Contribution to Clostridium difficile transmission of symptomatic patients with toxigenic strains who are fecal toxin negative

Background The role of symptomatic patients who are toxigenic strain-positive (TS+) but fecal toxin negative (FT-) in transmission of Clostridium difficile is currently unknown. Methods We investigated the contribution of symptomatic TS+/FT- and TS+/FT+ patients in C. difficile transmission in two UK regions. From two-step testing, all glutamate dehydrogenase (GDH)-positive specimens, regardless of fecal toxin result, from Oxford (April2012-April2013) and Leeds (July2012-April2013) microbiology laboratories underwent culture and whole-genome sequencing (WGS), using WGS to identify toxigenic strains. Plausible sources for each TS+/FT+ case, including TS+/FT- and TS+/FT+ patients, were determined using WGS, with and without hospital admission data. Results 1447/12772(11%) fecal samples were GDH-positive, 866/1447(60%) contained toxigenic C. difficile and fecal toxin was detected in 511/866(59%), representing 235 Leeds and 191 Oxford TS+/FT+ cases. TS+/FT+ cases were three times more likely to be plausibly acquired from a previous TS+/FT+ case than a TS+/FT- patient. 51(19%) of 265 TS+/FT+ cases diagnosed >3 months into the study were genetically-related (≤2 single nucleotide polymorphisms) to ≥1 previous TS+/FT+ case or TS+/FT- patient: 27(10%) to only TS+/FT+ cases, 9(3%) to only TS+/FT- patients, and 15(6%) to both. Only 10/265(4%) were genetically-related to a previous TS+/FT+ or TS+/FT- patient and shared the same ward simultaneously or within 28 days. Conclusions Symptomatic TS+/FT- patients were a source of C. difficile transmission, although they accounted for less onward transmission than TS+/FT+ cases. Although transmission from symptomatic patients with either fecal toxin status accounted for a low overall proportion of new cases, both groups should be infection control targets.