Genomic Determination of Relative Risks for Clostridioides Difficile Infection From Asymptomatic Carriage in Intensive Care Unit Patients

Background: Clostridioides difficile infections (CDIs) are among the most prevalent hospital-associated infections (HAIs), particularly for intensive care unit (ICU) patients. The risks for developing active CDI from asymptomatic carriage of C. difficile are not well understood.

Methods: We identified asymptomatic C. difficile carriage among 1897 ICU patients using rectal swabs from an existing ICU vancomycin-resistant enterococci (VRE) surveillance program. C. difficile isolates from VRE swabs, and from C. difficile-positive stool samples, were genome sequenced. Spatial-temporal data from hospital records assessed genomically identified clusters for potential transmission events.

Results: Genomic analyses identified a diverse set of strains in infected patients and asymptomatic carriers. A total of 7.4% of ICU patients asymptomatically carried C. difficile; 69% of isolates carried an intact toxin locus. In contrast, 96% of C. difficile stool isolates were toxin encoding. CDI rates in asymptomatic carriers of toxin-encoding strains were 5.3% versus 0.57% in noncarriers. The relative risk for CDI with asymptomatic carriage of a toxin-encoding strain was 9.32 (95% confidence interval, 3.25-26.7). Genomic identification of clonal clusters supported analyses for asymptomatic transmission events, with spatial-temporal overlaps identified in 13 of 28 cases.

Conclusions: Our studies provide the first genomically confirmed assessments of CDI relative risk from asymptomatic carriage of toxin-encoding strains and highlight the complex dynamics of asymptomatic transmission in ICUs. Asymptomatic carriers are an active reservoir of C. difficile in the nosocomial environment. C. difficile screening can be implemented within existing HAI surveillance programs and has the potential to support infection-control efforts against this pathogen.