A Randomized Phase 1 Study Investigating Gut Microbiome Changes With Moxifloxacin vs Oral Vancomycin: Implications for Clostridioides difficile Risk

Background The epidemic Clostridioides difficile ribotype 027 (RT 027) strain is associated with bacterial virulence traits, including faster germination time and resistance to moxifloxacin, a second-generation fluoroquinolone. Although fluoroquinolones are linked to the RT 027 epidemic, studies to understand moxifloxacin as a high-risk antibiotic for C difficile infection (CDI) are limited. This study assessed the microbial taxonomic profile and metabolomic changes in healthy volunteers given moxifloxacin or oral vancomycin, an antibiotic known to increase CDI risk via gut perturbation. Methods This phase 1, nonblinded, randomized clinical trial comprised healthy volunteers aged 18 to 40 years who received moxifloxacin or vancomycin for 10 days. Stool samples were collected at baseline and 12 follow-up visits. Metataxonomics was completed by 16S rRNA sequencing and bile acid metabolites by liquid chromatography–tandem mass spectrometry. Results Moxifloxacin therapy caused minimal microbial disruption, although changes were observed in bacterial species from the Clostridiales order during therapy. Secondary bile acid concentrations decreased from day 0 to day 7 with moxifloxacin therapy. Vancomycin caused more significant changes in the microbiome, including increased Proteobacteria, decreased Clostridiales abundance, and a longer duration of decreased secondary bile acids. Conclusions Moxifloxacin use was associated with specific microbiome and metabolomic changes, increasing CDI risk albeit for a shorter period than vancomycin. This window of vulnerability may help to explain the risk of fluoroquinolones with the faster germination time for RT 027 strains. Clinical Trials Registration.