Interlaboratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: Should the clinical laboratory be testing this agent?
Antimicrob Agents Chemother. 2013 Sep 9;
Authors: Espinel-Ingroff A, Arendrup MC, Pfaller MA, Bonfietti LX, Bustamante B, Canton E, Chryssanthou E, Cuenca-Estrella M, Dannaoui E, Fothergill A, Fuller J, Gaustad P, Gonzalez GM, Guarro J, Lass-Flörl C, Lockhart SR, Meis JF, Moore CB, Ostrosky-Zeichner L, Pelaez T, Pukinskas SR, St-Germain G, Szeszs MW, Turnidge J
Although CLSI clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candida spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550 Candida isolates 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: 0.016-0.5 μg/ml for C. albicans and C. tropicalis; 0.031-0.5 μg/ml for C. glabrata; 0.063-1 μg/ml for C. krusei; variability was also similar among C. dubliniensis and C. lusitaniae. The exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where most modes were within one twofold dilution of each other. These findings were consistent with available EUCAST data (403 to 2,556 MICs) for C. albicans, C. glabrata, C. krusei, and C. 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] (e.g., C. glabrata and C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candida is not recommended; micafungin or anidulafungin data could be used instead.
PMID: 24018263 [PubMed - as supplied by publisher]