Activity of Omadacycline, a New Tetracycline Analog, and Comparators against Clostridioides difficile.
Khurshida Begum, Eugénie Bassères, Julie Miranda, Chris Lancaster, Anne J Gonzales-Luna, Travis J Carlson, Tasnuva Rashid, David W Eyre, Mark H Wilcox, M Jahangir Alam, Kevin W Garey
Author Information
Khurshida Begum: University of Houston College of Pharmacy, Houston, Texas, USA.
Eugénie Bassères: University of Houston College of Pharmacy, Houston, Texas, USA.
Julie Miranda: University of Houston College of Pharmacy, Houston, Texas, USA.
Chris Lancaster: University of Houston College of Pharmacy, Houston, Texas, USA.
Anne J Gonzales-Luna: University of Houston College of Pharmacy, Houston, Texas, USA.
Travis J Carlson: Fred Wilson School of Pharmacy, High Point University, High Point, North Carolina, USA.
Tasnuva Rashid: University of Houston College of Pharmacy, Houston, Texas, USA.
David W Eyre: Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Mark H Wilcox: Healthcare Associated Infections Research Group, Leeds Institute for Medical Research, University of Leeds, Old Medical School, Leeds General Infirmary, Leeds, United Kingdom.
M Jahangir Alam: University of Houston College of Pharmacy, Houston, Texas, USA.
Kevin W Garey: University of Houston College of Pharmacy, Houston, Texas, USA kgarey@uh.edu. ORCID
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, and vancomycin) was assessed using the broth microdilution method. Minimum bactericidal concentrations (MBCs) and time-kill assays were assessed for pharmacodynamics analysis, and whole-genome sequencing was performed in a subset of isolates to assess distribution of MICs and resistance determinants. Two hundred fifty clinical isolates collected between 2015 and 2018 were tested for susceptibility of omadacycline and comparators. Ribotypes included F001 ( = 5), F002 ( = 56), F014-020 ( = 66), F017 ( = 8), F027 ( = 53), F106 ( = 45), and F255 ( = 17). Omadacycline demonstrated potent activity with an MIC range of 0.016 to 0.13 μg/ml, an MIC of 0.031 μg/ml, and an MIC of 0.031 μg/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 was observed in MIC based on phylogeny. Further development of omadacycline as an intravenous and oral antibiotic directed toward infection is warranted.
