In vitro Activity of Omadacycline, a New Tetracycline Analog, and Comparators Against Clostridioides difficile.

Background: Omadacycline is a potent aminomethylcycline, with in vitro activity against Gram-positive, Gram-negative, and anaerobic bacteria. Preliminary data demonstrated that omadacycline has in vitro activity against Clostridioides difficile; however, large-scale in vitro studies have not been done. The purpose of this study was to assess the in vitro susceptibility of omadacycline and comparators on a large biobank of clinical C. difficile isolates.Methods:In vitro C. difficile susceptibility to omadacycline and comparators (fidaxomicin, metronidazole, vancomycin) were assessed using the broth microdilution method. Minimum bactericidal concentrations (MBC) and time kill assays were assessed for pharmacodynamics analysis and whole genome sequencing was performed in a subset of isolates to assess distribution of minimum inhibitory concentrations (MICs) and resistance determinants.Results Two hundred and fifty clinical C. difficile isolates collected between 2015 and 2018 were tested for in vitro susceptibility of omadacycline and comparators. Ribotypes included F001 (n=5), F002 (n=56), F014-020 (n=66), F017 (n=8), F027 (n=53), F106 (n=45), and F255 (n=17). Omadacycline demonstrated potent in vitro activity with a MIC range of 0.016 to 0.13 ug/mL,a MIC50 of 0.031 ug/mL, and MIC90 of 0.031 ug/mL. No difference was observed for omadacycline MIC50 and MIC90 values stratified by ribotype, disease severity, or vancomycin susceptibility. Bactericidal activity was confirmed in time kill studies. No difference were observed in MIC based on C. difficile phylogeny.Conclusion: Further development of omadacycline as an intravenous and oral antibiotic directed towards CDI is warranted.