biostudies-literatureMaynard MNIAID NIH HHSHHS | NIH | National Institute of Allergy and Infectious DiseasesHHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)e0185320https://www.ebi.ac.uk/biostudies/studies/S-EPMC8284464biostudies-literatureUnknown65(8)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 <i>bla</i>_KPC-3-harboring Klebsiella pneumoniae in 10-day <i>in vitro</i> 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 higherAntimicrobial agents and chemotherapyPolymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get.PMC8284464R01AI121430R01 AI121430Drusano GLVicchiarelli MDuncanson BLouie ANole JMaynard MBrown DMyrick JLiu WfalsePolymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get.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 <i>bla</i>_KPC-3-harboring Klebsiella pneumoniae in 10-day <i>in vitro</i> 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 higher2021-01-01T00:00:00Z2021 Jul2026-07-16T11:55:14.001Z2026-07-09T10:51:59.741ZS-EPMC82844643409748710.1128/AAC.01853-2010.1128/aac.01853-20