Role of FKS Mutations in Candida glabrata: MIC Values, Echinocandin Resistance, and Multidrug Resistance

• Type of Material: Article
• Authors: Cau D. Pham, Centers for Disease Control and Prevention; Naureen Iqbal, Centers for Disease Control and Prevention; Carol B. Bolden, Centers for Disease Control and Prevention; Randall J. Kuykendall, Centers for Disease Control and Prevention; Lee H. Harrison, Johns Hopkins University; Monica Farley, Emory University; William Schaffner, Vanderbilt University; Zintars G. Beldavs, Oregon Public Health Authority; Tom Chiller, Emory University; Benjamin J. Park, Centers for Disease Control and Prevention; Angela A. Cleveland, Centers for Disease Control and Prevention; Shawn R. Lockhart, Centers for Disease Control and Prevention
• Language: English
• Date: 2014-08-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2014, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/AAC.03255-14
• Title of Journal or Parent Work: Antimicrobial Agents and Chemotherapy
• ISSN: 0066-4804
• Volume: 58
• Issue: 8
• Start Page: 4690
• End Page: 4696
• Keywords: CASPOFUNGIN RESISTANCE; SPECIES IDENTIFICATION; Pharmacology & Pharmacy; INVASIVE CANDIDIASIS; MICAFUNGIN; POPULATION-BASED SURVEILLANCE; ANTIFUNGAL SUSCEPTIBILITY; Microbiology; Science & Technology; BLOOD-STREAM INFECTIONS; PROLONGED THERAPY; MICROBIOLOGY; Life Sciences & Biomedicine; PHARMACOLOGY & PHARMACY; RISK-FACTOR; AMPHOTERICIN-B
• Research Categories: Health Sciences, Public Health; Biology, Microbiology

Abstract

Candida glabrata is the second leading cause of candidemia in U.S. hospitals. Current guidelines suggest that an echinocandin be used as the primary therapy for the treatment of C. glabrata disease due to the high rate of resistance to fluconazole. Recent case reports indicate that C. glabrata resistance to echinocandins may be increasing. We performed susceptibility testing on 1,380 isolates of C. glabrata collected between 2008 and 2013 from four U.S. cities, Atlanta, Baltimore, Knoxville, and Portland. Our analysis showed that 3.1%, 3.3%, and 3.6% of the isolates were resistant to anidulafungin, caspofungin, and micafungin, respectively. We screened 1,032 of these isolates, including all 77 that had either a resistant or intermediate MIC value with respect to at least one echinocandin, for mutations in the hot spot regions of FKS1 and FKS2, the major mechanism of echinocandin resistance. Fifty-one isolates were identified with hot spot mutations, 16 in FKS1 and 35 in FKS2. All of the isolates with an FKS mutation except one were resistant to at least one echinocandin by susceptibility testing. Of the isolates resistant to at least one echinocandin, 36% were also resistant to fluconazole. Echinocandin resistance among U.S. C. glabrata isolates is a concern, especially in light of the fact that one-third of those isolates may be multidrug resistant. Further monitoring of U.S. C. glabrata isolates for echinocandin resistance is warranted.