In Vitro Pharmacodynamics Of Omadacycline Against Escherichia Coli And Acinetobacter Baumannii

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 fAUC/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 fAUC/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 fAUC/MIC for 24 h static effect was 108.1 +/- 38.6. Changes in population profiles were observed for E. coli at fAUC/MIC ratios of <= 200 and for A. baumannii up to 1200. MICs were increased 2-32 fold.Conclusions: fAUC/MIC targets for A. baumannii are greater than for E.coli and changes in population profiles more Likely. E. coli fAUC/MIC targets align with in vivo data and will be useful in determining omadacycline dosing for this pathogen.