title: Role of FKS Mutations in Candida glabrata: MIC values, echinocandin resistance, and multidrug resistance.
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.
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Cau D
authors.initials: CD
authors.lastname: Pham
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Naureen
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Carol B
authors.initials: CB
authors.lastname: Bolden
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Kuykendall
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Lee H
authors.initials: LH
authors.lastname: Harrison
authors.affiliation: Georgia Emerging Infections Program, Atlanta Veterans Affairs Medical Center and Emory University, Atlanta, Georgia, USA.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Farley
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: William
authors.initials: W
authors.lastname: Schaffner
authors.affiliation: Oregon Public Health Authority, Portland, Oregon, USA.
authors.forename: Zintars G
authors.initials: ZG
authors.lastname: Beldavs
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Tom M
authors.initials: TM
authors.lastname: Chiller
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Park
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Angela A
authors.initials: AA
authors.lastname: Cleveland
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA gyi2@cdc.gov.
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockhart
mesh_terms: D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D058387:Candidemia / Q000188:drug therapy / Q000382:microbiology; D000077336:Caspofungin; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D054714:Echinocandins / Q000494:pharmacology; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics* / Q000378:metabolism; D055666:Lipopeptides / Q000494:pharmacology; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D009154:Mutation; D014481:United States
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D015725:Fluconazole; D000077612:Anidulafungin; D005964:Glucosyltransferases; D000077336:Caspofungin; D000077551:Micafungin