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

: Omadacycline is a potent aminomethylcycline, with activity against Gram-positive, Gram-negative, and anaerobic bacteria. Preliminary data demonstrated that omadacycline has activity against ; however, large-scale studies have not been done. The purpose of this study was to assess the susceptibility of omadacycline and comparators on a large biobank of clinical isolates. 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. Two hundred and fifty clinical isolates collected between 2015 and 2018 were tested for 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 activity with a MIC range of 0.016 to 0.13 ug/mL,a MIC of 0.031 ug/mL, and MIC of 0.031 ug/mL. No difference was observed for omadacycline MIC and MIC 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 phylogeny.: Further development of omadacycline as an intravenous and oral antibiotic directed towards CDI is warranted.