title: Targeted benefits of prolonged-infusion piperacillin-tazobactam in an in vitro infection model of Pseudomonas aeruginosa.
abstract: Given the inconsistent clinical findings, our goal was to characterize the pharmacodynamics (PDs) of prolonged-infusion piperacillin-tazobactam (TZP) in an in vitro pharmacodynamic model of Pseudomonas aeruginosa. Specifically, the study was designed to investigate the influence of MIC on the activity of prolonged-infusion TZP using pharmacokinetics (PKs) consistent with a non-critically ill patient population. There was no benefit with prolonged- compared with standard-infusion TZP against isolates with susceptible MICs of 8 or 16 mg/L. However, prolonged-infusion TZP produced more than two times the final bacterial kill against less susceptible isolates with an intermediate MIC of 32 mg/L. The PDs of TZP were well described by a sigmoid Emax model (r(2) = 0.84) where %ƒT>MIC thresholds of 27 and 75% were associated with bacteriostatic and bactericidal effects, respectively. However, the well-established PD relationship with %ƒT>MIC was not observed with prolonged-infusion TZP. In conclusion, this study characterizes the targeted benefits of prolong-infusion TZP based on pathogen MIC, and supports the assertion that the benefits are selective and most likely observed in patients with less susceptible pathogens or altered PKs.
authors.affiliation: a Faculty of Health Science, College of Pharmacy , University of Manitoba , Winnipeg , Canada.|b St. Boniface Hospital , Winnipeg , Canada.
authors.forename: S
authors.initials: S
authors.lastname: Zelenitsky
authors.affiliation: a Faculty of Health Science, College of Pharmacy , University of Manitoba , Winnipeg , Canada.
authors.forename: J
authors.initials: J
authors.lastname: Nash
authors.affiliation: a Faculty of Health Science, College of Pharmacy , University of Manitoba , Winnipeg , Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Weber
authors.affiliation: a Faculty of Health Science, College of Pharmacy , University of Manitoba , Winnipeg , Canada.|b St. Boniface Hospital , Winnipeg , Canada.
authors.forename: H
authors.initials: H
authors.lastname: Iacovides
authors.affiliation: a Faculty of Health Science, College of Pharmacy , University of Manitoba , Winnipeg , Canada.|b St. Boniface Hospital , Winnipeg , Canada.
authors.forename: R
authors.initials: R
authors.lastname: Ariano
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin
keywords: Extended-infusion; Pharmacodynamics; Pharmacokinetics; Piperacillin-tazobactam; Prolonged-infusion; Pseudomonas aeruginosa