Open AccessIn Vitro Activity of Omadacycline, a New Tetracycline Analog, and Comparators against Clostridioides difficile
Author(s) -
Khurshida Begum,
Eugénie Bassères,
Julie Miranda,
Chris Lancaster,
Anne J Gonzales-Luna,
Travis J Carlson,
Tasnuva Rashid,
David W Eyre,
Mark H. Wilcox,
Mohammad Jahangir Alam,
Kevin W. Garey
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00522-20
Subject(s) - in vitro , clostridioides , tetracycline , pharmacology , chemistry , microbiology and biotechnology , medicine , biology , antibiotics , biochemistry
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. In vitro C. difficile 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 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 an MIC range of 0.016 to 0.13 μg/ml, an MIC 50 of 0.031 μg/ml, and an MIC 90 of 0.031 μg/ml. No difference was observed for omadacycline MIC 50 and MIC 90 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 C. difficile phylogeny. Further development of omadacycline as an intravenous and oral antibiotic directed toward C. difficile infection is warranted.