title: U.S.-Based National Sentinel Surveillance Study for the Epidemiology of Clostridium difficile-Associated Diarrheal Isolates and Their Susceptibility to Fidaxomicin.
abstract: In 2011 a surveillance study for the susceptibility to fidaxomicin and epidemiology of Clostridium difficile isolates in the United States was undertaken in seven geographically dispersed medical centers. This report encompasses baseline surveillance in 2011 and 2012 on 925 isolates. A convenience sample of C. difficile isolates or toxin positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution (CLSI M11-A8). Clinical and Laboratory Standards Institute (CLSI), Food and Drug Administration, or European Union of Clinical Antimicrobial Susceptibility Testing (EUCAST) breakpoints were applied where applicable. Toxin gene profiles were characterized by multiplex PCR on each isolate. A random sample of 322 strains, stratified by institution, underwent restriction endonuclease analysis (REA). The fidaxomicin MIC90 was 0.5 μg/ml for all isolates regardless of REA type or toxin gene profile, and all isolates were inhibited at ≤1.0 μg/ml. By REA typing, BI strains represented 25.5% of the isolates. The toxin gene profile of tcdA, tcdB, and cdtA/B positive with a tcdC 18-bp deletion correlated with BI REA group. Moxifloxacin and clindamycin resistance was increased among either BI or binary toxin-positive isolates. Metronidazole and vancomycin showed reduced susceptibility (EUCAST criteria) in these isolates. Geographic variations in susceptibility, REA group and binary toxin gene presence were observed. Fidaxomicin activity against C. difficile isolated in a national surveillance study did not change more than 1 year after licensure. This analysis provides baseline results for future comparisons.
authors.affiliation: Tufts Medical Center, Boston, Massachusetts, USA Tufts University School of Medicine, Boston, Massachusetts, USA dsnydman@tuftsmedicalcenter.org.
authors.forename: D R
authors.initials: DR
authors.lastname: Snydman
authors.affiliation: Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: McDermott
authors.affiliation: Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: N V
authors.initials: NV
authors.lastname: Jacobus
authors.affiliation: Tufts Medical Center, Boston, Massachusetts, USA Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: C
authors.initials: C
authors.lastname: Thorpe
authors.affiliation: Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stone
authors.affiliation: Weill Cornell Medical College, New York, New York, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Jenkins
authors.affiliation: R. M. Alden Research Laboratory, Santa Monica, California, USA.
authors.forename: E J C
authors.initials: EJ
authors.lastname: Goldstein
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: R
authors.initials: R
authors.lastname: Patel
authors.affiliation: Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Forbes
authors.affiliation: Duke University Health System, Durham, North Carolina, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mirrett
authors.affiliation: Hines VA Hospital, Hines, Illinois, USA Loyola University Chicago, Maywood, Illinois, USA.
authors.forename: S
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Hines VA Hospital, Hines, Illinois, USA Loyola University Chicago, Maywood, Illinois, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: Gerding
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D002981:Clindamycin / Q000494:pharmacology; D016360:Clostridioides difficile / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D003967:Diarrhea / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D000077732:Fidaxomicin; D024841:Fluoroquinolones / Q000494:pharmacology; D005798:Genes, Bacterial; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D060885:Multiplex Polymerase Chain Reaction; D000091402:Prohibitins; D018571:Sentinel Surveillance; D014481:United States / Q000453:epidemiology; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D024841:Fluoroquinolones; C000717331:PHB2 protein, human; D000091402:Prohibitins; D008795:Metronidazole; D002981:Clindamycin; D014640:Vancomycin; D000077266:Moxifloxacin; D000077732:Fidaxomicin