title: Pulmonary penetration of piperacillin and tazobactam in critically ill patients.
abstract: Pulmonary infections in critically ill patients are common and are associated with high morbidity and mortality. Piperacillin-tazobactam is a frequently used therapy in critically ill patients with pulmonary infection. Antibiotic concentrations in the lung reflect target-site antibiotic concentrations in patients with pneumonia. The aim of this study was to assess the plasma and intrapulmonary pharmacokinetics (PK) of piperacillin-tazobactam in critically ill patients administered standard piperacillin-tazobactam regimens. A population PK model was developed to describe plasma and intrapulmonary piperacillin and tazobactam concentrations. The probability of piperacillin exposures reaching pharmacodynamic end points and the impact of pulmonary permeability on piperacillin and tazobactam pulmonary penetration was explored. The median piperacillin and tazobactam pulmonary penetration ratios were 49.3 and 121.2%, respectively. Pulmonary piperacillin and tazobactam concentrations were unpredictable and negatively correlated with pulmonary permeability. Current piperacillin-tazobactam regimens may be insufficient to treat pneumonia caused by piperacillin-tazobactam-susceptible organisms in some critically ill patients.
authors.affiliation: 1] NIHR Translational Research Facility in Respiratory Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK [2] University Hospital of South Manchester NHS Foundation Trust, Manchester, UK [3] Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: T W
authors.initials: TW
authors.lastname: Felton
authors.affiliation: University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: K
authors.initials: K
authors.lastname: McCalman
authors.affiliation: 1] NIHR Translational Research Facility in Respiratory Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK [2] University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: I
authors.initials: I
authors.lastname: Malagon
authors.affiliation: University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: B
authors.initials: B
authors.lastname: Isalska
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: S
authors.initials: S
authors.lastname: Whalley
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: J
authors.initials: J
authors.lastname: Goodwin
authors.affiliation: 1] NIHR Translational Research Facility in Respiratory Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK [2] University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Bentley
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: W W
authors.initials: WW
authors.lastname: Hope
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D016638:Critical Illness; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010539:Permeability; D010878:Piperacillin / Q000097:blood / Q000493:pharmacokinetics*; D000078142:Tazobactam
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin