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Abstract
To trace the routes and frequencies of transmission of Clostridioides difficile in a tertiary-care hospital in Madrid (Spain), we sequenced the genomes from all C. difficile isolates collected over 36 months (2014–2016) that were indistinguishable from any other isolate by PCR ribotyping. From a total of 589 C. difficile infection cases, we cultivated and PCR-ribotyped 367 C. difficile isolates (62%), of which 265 were genome-sequenced. Based on close relatedness of successively collected isolates (≤2 SNPs difference in their genomes), whole-genome sequencing revealed a total of 17 independent, putative transmission clusters, caused by various C. difficile strains and each containing 2 to 18 cases, none of which had been detected previously by standard epidemiological surveillance. Proportions of linked isolates varied widely among PCR ribotypes, from 3% (1/36) for ribotype 014/020 to 60% (12/20) for ribotype 027, suggesting differential aptitudes for nosocomial spread. Remarkably, only a minority (17%) of transmission recipients had direct ward contact to their presumed donors and specific C. difficile genome types frequently went undetectable for several months before re-emerging later, suggesting reservoirs for the pathogen outside of symptomatic patients. Taken together, our analysis based on genome sequencing suggested considerable within-hospital epidemic spread of C. difficile, even though epidemiological data initially had been inconspicuous.
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1 Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Servicio de Microbiología, Madrid, Spain (GRID:grid.411347.4) (ISNI:0000 0000 9248 5770); Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain (GRID:grid.454898.c)
2 Leibniz Institute DSMZ, Braunschweig, Germany (GRID:grid.420081.f) (ISNI:0000 0000 9247 8466)
3 Leibniz Institute DSMZ, Braunschweig, Germany (GRID:grid.420081.f) (ISNI:0000 0000 9247 8466); German Center of Infection Research (DZIF), Braunschweig, Germany (GRID:grid.452463.2)
4 Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Servicio de Microbiología, Madrid, Spain (GRID:grid.411347.4) (ISNI:0000 0000 9248 5770)
5 Hospital Universitario Ramón y Cajal, Servicio de Medicina Preventiva, Madrid, Spain (GRID:grid.411347.4) (ISNI:0000 0000 9248 5770)
6 Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain (GRID:grid.454898.c); and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Servicio de Enfermedades Infecciosas, Madrid, Spain (GRID:grid.420232.5)
7 Leibniz Institute DSMZ, Braunschweig, Germany (GRID:grid.420081.f) (ISNI:0000 0000 9247 8466); German Center of Infection Research (DZIF), Braunschweig, Germany (GRID:grid.452463.2); Technical University, Braunschweig Integrated Center of Systems Biology (BRICS), Braunschweig, Germany (GRID:grid.6738.a) (ISNI:0000 0001 1090 0254)