Alveolar concentrations of pipeyacillin/tazobactam administered in continuous infusion to patients with ventilatoy-associated pneumonia

作者：Boselli Emmanuel^*; Breilh Dominique; Rimmele Thomas; Guillaume Christian; Xuereb Fabien; Saux Marie Claude; Bouvet Lionel; Chassard Dominique; Allaouchiche Bernard

来源：Critical Care Medicine, 2008, 36(5): 1500-1506.

DOI：10.1097/CCM.0b013618170ba21

• piperacillin/tazobactam
• continuous infusion
• ventilator-associated pneumonia
• pharmacokinetics
• pharmacodynamics
• epithelial lining fluid

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.

• 出版日期2008-5
• 单位河南工业大学