fluconazole, posaconazole, and voriconazole were, respectively, 0.5, 0.06 and 0.03 g/ml for C. albicans, 0.5, 0.25, and 0.03 g/ml for C. dubliniensis, 8, 1, and 0.25 g/ml for C. glabrata, 8, 0.5, and 0.12 g/ml for C. guilliermondii, 32, 0.5, and 0.25 g/ml for C. krusei, 1, 0.06, and 0.06 g/ml for C. lusitaniae, 1, 0.25, and 0.03 g/ml for C. parapsilosis, and 1, 0.12, and 0.06 g/ml for C. tropicalis. The low number of MICs (<100) for other less prevalent species (C. famata, C. kefyr, C. orthopsilosis, C. rugosa) precluded ECV definition, but their MIC distributions are documented. Evaluation of our ECVs for some species/ agent combinations using published individual MICs for 136 isolates (harboring mutations in or upregulation of ERG11, MDR1, CDR1, or CDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates.

Antifungal Susceptibility Profiles of Bloodstream Yeast Isolates by Sensititre YeastOne over Nine Years at a Large Italian Teaching Hospital

“…This provides further support for the concept that posaconazole ECVs for C. krusei and other common species of Candida may be set too low, perhaps because the ECVs were derived from MIC distributions which were obtained from a single laboratory (30). However, ECVs for MIC distributions originating from Ն6 laboratories for posaconazole remained substantially unchanged for eight species of Candida, including C. albicans, C. tropicalis, and C. krusei (46).…”

Multicenter Study of Epidemiological Cutoff Values and Detection of Resistance in Candida spp. to Anidulafungin, Caspofungin, and Micafungin Using the Sensititre YeastOne Colorimetric Method

“…Since the SYO panel also provides MICs for the other two echinocandins, SYO ECVs for anidulafungin and micafungin would be useful for laboratories using this method. The ECV is the highest endpoint of the MIC distribution of the wild-type (WT) population and is established using MIC distributions from multiple laboratories (at least 3 laboratories and 100 MICs/species/agent) (13,16,17). ECV surveillance may detect the emergence of in vitro resistance or distinguish between phenotypic WT isolates (isolates with no detectable phenotypic resistance) and non-WT isolates (isolates with mechanisms of resistance) (13,(16)(17)(18).…”

Multicenter Evaluation of the New Vitek 2 Yeast Susceptibility Test Using New CLSI Clinical Breakpoints for Fluconazole

“…All isolates of C. krusei are considered to be R to fluconazole, irrespective of the MIC. Because of the lack of CBPs for the less common species of Candida and C. neoformans (14), the ECVs of fluconazole were used for C. lusitaniae (1 g/ml), C. dubliniensis (0.5 g/ml), C. guilliermondii (8 g/ ml), C. pelliculosa (4 g/ml), C. kefyr (1 g/ml), and C. neoformans (16 g/ml) to categorize isolates of these species as wild type (WT; MIC, ՅECV) or non-WT (MIC, ϾECV) (11,12,14). VME were identified when the reference CLSI BMD MIC indicated an R or non-WT result and the Vitek 2 MIC was S or WT.…”

“…Several studies have demonstrated excellent essential agreement (EA; within 2 dilutions) and categorical agreement (CA; susceptibility results that fall within the same interpretive category) between the Vitek 2 and CLSI BMD methods for testing fluconazole against Candida species and C. neoformans (4-9). All of these studies were performed prior to the adoption by the CLSI of new (lower), species-specific clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) of fluconazole for several species of Candida and C. neoformans (10)(11)(12)(13)(14). Pfaller et al (15) reanalyzed the original data from a previous study (7) by using the new CBPs and ECVs of fluconazole and found that the CA between the Vitek 2 and CLSI BMD methods was 96.8% with no very major errors (VME) and only 1.3% major errors (ME) (15).…”

“…All of these studies were performed prior to the adoption by the CLSI of new (lower), species-specific clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) of fluconazole for several species of Candida and C. neoformans (10)(11)(12)(13)(14). Pfaller et al (15) reanalyzed the original data from a previous study (7) by using the new CBPs and ECVs of fluconazole and found that the CA between the Vitek 2 and CLSI BMD methods was 96.8% with no very major errors (VME) and only 1.3% major errors (ME) (15).…”