Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata

Abstract

The echinocandin class of antifungal agents is considered to be the first-line treatment of bloodstream infections (BSI) due to Candida glabrata. Recent reports of BSI due to strains of C. glabrata resistant to both fluconazole and the echinocandins are of concern and prompted us to review the experience of two large surveillance programs, the SENTRY Antimicrobial Surveillance Program for the years 2006 through 2010 and the Centers for Disease Control and Prevention population-based surveillance conducted in 2008 to 2010. The in vitro susceptibilities of 1,669 BSI isolates of C. glabrata to fluconazole, voriconazole, anidulafungin, caspofungin, and micafungin were determined by CLSI broth microdilution methods. Fluconazole MICs of ≥64 μg/ml were considered resistant. Strains for which anidulafungin and caspofungin MICs were ≥0.5 μg/ml and for which micafungin MICs were ≥0.25 μg/ml were considered resistant. A total of 162 isolates (9.7%) were resistant to fluconazole, of which 98.8% were nonsusceptible to voriconazole (MIC > 0.5 μg/ml) and 9.3%, 9.3%, and 8.0% were resistant to anidulafungin, caspofungin, and micafungin, respectively. There were 18 fluconazole-resistant isolates that were resistant to one or more of the echinocandins (11.1% of all fluconazole-resistant isolates), all of which contained an acquired mutation in fks1 or fks2. By comparison, there were no echinocandin-resistant strains detected among 110 fluconazole-resistant isolates of C. glabrata tested in 2001 to 2004. These data document the broad emergence of coresistance over time to both azoles and echinocandins in clinical isolates of C. glabrata.