{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Maynard M"],"funding":["NIAID NIH HHS","HHS | NIH | National Institute of Allergy and Infectious Diseases","HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)"],"pagination":["e0185320"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8284464"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["65(8)"],"pubmed_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 <i>bla</i><sub>KPC-3</sub>-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 higher"],"journal":["Antimicrobial agents and chemotherapy"],"pubmed_title":["Polymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get."],"pmcid":["PMC8284464"],"funding_grant_id":["R01AI121430","R01 AI121430"],"pubmed_authors":["Drusano GL","Vicchiarelli M","Duncanson B","Louie A","Nole J","Maynard M","Brown D","Myrick J","Liu W"],"additional_accession":[]},"is_claimable":false,"name":"Polymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get.","description":"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><sub>KPC-3</sub>-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 higher","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jul","modification":"2026-07-16T11:55:14.001Z","creation":"2026-07-09T10:51:59.741Z"},"accession":"S-EPMC8284464","cross_references":{"pubmed":["34097487"],"doi":["10.1128/AAC.01853-20","10.1128/aac.01853-20"]}}