Interlaboratory Variability of Caspofungin MICs for Candida spp. Using CLSI and EUCAST Methods: Should the Clinical Laboratory Be Testing This Agent?

Abstract

ABSTRACTAlthough Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs forCandidaspp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550Candidaisolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 μg/ml forC. albicansandC. tropicalis, 0.031 to 0.5 μg/ml forC. glabrata, and 0.063 to 1 μg/ml forC. krusei. Variability was also similar among MIC distributions forC. dubliniensisandC. lusitaniae. The exceptions wereC. parapsilosisandC. guilliermondiiMIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) forC. albicans,C. glabrata,C. krusei, andC. tropicalis. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g.,C. glabrataandC. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs forCandidais not recommended; micafungin or anidulafungin data could be used instead.