Polymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get.

ABSTRACT: Dose range studies for polymyxin B (PMB) regimens of 0.75 to 12 mg/kg given every 12 h (q12h) were evaluated for bacterial killing and resistance prevention against an AmpC-overexpressing Pseudomonas aeruginosa and a bla_KPC-3-harboring Klebsiella pneumoniae in 10-day in vitro hollow-fiber models. An exposure-response was observed. But all regimens failed due to regrowth. Lower-dose regimens amplified isolates that expressed transient, lower-level adaptive resistance to PMB (MICs ≤ 4 mg/liter). Higher PMB dosages amplified isolates that expressed this resistance mechanism, a higher-MIC "moderately stable" adaptive resistance, and a higher-MIC stable resistance to PMB. Failure of the highest dose regimens was solely due to subpopulations that expressed the two higher

SUBMITTER: Maynard M 

PROVIDER: S-EPMC8284464 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature