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Hospital outbreak due to Clostridium difficile ribotype 018 (RT018) in Southern Germany
Authors:Fabian K. Berger  Sabine Gfrörer  Sören L. Becker  Rossella Baldan  Daniela Maria Cirillo  Martinique Frentrup  Matthias Steglich  Pit Engling  Ulrich Nübel  Alexander Mellmann  Markus Bischoff  Barbara Gärtner  Lutz von Müller
Affiliation:1. Institute of Medical Microbiology and Hygiene, National Reference Centre for Clostridium difficile, Saarland University, Kirrberger Straße, Building 43, 66421 Homburg, Saar, Germany;2. Regionale Kliniken Holding RKH GmbH, Ludwigsburg, Germany;3. Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland;4. University of Basel, P.O. Box, CH-4003 Basel, Switzerland;5. Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Via Olgettina Milano 60, 20132 Italy;6. Leibniz Institute DSMZ, Inhoffenstraße 7B, 38124 Braunschweig, Germany;7. German Centre for Infection Research (DZIF), Partner site Braunschweig-Hannover, Inhoffenstraße 7, 38124 Braunschweig, Germany;8. Braunschweig Integrated Centre of Systems Biology (BRICS), Technical University Braunschweig, Rebenring 56, 38106 Braunschweig, Germany;9. Institute of Hygiene, University Hospital Münster, National Reference Centre for Clostridium difficile, Robert-Koch-Straße 41, 48149 Münster, Germany;10. Institute for Laboratory Medicine, Microbiology and Hygiene, National Reference Centre for Clostridium difficile, Christophorus Kliniken, Südwall 22, 48653 Coesfeld, Germany
Abstract:
Clostridium (Clostridioides) difficile is the main cause of nosocomial diarrhoea. Ribotype 018 (RT018) has been recognized as the predominant strain responsible for C. difficile infection (CDI) in Italy, whereas in most other European countries only sporadic RT018 cases occur.Between August and October 2015, a suspected C. difficile outbreak at two associated hospitals in Southern Germany was investigated by comprehensive molecular typing. Surprisingly, RT018 was detected in 9/82 CDI patients, which has never been described before in a German outbreak. Phenotypic analysis revealed fluoroquinolone and macrolide resistance. Genetic subtyping using multiple-locus variable-number tandem-repeat analysis (MLVA) and whole genome sequencing (WGS) was performed and outbreak isolates were directly compared to sporadic German RT018 isolates and to epidemic ones from Milan, Northern Italy. Molecular typing confirmed a hospital outbreak with closely related RT018 isolates. Both, MLVA and WGS revealed high similarity of outbreak strains with epidemic isolates from Italy, but low similarity to other German isolates. Comparison between both typing strategies showed that ribotyping in combination with MLVA was appropriate to identify related isolates and clonal complexes, whereas WGS provided a better discrimination with more detailed information about the phylogenetic relationship of isolates. This is the first hospital outbreak in Germany presumably caused by cross-national transmission of an Italian epidemic RT018 strain.
Keywords:Epidemiology  Resistance testing  Transmission  Antibiotic susceptibility
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