Methods: During a Phase 2b, clinical study with ribaxamase which demonstrated a significant reduction in Clostridium difficile infection in patients receiving ceftriaxone + ribaxamase, longitudinal fecal samples were collected from the patients. DNA extracted from these samples was 16S rRNA and whole genome sequenced, and the sequences were analyzed for changes in the gut microbiome and resistome. Statistical analyses were performed to determine correlations between changes in the gut microbiome and resistome and clinical study data.
Results: Sequence analyses revealed that ribaxamase protected the integrity of the gut microbiome, including preventing enterococcal mono-domination (defined as >30% of the microbiome being from one genus), and identified over 1300 AMR genes in the gut resistome. LefSe analysis of the gut resistome identified a family of β-lactamases (CfxA) and vancomycin resistance genes which demonstrated a significant increase in placebo-treated vs. ribaxamase-treated patients from pre-to post-antibiotics. Analysis by qPCR supported both new acquisition of these genes and expansion of existing AMR pools. Further statistical analyses demonstrated significant correlations between changes in the gut resistome and clinical study parameters including β-lactamase gene frequency and study drug assignment, and efflux pump gene frequency and vancomycin resistance.
Conclusion: Taken together, these findings demonstrated that coadministration of ribaxamase with IV β-lactam antibiotics can protect the integrity of the gut microbiome and may help limit the emergence of AMR induced by these antibiotics.
Synthetic Biologics, Inc.:
K. Trout, Synthetic Biologics, Inc.: Employee , Salary .
J. Cope, None
J. Sliman, Synthetic Biologics, Inc.: Employee , Salary .