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

Abstract

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.

• Authors: Emmanuel Boselli, Dominique Breilh, Thomas Rimmelé, Christian Guillaume, Fabien Xuereb, Marie-Claude Saux, Lionel Bouvet, Dominique Chassard, Bernard Allaouchiche
• Journal: Critical care medicine (Crit Care Med) Vol. 36 Issue 5 Pg. 1500-6 (May 2008) ISSN: 1530-0293 [Electronic] United States
• PMID: 18434883 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Penicillanic Acid
• Tazobactam
• Piperacillin

Topics

• Aged
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics)
• Female
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Penicillanic Acid (administration & dosage, analogs & derivatives, pharmacokinetics)
• Piperacillin (administration & dosage, pharmacokinetics)
• Pneumonia, Ventilator-Associated (metabolism)
• Prospective Studies
• Pulmonary Alveoli (metabolism)
• Tazobactam