Steady-state plasma and intrapulmonary concentrations of piperacillin/tazobactam 4 g/0.5 g administered to critically ill patients with severe nosocomial pneumonia

• Published in: Intensive care medicine 2004-05, Vol.30 (5), p.976-979
• Main Authors: BOSELLI, Emmanuel, BREILH, Dominique, CANNESSON, Maxime, XUEREB, Fabien, RIMMELE, Thomas, CHASSARD, Dominique, SAUX, Marie-Claude, ALLAOUCHICHE, Bernard
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthesiology; Antibiotics; Biological and medical sciences; Catheters; Chromatography; Creatinine; Cross Infection - blood; Cross Infection - drug therapy; Epithelial Cells - metabolism; Female; Humans; Infections; Intensive care; Intensive care medicine; Intensive Care Units; Lung - metabolism; Male; Medical sciences; Middle Aged; Pathogens; Penicillanic Acid - analogs & derivatives; Penicillanic Acid - blood; Penicillanic Acid - therapeutic use; Pharmacokinetics; Piperacillin - blood; Piperacillin - therapeutic use; Plasma; Pneumonia; Pneumonia, Bacterial - blood; Pneumonia, Bacterial - drug therapy; Pneumonia, Bacterial - etiology; Prospective Studies; Respiration, Artificial - adverse effects; Ventilators
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-004-2222-8

To determine the steady-state plasma and epithelial lining fluid (ELF) concentrations of piperacillin/tazobactam (P/T) administered to critically ill patients with severe bacterial pneumonia. Prospective, open-label study. An intensive care unit and research ward in a university hospital. Ten adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation. All subjects received a 30-min intravenous infusion of P/T 4 g/0.5 g every 8 h. The steady-state plasma and ELF concentrations of P/T were determined by high-performance liquid chromatography. The mean+/-SD steady-state plasma trough, peak, and intermediate concentrations were 8.5+/-4.6 microg/ml, 55.9+/-21.6 microg/ml, and 24.0+/-13.8 microg/ml for piperacillin, and 2.1+/-1.0 microg/ml, 4.8+/-2.1 microg/ml, and 2.4+/-1.2 microg/ml for tazobactam, respectively. The mean+/-SD steady-state intermediate ELF concentrations were 13.6+/-9.4 microg/ml for piperacillin and 2.1+/-1.1 microg/ml for tazobactam, respectively, showing a mean percentage penetration of piperacillin and tazobactam into ELF of 56.8% and 91.3 %, respectively, with a P/T ratio of 6.5:1. Our results show that during the treatment of severe nosocomial pneumonia, a regimen of P/T 4 g/0.5 g every 8 h might provide insufficient concentrations into lung tissue to exceed the MIC of many causative pathogens. This suggests that higher doses of P/T should be administered in order to maximize the antibiotic concentration at the site of infection, or that a second antimicrobial agent should be used in association.