489. Bile Acid Concentrations in Healthy Volunteers Receiving Oral Omadacycline or Vancomycin

Abstract

Abstract Background Microbiome disruption associated with Clostridioides difficile infection (CDI) includes reduced metabolism of primary to secondary bile acids leading to increased likelihood of C. difficile germination and CDI recurrence. Omadacycline has potent in vitro activity against C. difficile but its effect on the microbiome is unknown. The purpose of this study was to assess changes in bile acid concentrations in healthy volunteers given omadacycline compared to vancomycin, the most common antibiotic used to treat CDI. Methods As part of an ongoing healthy volunteer study of adults between 18 and 40 years, subjects received a 10-day course of oral omadacycline or vancomycin. Stool samples were collected and bile acids were extracted and quantified via targeted liquid chromatography-mass spectrometry (LC-MS). For this analysis, samples collected at the end of antibiotic therapy (day 9-10) were analyzed for primary and secondary bile acids. Results were compared and visualized using R (ggplot2). Results Between October 2020 and December 2021, 16 healthy volunteers aged 26 ± 5 years (male: 69%; Caucasian: 31%; mean body mass index: 23.6 ± 3.8 kg/m2) were enrolled. Concentrations of primary bile acids (cholic acid and chenodeoxycholic acid) were higher in patients receiving oral vancomycin than those receiving omadacycline (Table 1). Secondary bile acids were higher in the omadacycline arm compared to vancomycin. Secondary:primary bile ratio was higher for omadacycline (0.43) than vancomycin (0.03). Conclusion Omadacycline preserved bile acid homeostasis in the gut to a higher extent that vancomycin, suggesting reduced microbiome dysbiosis. With potent in vitro C. difficile activity, availability as an oral and IV formulations, and favorable microbiome properties, further development of omadacycline for the treatment of CDI is warranted. Disclosures Kevin W. Garey, PharmD, MS, Acurx Pharmaceuticals: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support|Summit Pharmaceuticals: Grant/Research Support.