title: Epidemiology and Risk Factors for Echinocandin Nonsusceptible Candida glabrata Bloodstream Infections: Data From a Large Multisite Population-Based Candidemia Surveillance Program, 2008-2014.
abstract: Background.  Echinocandins are first-line treatment for Candida glabrata candidemia. Echinocandin resistance is concerning due to limited remaining treatment options. We used data from a multisite, population-based surveillance program to describe the epidemiology and risk factors for echinocandin nonsusceptible (NS) C glabrata candidemia. Methods.  The Centers for Disease Control and Prevention's Emerging Infections Program conducts population-based laboratory surveillance for candidemia in 4 metropolitan areas (7.9 million persons; 80 hospitals). We identified C glabrata cases occurring during 2008-2014; medical records of cases were reviewed, and C glabrata isolates underwent broth microdilution antifungal susceptibility testing. We defined echinocandin-NS C glabrata (intermediate or resistant) based on 2012 Clinical and Laboratory Standards Institute minimum inhibitory concentration breakpoints. Independent risk factors for NS C glabrata were determined by stepwise logistic regression. Results.  Of 1385 C glabrata cases, 83 (6.0%) had NS isolates (19 intermediate and 64 resistant); the proportion of NS isolates rose from 4.2% in 2008 to 7.8% in 2014 (P < .001). The proportion of NS isolates at each hospital ranged from 0% to 25.8%; 3 large, academic hospitals accounted for almost half of all NS isolates. In multivariate analysis, prior echinocandin exposure (adjusted odds ratio [aOR], 5.3; 95% CI, 2.6-1.2), previous candidemia episode (aOR, 2.5; 95% CI, 1.2-5.1), hospitalization in the last 90 days (aOR, 1.9; 95% CI, 1.0-3.5, and fluconazole resistance [aOR, 3.6; 95% CI, 2.0-6.4]) were significantly associated with NS C glabrata. Fifty-nine percent of NS C glabrata cases had no known prior echinocandin exposure. Conclusion.  The proportion of NS C glabrata isolates rose significantly during 2008-2014, and NS C glabrata frequency differed across hospitals. In addition to acquired resistance resulting from prior drug exposure, occurrence of NS C glabrata without prior echinocandin exposure suggests possible transmission of resistant organisms.
authors.affiliation: Epidemic Intelligence Service , Centers for Disease Control and Prevention ; Mycotic Diseases Branch, Division of Foodborne , Waterborne and Environmental Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia.
authors.forename: Snigdha
authors.initials: S
authors.lastname: Vallabhaneni
authors.affiliation: Mycotic Diseases Branch, Division of Foodborne , Waterborne and Environmental Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia.
authors.forename: Angela A
authors.initials: AA
authors.lastname: Cleveland
authors.affiliation: Department of Medicine , Emory University School of Medicine , Atlanta, Georgia ; Atlanta Veterans Affairs Medical Center , Georgia.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Farley
authors.affiliation: Department of International Health , Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Lee H
authors.initials: LH
authors.lastname: Harrison
authors.affiliation: Vanderbilt University School of Medicine , Nashville, Tennessee.
authors.forename: William
authors.initials: W
authors.lastname: Schaffner
authors.affiliation: Acute and Communicable Disease Prevention, Oregon Health Authority , Portland.
authors.forename: Zintar G
authors.initials: ZG
authors.lastname: Beldavs
authors.affiliation: Biostatistics and Information Management Office , Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Derado
authors.affiliation: Mycotic Diseases Branch, Division of Foodborne , Waterborne and Environmental Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia.
authors.forename: Cau D
authors.initials: CD
authors.lastname: Pham
authors.affiliation: Mycotic Diseases Branch, Division of Foodborne , Waterborne and Environmental Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia.
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockhart
authors.affiliation: Mycotic Diseases Branch, Division of Foodborne , Waterborne and Environmental Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Smith
keywords: Candida glabrata; Candidemia; echinocandin resistance; epidemiology; risk factors; transmission of drug resistance