In vitro pharmacodynamics of omadacycline against Escherichia coli and Acinetobacter baumannii. (9th December 2020)

• Record Type: Journal Article
• Authors: Noel, A R; Attwood, M; Bowker, K E; MacGowan, A P
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 76:Number 3(2021)
• Page Start: 667
• Page End: 670
• Publication Date: 2020-12-09
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkaa508
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: The pharmacodynamics of omadacycline have been extensively studied against Gram-positive pathogens but less information is available for Gram-negative pathogens. We describe the pre-clinical pharmacodynamics of omadacycline against Escherichia coli and Acinetobacter baumannii. Methods: An in vitro dilutional pharmacokinetic model was used. Exposure experiments with f AUC/MIC ratios ranging from 0 to 1200 were performed using five strains of E. coli and five strains of A. baumannii . Reduction in bacterial load and changes in population profiles were measured. Results: The f AUC/MIC targets against E. coli for 24 h static and −1 log reduction in load were 25.3 ± 17.2 and 42.7 ± 32.5, respectively. For A. baumannii the f AUC/MIC for 24 h static effect was 108.1 ± 38.6. Changes in population profiles were observed for E. coli at f AUC/MIC ratios of ≤200 and for A. baumannii up to 1200. MICs were increased 2–32 fold. Conclusions: f AUC/MIC targets for A. baumannii are greater than for E.coli and changes in population profiles more likely. E. coli f AUC/MIC targets align with in vivo data and will be useful in determining omadacycline dosing for this pathogen.