Low and constant micafungin concentrations may be sufficient to lead to resistance mutations in FKS2 gene of Candida glabrata.

We studied the ability of five echinocandin-susceptible C. glabrata isolates to acquire in vitro resistance to anidulafungin and micafungin. All isolates became phenotypically resistant after 2-4 days of exposure to low and constant micafungin concentrations (P<.05). Mutations in the HS1 region of the FKS2 gene were found in all isolates. The acquisition of resistance was not related to the previous use of antifungal treatment in the patients or the presence of mutations at MSH2 gene. We found differences (P<.0001) in the median survival of Galleria mellonella larvae infected with FKS2 mutant isolates (5 days) and wild-type isolates (3 days).