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Pulmonary infections in critically ill patients are common and 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 intra-pulmonary pharmacokinetics (PK) of piperacillin-tazobactam in critically ill patients administered standard piperacillin-tazobactam regimens. A population PK model was developed to describe plasma and intra-pulmonary piperacillin and tazobactam concentrations. The probability of piperacillin exposures reaching pharmacodynamic endpoints and the impact of pulmonary permeability on piperacillin and tazobactam pulmonary penetration was explored.

The median piperacillin and tazobactam pulmonary penetration ratio was 49.3% and 121.2%, respectively. Pulmonary piperacillin and tazobactam concentration were unpredictable and negatively correlated to pulmonary permeability.

Current piperacillin-tazobactam regimens may be insufficient to treat pneumonia caused by piperacillin-tazobactam susceptible organisms in some critically ill patients.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 13 June 2014; doi:10.1038/clpt.2014.131.