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 2 UK regions. From 2-step testing, all glutamate dehydrogenase (GDH)-positive specimens, regardless of fecal toxin result, from Oxford (April 2012 through April 2013) and Leeds (July 2012 through April 2013) 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. A total of 1447 of 12 772 (11%) fecal samples were GDH positive, 866 of 1447 (60%) contained toxigenic C. difficile, and fecal toxin was detected in 511 of 866 (59%), representing 235 Leeds and 191 Oxford TS⁺/FT⁺ cases. TS⁺/FT⁺ cases were 3 times more likely to be plausibly acquired from a previous TS⁺/FT⁺ case than a TS⁺/FT⁺ patient. Fifty-one of 265 (19%) 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 of 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.