title: Use of micafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 3,764 clinical isolates of Candida by use of CLSI methods and interpretive criteria.
abstract: Due to unacceptably high interlaboratory variation in caspofungin MIC values, we evaluated the use of micafungin as a surrogate marker to predict the susceptibility of Candida spp. to caspofungin using reference methods and species-specific interpretive criteria. The MIC results for 3,764 strains of Candida (eight species), including 73 strains with fks mutations, were used. Caspofungin MIC values and species-specific interpretive criteria were compared with those of micafungin to determine the percent categorical agreement (%CA) and very major error (VME), major error (ME), and minor error rates as well as their ability to detect fks mutant strains of Candida albicans (11 mutants), Candida tropicalis (4 mutants), Candida krusei (3 mutants), and Candida glabrata (55 mutants). Overall, the %CA was 98.8% (0.2% VMEs and MEs, 0.8% minor errors) using micafungin as the surrogate marker. Among the 60 isolates of C. albicans (9 isolates), C. tropicalis (5 isolates), C. krusei (2 isolates), and C. glabrata (44 isolates) that were nonsusceptible (either intermediate or resistant) to both caspofungin and micafungin, 54 (90.0%) contained a mutation in fks1 or fks2. An additional 10 C. glabrata mutants, two C. albicans mutants, and one mutant each of C. tropicalis and C. krusei were classified as susceptible to both antifungal agents. Using the epidemiological cutoff values (ECVs) of 0.12 μg/ml for caspofungin and 0.03 μg/ml for micafungin to differentiate wild-type (WT) from non-WT strains of C. glabrata, 80% of the C. glabrata mutants were non-WT for both agents (96% concordance). Micafungin may serve as an acceptable surrogate marker for the prediction of susceptibility and resistance of Candida to caspofungin.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pfaller
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Messer
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Diekema
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D015415:Biomarkers; D002175:Candida / Q000187:drug effects* / Q000235:genetics; D000077336:Caspofungin; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D000077336:Caspofungin; D000077551:Micafungin