LAUSR

Candida glabrata readily develops resistance to echinocandins. Identification, antifungal susceptibility testing (AST) and resistance mechanism to echinocandins among C. glabrata was determined in Kuwait. C. glabrata isolates (n = 75) were tested by Vitek2, multiplex PCR and/or PCR-sequencing of rDNA. AST to fluconazole, caspofungin, micafungin and amphotericin B was determined by Etest and to micafungin by broth microdilution (BMD). Mutations in hotspot-1/hotspot-2 of FKS1/FKS2 and ERG11 were detected by PCR-sequencing. All isolates were identified as C. glabrata sensu stricto. Seventy isolates were susceptible and five were resistant to micafungin by Etest and BMD (essential agreement, 93%; categorical agreement, 100%). Three micafungin-resistant isolates were resistant and two were susceptible dose-dependent to caspofungin. Four and one micafungin-resistant isolate contained S663P and ∆659 F mutation, respectively, in hotspot-1 of FKS2. Micafungin-resistant isolates were genotypically distinct strains. Only one of 36 fluconazole-resistant isolate contained nonsynonymous ERG11 mutations. Thirty-four of 36 fluconazole-resistant isolates were genotypically distinct strains. Our data show that micafungin susceptibility reliably identifies echinocandin-resistant isolates and may serve as a surrogate marker for predicting susceptibility/resistance of C. glabrata to caspofungin. All micafungin-resistant isolates also harbored a nonsynonymous/deletion mutation in hotspot-1 of FKS2. Fingerprinting data showed that echinocandin/fluconazole resistance development in C. glabrata is not clonal.