Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistant Acinetobacter baumannii

• DOI: 10.3389/fmicb.2022.1013939
• Publication Date: 2022-10-20T14:51:26Z
• Authors: Shixing Zhu; Chu Song; Jiayuan Zhang; Shuo Diao; Tobias M. Heinrichs; Frederico S. Martins; Zhihua Lv; Yuanqi Zhu; Mingming Yu; Sherwin K. B. Sy
• Keywords: Acinetobacter baumannii; Amikacin; Polymyxin B; Sulbactam; Polymyxin; Pharmacodynamics; Colistin

Amikacin and polymyxins as monotherapies are ineffective against multidrug-resistant Acinetobacter baumannii at the clinical dose. When polymyxins, aminoglycosides, sulbactam co-administered, combinations exhibit in vitro synergistic activities. The minimum inhibitory concentration (MIC) mutant prevention (MPC) were determined 11 5 resistant isolates of A. harboring OXA-23, respectively, order to derive fraction time over 24-h wherein free drug was within selection window (fTMSW) that above MPC (fT>MPC) from simulated pharmacokinetic profiles. combination these three antibiotics can confer susceptibility multi-drug reduce opportunity for bacteria develop further resistance. Clinical intravenous dosing regimens amikacin, polymyxin-B, predicted optimize fTMSW fT>MPC exposures blood. Mean ≥ 60% 80% amikacin whereas mean reduced <30% <15%, triple antibiotic combination. Due low polymyxin-B epithelial lining fluid, two pharmacodynamic parameters lung after administration not optimal even therapy setting.