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Alveolar concentrations of piperacillin/tazobactam administered in continuous infusion to patients with ventilator-associated pneumonia.

Author(s): Boselli E, Breilh D, Rimmele T, Guillaume C, Xuereb F, Saux MC, Bouvet L, Chassard D, Allaouchiche B

Affiliation(s): Claude Bernard Lyon I University, Lyon, France. emmanuel.boselli@chu-lyon.fr

Publication date & source: 2008-05, Crit Care Med., 36(5):1500-6.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

OBJECTIVES: To determine the steady-state serum and alveolar concentrations of piperacillin/tazobactam administered in continuous infusion to critically ill patients with ventilator-associated pneumonia and various degrees of renal failure. DESIGN: Prospective comparative study. SETTING: An intensive care unit and research ward in a university hospital. PATIENTS: Forty patients with microbiologically documented ventilator-associated pneumonia. INTERVENTIONS: Patients were randomized to receive piperacillin/tazobactam daily continuous infusions of 12/1.5 g or 16/2 g after a loading dose of 4/0.5 g. The serum and alveolar piperacillin/tazobactam concentrations were determined at steady-state with high performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The median (interquartile) serum and alveolar piperacillin concentrations were respectively 25.3 mg/L (23.1-32.6) and 12.7 mg/L (6.7-18.0) for 12/1.5 g/day, and 38.9 mg/L (32.9-59.6) and 19.1 mg/L (14.0-21.5), respectively, for 16/2 g/day in patients with no/mild renal failure. In patients with moderate/advance renal failure, the median (interquartile) serum and alveolar piperacillin concentrations were 102.4 mg/L (97.4-112.6) and 44.1 mg/L (33.4-48.3), respectively, for 12/1.5 g/day, and 135.3 mg/L (119.5-146.2) and 54.9 mg/L (45.2-110.3), respectively, for 16/2 g/day. Our results show great variability in piperacillin/tazobactam concentrations, with an alveolar percentage penetration of 40-50% for piperacillin and 65-85% for tazobactam and a negative association between serum or alveolar concentrations and creatinine clearance. CONCLUSIONS: A target piperacillin serum concentration of at least 35-40 mg/L is probably required to provide alveolar concentrations exceeding the susceptibility breakpoint for gram-negative bacteria (16 mg/L) during ventilator-associated pneumonia. In patients with no/mild renal failure, a continuous daily dose of piperacillin/tazobactam 16/2 g allows reaching this target concentration, which might be not observed with 12/1.5 g/day. In patients with moderate/advanced renal failure, both dosages achieve serum concentrations far above the 35-40 mg/L threshold, suggesting that in that case, therapeutic drug monitoring should be performed in order to adjust the daily dose.

Page last updated: 2008-06-22

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