Impact of Oral Metronidazole, Vancomycin, and Fidaxomicin on Host Shedding and Environmental Contamination with Clostridioides difficile.

OBJECTIVES Shedding of Clostridioides difficile spores from infected individuals contaminates the hospital environment and contributes to infection transmission. We assessed whether antibiotic selection impacts C. difficile shedding and contamination of the hospital environment. METHODS In this prospective, unblinded, randomized controlled trial of hospitalized adults with C. difficile infection, subjects were randomized 1:1:1 to receive fidaxomicin, oral vancomycin, or metronidazole. The primary outcome was change in environmental contamination rate while on treatment. Secondary outcomes included stool shedding, total burden of contamination, and molecular relatedness of stool versus environmental C. difficile isolates. RESULTS 33 patients were enrolled and 31 (94%) completed the study. Fidaxomicin (-0.36 log10 CFU/day, 95% CI -0.52 to -0.19, p<0.01) and vancomycin (-0.17 log10 CFU/day, 95% CI -0.34 to -0.01, p=0.05) were associated with more rapid decline in C. difficile shedding compared to metronidazole (-0.01 log10 CFU/day, 95% CI -0.10 to +0.08). Both vancomycin (6.3%, 95% CI 4.7-8.3%) and fidaxomicin (13.1%, 95% CI 10.7-15.9%) were associated with lower rates of environmental contamination than metronidazole (21.4%, 95% CI 18.0-25.2%). When specifically modeling within-subject change over time, fidaxomicin (aOR 0.83, 95% CI 0.70-0.99, p=0.04) was associated with more rapid decline in environmental contamination than vancomycin or metronidazole. Overall, 207 of 233 (88.8%) of environmental C. difficile isolates matched subject stool isolates by ribotyping, without significant difference by treatment. CONCLUSIONS Fidaxomicin, and to a lesser extent vancomycin, reduces C. difficile shedding and contamination of the hospital environment relative to metronidazole. Treatment choice may play a role in reducing healthcare-associated C. difficile transmission.