Contribution to Clostridium Difficile Transmission of Symptomatic Patients With Toxigenic Strains Who Are Fecal Toxin Negative

“…Our findings also support the recently reported role in transmission of GDH-positive patients with toxigenic C. difficile , but no detected fecal-toxin [ 28 ]. By sequencing all GDH-positive cases, we were able to compare the probability of fecal-toxin-positive and toxin-negative patients being potential sources of transmission, that is, having C. difficile genetically linked to a subsequent C. difficile isolate in another patient.…”

“…However, the proportion of cases linked to a previous case varied between 11% and 27% at the three main hospitals suggesting potential for reductions in overall incidence. Supporting the previously described role in transmission of GDH-positive patients without detectable faecal toxin, 26 7/39 (18%) of toxigenic C. difficile acquisitions could only be linked to consistently toxin-negative sources. Therefore, all patients with toxigenic C. difficile should be a focus of infection control efforts, not just those with detectable faecal toxin.…”

“…Thus, our data support the position that existing C. difficile clonality definitions (Յ2 core genome SNVs), based on estimates of within-host genetic diversity from measurements of C. difficile microevolution in adults with CDI relapses (2), will be minimally biased from random selection of a single colony from stool culture for WGS. With recent studies suggesting that WGS is the optimal method for identifying putative transmission events with exquisite sensitivity (2)(3)(4), our data suggest that using WGS of single colonies to identify putative C. difficile transmission events will appropriately characterize the vast majority of events using existing clonality definitions. A strength of this study is the use of rigorous bioinformatics analyses adapted from methods described by Eyre et al (2) and that we have previously applied to investigation of C. difficile transmission in children (4), Our study is limited by a relatively small sample size, and this prevents an extensive assessment for the host and pathogen factors that contribute to rare cases of within-host diversity.…”