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Clin Pharmacol Ther. 2014 Oct;96(4):438-48. doi: 10.1038/clpt.2014.131. Epub 2014 Jun 13.

Pulmonary penetration of piperacillin and tazobactam in critically ill patients.

Author information

1
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.
2
University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
3
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.
4
Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.

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.

PMID:
24926779
PMCID:
PMC4169708
DOI:
10.1038/clpt.2014.131
[Indexed for MEDLINE]
Free PMC Article

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