Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method

ESPINEL-INGROF A; ARENDRUP, MAIKEN CAVLING; CANTON, E; CORDOBA, S; DANNAOUI, E; GARCIA-RODRIGUEZ, J; GONZALEZ, GM; GOVENDER, NP; MARTIN-MANZUELOS, E; LASS-FLÖRL, CORNELIA; LINARES SICILIA, MJ; RODRIGUEZ-IGLESIAS, MA; PELAEZ, T; SHIELDS, R; GARCIA, GUILLERMO; GUINEA, J; SANGUINETTI, M; TURNIDGE, J

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2016

0066-4804

Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of thestatistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans;0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8,4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalisThe amphotericin B ECV was 0.25 μg/ml for C. dubliniensis and 2, 8, 2, and 16μg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus,respectively. While anidulafungin Etest ECVs classified 92% of the Candida fksmutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandinsurrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using theEtest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.