A Randomized Phase 1 Study Investigating Gut Microbiome Changes With Moxifloxacin vs Oral Vancomycin: Implications...

Area of Science:

• Microbiome research
• Metabolomics
• Antibiotic effects on gut microbiota

Background:

• The epidemic Clostridioides difficile ribotype 027 (RT 027) strain exhibits enhanced virulence, including rapid germination and fluoroquinolone resistance.
• While fluoroquinolones are implicated in the RT 027 epidemic, the specific risk posed by moxifloxacin for C. difficile infection (CDI) requires further investigation.
• This study investigates the impact of moxifloxacin versus vancomycin on the gut microbiome and metabolome in healthy individuals.

Purpose of the Study:

• To assess the effects of moxifloxacin and vancomycin on the microbial taxonomic profile in healthy volunteers.
• To evaluate the metabolomic changes, specifically bile acid profiles, induced by moxifloxacin and vancomycin.
• To understand the potential mechanisms by which these antibiotics may influence the risk of C. difficile infection.

Main Methods:

• A phase 1, nonblinded, randomized clinical trial involving healthy volunteers aged 18-40 years.
• Participants received either moxifloxacin or vancomycin orally for 10 days.
• Stool samples were analyzed using 16S rRNA sequencing for metataxonomics and liquid chromatography-tandem mass spectrometry for bile acid metabolites.

Main Results:

• Moxifloxacin caused limited microbial disruption, with transient changes in Clostridiales species and a decrease in secondary bile acids from day 0 to day 7.
• Vancomycin induced more substantial microbiome alterations, including an increase in Proteobacteria, a decrease in Clostridiales abundance, and prolonged reduction in secondary bile acids.
• The duration and extent of gut perturbation differed significantly between the two antibiotics.

Conclusions:

• Moxifloxacin use is associated with distinct, albeit shorter-lived, microbiome and metabolomic shifts that may increase CDI risk.
• These findings suggest a potential window of vulnerability explaining the association between fluoroquinolones and RT 027 strains with rapid germination.
• The differential impact of moxifloxacin and vancomycin on the gut environment highlights varying risks for CDI development.