Whole-genome sequencing to determine the extent of Clostridium difficile transmission in a high incidence setting in North Wales in 2015

OBJECTIVES: Rates of C. difficile infection (CDI) are higher in North Wales than elsewhere in the UK. We used whole-genome sequencing to investigate if this is due to increased healthcare-associated transmission from other cases. METHODS: Healthcare and community C. difficile isolates from patients across North Wales (February-July-2015) from glutamate dehydrogenase (GDH)-positive faecal samples underwent WGS. Data from patient records, hospital management systems, and national antimicrobial use surveillance were used. RESULTS: 338/499(68%) GDH-positive samples were sequenced, and 299 distinct infections/colonisations identified, 229/299(77%) with toxin genes. Only 39/229(17%) toxigenic isolates were related within ≤2 SNPs to ≥1 infection/colonisation from a previously sampled patient, i.e. demonstrated evidence of possible transmission. Independent predictors of possible transmission included healthcare exposure in the last 12 weeks (p=0.002, with varying rates by hospital), infection with multilocus sequence types ST-1 (ribotype-027) and ST-11 (predominantly ribotype-078) compared to all other toxigenic STs (p<0.001), and cephalosporin exposure in the potential transmission recipient (p=0.02). Adjusting for all these factors, there was no additional effect of ward workload (p=0.54), or failure to meet cleaning targets (p=0.25). Use of antimicrobials is higher in North Wales compared to England and the rest of Wales. CONCLUSIONS: Levels of transmission detected by WGS were comparable to previously described rates in endemic settings; other explanations, such as variations in antimicrobial use, are required to explain the high levels of CDI. Cephalosporins are a risk factor for infection with C. difficile by another infected or colonised case.