title: Pan-European longitudinal surveillance of antibiotic resistance among prevalent Clostridium difficile ribotypes.
abstract: Clostridium difficile infection remains a major healthcare burden. Until the recent introduction of fidaxomicin, antimicrobial treatments were limited to metronidazole and vancomycin. The emergence of epidemic C. difficile PCR ribotype 027 and its potential link to decreased antibiotic susceptibility highlight the lack of large-scale antimicrobial susceptibility and epidemiological data available. We report results of epidemiological and antimicrobial susceptibility investigations of C. difficile isolates collected prior to fidaxomicin introduction, establishing important baseline data. Thirty-nine sites in 22 countries submitted a total of 953 C. difficile isolates for PCR ribotyping, toxin testing, and susceptibility testing to metronidazole, vancomycin, fidaxomicin, rifampicin, moxifloxacin, clindamycin, imipenem, chloramphenicol, and tigecycline. Ninety-nine known ribotypes were identified. Ribotypes 027, 014, 001/072, and 078 were most frequently isolated in line with previous European studies. There was no evidence of resistance to fidaxomicin, and reduced susceptibility to metronidazole and vancomycin was also scarce. Rifampicin, moxifloxacin, and clindamycin resistance (13%, 40%, and 50% of total isolates, respectively) were evident in multiple ribotypes. There was a significant correlation between lack of ribotype diversity and greater antimicrobial resistance (measured by cumulative resistance score). Well-known epidemic ribotypes 027 and 001/072 were associated with multiple antimicrobial resistance, but high levels of resistance were also observed, particularly in 018 and closely related emergent ribotype 356 in Italy. This raises the possibility of antimicrobial exposure as the underlying reason for their appearance, and highlights the need for ongoing epidemiological and antimicrobial resistance surveillance.
authors.affiliation: Microbiology, Leeds Teaching Hospitals Trust, Leeds, West Yorkshire, UK. Electronic address: jane.freeman4@nhs.net.
authors.forename: J
authors.initials: J
authors.lastname: Freeman
authors.affiliation: Healthcare Associated Infections Research Group, Section of Molecular Gastroenterology, Leeds Institute for Biomedical and Clinical Sciences, University of Leeds, Leeds, West Yorkshire, UK.
authors.forename: J
authors.initials: J
authors.lastname: Vernon
authors.affiliation: Microbiology, Leeds Teaching Hospitals Trust, Leeds, West Yorkshire, UK.
authors.forename: K
authors.initials: K
authors.lastname: Morris
authors.affiliation: Healthcare Associated Infections Research Group, Section of Molecular Gastroenterology, Leeds Institute for Biomedical and Clinical Sciences, University of Leeds, Leeds, West Yorkshire, UK.
authors.forename: S
authors.initials: S
authors.lastname: Nicholson
authors.affiliation: Healthcare Associated Infections Research Group, Section of Molecular Gastroenterology, Leeds Institute for Biomedical and Clinical Sciences, University of Leeds, Leeds, West Yorkshire, UK.
authors.forename: S
authors.initials: S
authors.lastname: Todhunter
authors.affiliation: Microbiology, Astellas Pharma Europe Ltd, Chertsey, UK.
authors.forename: C
authors.initials: C
authors.lastname: Longshaw
authors.affiliation: Microbiology, Leeds Teaching Hospitals Trust, Leeds, West Yorkshire, UK; Healthcare Associated Infections Research Group, Section of Molecular Gastroenterology, Leeds Institute for Biomedical and Clinical Sciences, University of Leeds, Leeds, West Yorkshire, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Wilcox
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016360:Clostridioides difficile / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D024881:Drug Resistance, Bacterial; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology*; D005060:Europe / Q000453:epidemiology; D005843:Geography; D006801:Humans; D008137:Longitudinal Studies; D016133:Polymerase Chain Reaction / Q000379:methods; D011159:Population Surveillance; D015995:Prevalence; D021521:Ribotyping
chemical_list: D000900:Anti-Bacterial Agents
keywords: Antimicrobial resistance; Clostridium difficile; PCR ribotyping; epidemiology; surveillance