title: Tracing the Spread of Clostridium difficile Ribotype 027 in Germany Based on Bacterial Genome Sequences.
abstract: We applied whole-genome sequencing to reconstruct the spatial and temporal dynamics underpinning the expansion of Clostridium difficile ribotype 027 in Germany. Based on re-sequencing of genomes from 57 clinical C. difficile isolates, which had been collected from hospitalized patients at 36 locations throughout Germany between 1990 and 2012, we demonstrate that C. difficile genomes have accumulated sequence variation sufficiently fast to document the pathogen's spread at a regional scale. We detected both previously described lineages of fluoroquinolone-resistant C. difficile ribotype 027, FQR1 and FQR2. Using Bayesian phylogeographic analyses, we show that fluoroquinolone-resistant C. difficile 027 was imported into Germany at least four times, that it had been widely disseminated across multiple federal states even before the first outbreak was noted in 2007, and that it has continued to spread since.
authors.affiliation: Robert Koch Institute, Department of Infectious Diseases, Division of Nosocomial Pathogens and Antibiotic Resistances, Wernigerode, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Steglich
authors.affiliation: Robert Koch Institute, Centre for Biological Threats and Special Pathogens, ZBS 1 Highly Pathogenic Viruses, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Nitsche
authors.affiliation: University of Saarland Medical Centre, Institute of Medical Microbiology and Hygiene, National Consultant Laboratory for Clostridium difficile, Homburg, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: von Müller
authors.affiliation: University of Saarland Medical Centre, Institute of Medical Microbiology and Hygiene, National Consultant Laboratory for Clostridium difficile, Homburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Research Center Borstel, Molecular Mycobacteriology, Borstel, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kohl
authors.affiliation: Research Center Borstel, Molecular Mycobacteriology, Borstel, Germany; German Center for Infection Research (DZIF), Partner Site Borstel, Borstel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.affiliation: Leibniz Institute DSMZ, Department of Microbial Genome Research, Braunschweig, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Nübel
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics; D001499:Bayes Theorem; D016360:Clostridioides difficile / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification*; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000382:microbiology; D024841:Fluoroquinolones / Q000627:therapeutic use; D014644:Genetic Variation / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D005858:Germany; D006760:Hospitalization; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D058974:Phylogeography / Q000379:methods; D021521:Ribotyping / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones