Wild-type minimum effective concentration distributions and epidemiologic cutoff values for caspofungin and Aspergillus spp. as determined by Clinical and Laboratory Standards Institute broth microdilution methods

Antifungal susceptibility testing of Aspergillus spp. against caspofungin has been standardized by the Clinical and Laboratory Standards Institute (CLSI). Recent studies have documented breakthrough infections with Aspergillus spp. for which the minimum effective concentration (MEC) for caspofungin ranged from 0.25 to 8 μg/mL. We tested a collection of 1590 clinical isolates of Aspergillus spp. (188 Aspergillus flavus, 1187 Aspergillus fumigatus, 114 Aspergillus niger, 71 Aspergillus terreus, and 30 Aspergillus versicolor) against caspofungin using the CLSI broth microdilution method. An epidemiologic cutoff value (ECV) of ≤0.06 μg/mL encompassed the wild-type (WT) MEC distribution (percentage of MECs) of A. flavus (99.5%), A. fumigatus (98.7%), A. niger (100%), and A. terreus (97.2%), and an ECV of ≤0.12 μg/mL encompassed the WT distribution of A. versicolor (96.7%). A total of 20 strains showed MECs that were outside the ECVs: 1 A. flavus (0.12 μg/mL), 16 A. fumigatus (0.12 μg/mL [13], 1 μg/mL [1], 2 μg/mL [2]), 2 A. terreus (0.12 [1] and >8 μg/mL [1]), and 1 A. versicolor (4 μg/mL). The establishment of the WT MEC distributions and ECVs for caspofungin and the major species of Aspergillus will be useful in resistance surveillance and is an important step toward the development of clinical breakpoints.