WGS to determine the extent of Clostridioides difficile transmission in a high incidence setting in North Wales in 2015.

Objectives Rates of Clostridioides (Clostridium) difficile infection (CDI) are higher in North Wales than elsewhere in the UK. We used WGS 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 Of the 499 GDH-positive samples, 338 (68%) were sequenced and 299 distinct infections/colonizations were identified, 229/299 (77%) with toxin genes. Only 39/229 (17%) toxigenic isolates were related within 2SNPs to 1 infections/colonizations from a previously sampled patient, i.e. demonstrated evidence of possible transmission. Independent predictors of possible transmission included healthcare exposure in the last 12weeks (P=0.002, with rates varying by hospital), infection with MLST types ST-1 (ribotype 027) and ST-11 (predominantly ribotype 078) compared with 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 with 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 from another infected or colonized case.