The enemy within

There are a couple studies out this month, one in CID (from WashU) and one in ICHE (from Houston), that carry the same message: a substantial portion (13-15%) of asymptomatic hospitalized adults carry toxigenic strains of Clostridium difficile in their GI tracts. Coming on the heels of this NEJM study using whole-genome sequencing to describe the genetic diversity of C. difficile strains, these studies advance an evolving narrative—that many cases of C. difficile-associated disease (CDAD) are not attributable to in-hospital transmission from other symptomatic patients (and thus are impervious to transmission-prevention approaches such as hand hygiene, contact precautions, and enhanced environmental disinfection). The major take-away point for me: it's all about the stewardship! Knowing that 15% of patients harbor toxigenic C. difficile should only increase the urgency of antimicrobial stewardship efforts.

The other major implication of these studies relates to the predictive value of highly sensitive PCR tests that target the toxin gene(s). To quote from the authors conclusion in Koo, et al:

“In the healthcare setting, where the majority of diarrhea cases are not attributable to CDAD and the prevalence of asymptomatic C. difficile colonization is greater than the frequency of CDAD, NAAT detection of asymptomatic colonization among healthcare-associated diarrhea patients may be contributing to a significant number of CDAD false positives.”

The UK have already changed their surveillance recommendations to require a toxin ELISA as confirmation of every positive PCR test. With lab-identified C. difficile now publicly reportable, I suspect more US centers will switch to two-step algorithms and/or begin restricting access to PCR-based assays to reduce the false positivity problems.

Enhanced scanning EM of C. difficile from the CDC's Public Health Image Library