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 g/ml were considered resistant. Strains for which anidulafungin and caspofungin MICs were >0.5 g/ml and for which micafungin MICs were >0.25 g/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 g/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.

Candidaemia in a tertiary care academic hospital in Italy. The impact of C. parapsilosis complex on the species distribution and antifungal susceptibility

“…In fact, while the resistance of C. albicans to echinocandins was limited to two strains, that of C. glabrata ranged between 7.32 % for micafungin and anidulafungin through to 8.89 % for caspofungin. As evidenced by Pfaller et al [31] the mutation in the hot spot (HS) regions of the FKS gene that encodes the target enzyme (glycan synthase) for echinocandins may lead to MICs of anidulafungin, caspofungin and micafungin that are greater than the CBPs or ECVs for C. glabrata. However, these observations do not fully explain the increasing resistance rates in our hospital and, since we had no further data on antifungal use, it is difficult to draw any further conclusions.…”

Development of a Luminex-Based Multiplex Assay for Detection of Mutations Conferring Resistance to Echinocandins in Candida glabrata

“…With a large proportion of isolates resistant to fluconazole, echinocandins are the treatment of choice recommended by the Infectious Disease Society of America for candidemia caused by C. glabrata (3). However, as has happened with fluconazole, increased usage of echinocandins has demonstrated the ability of C. glabrata to occasionally develop resistance (4)(5)(6)(7)(8)(9)(10). With echinocandins recommended for use as empirical therapy for C. glabrata infections in U.S. hospitals, rapid identification of isolates which may be echinocandin resistant has increasing clinical relevancy.…”

Rapid Detection of FKS -Associated Echinocandin Resistance in Candida glabrata

“…With rapidly expanded usage of echinocandins, the first-line therapy for invasive candidiasis, an alarming trend of rising echinocandin resistance in C. glabrata has posed a serious clinical challenge (4)(5)(6). Detection of echinocandin resistance can be assessed phenotypically, using either microdilution or disc diffusion MIC assays performed in accordance with guidance of the Clinical and Laboratory Standards Institute (CLSI) M27-A3 standard (7) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) Definitive Document Edef 7.2 (8).…”