A R Noel1, M Attwood1, K E Bowker1, A P MacGowan1. 1. Bristol Centre for Antimicrobial Research and Evaluation (BCARE), Infection Sciences, Severn Pathology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK.
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 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.
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.
Authors: Taylor Morrisette; Sara Alosaimy; Abdalhamid M Lagnf; Jeremy J Frens; Andrew J Webb; Michael P Veve; Ryan Stevens; Jeannette Bouchard; Tristan W Gore; Iman Ansari; Michael J Rybak Journal: Infect Dis Ther Date: 2022-05-14