Natural History of Clostridioides difficile Colonization and Infection Following New Acquisition of Carriage in Healthcare Settings: A Prospective Cohort Study

Abstract Background Limited information is available on the natural history of Clostridioides difficile colonization and infection in patients with new acquisition of C. difficile in healthcare settings. Methods In 3 hospitals and affiliated long-term care facilities, we collected serial perirectal cultures from patients with no diarrhea on enrollment to identify new acquisition of toxigenic C. difficile carriage and determined the duration and burden of carriage. Asymptomatic carriage was defined as transient if only 1 culture was positive, with negative cultures before and after, or persistent if 2 or more cultures were positive. Clearance of carriage was defined as 2 consecutive negative perirectal cultures. Results Of 1432 patients with negative initial cultures and at least 1 follow-up culture, 39 (2.7%) developed C. difficile infection (CDI) without prior detection of carriage and 142 (9.9%) acquired asymptomatic carriage, with 19 (13.4%) subsequently diagnosed with CDI. Of 82 patients analyzed for persistence of carriage, 50 (61.0%) had transient carriage and 32 (39.0%) had persistent carriage, with an estimated median of 77 days to clearance of colonization (range, 14–133 days). Most persistent carriers had a relatively high burden of carriage and maintained the same ribotype over time, whereas most transient carriers had a low burden of carriage detected only using broth enrichment cultures. Conclusions In 3 healthcare facilities, 9.9% of patients acquired asymptomatic carriage of toxigenic C. difficile, and 13.4% were subsequently diagnosed with CDI. Most carriers had transient rather than persistent carriage and most patients developing CDI did not have prior detection of carriage. In 3 healthcare facilities, 9.9% of patients acquired asymptomatic carriage of toxigenic Clostridioides difficile, and 13.4% were subsequently diagnosed with CDI. Most carriers had transient rather than persistent carriage. Most patients developing CDI did not have prior detection of carriage.