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

Objective. 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. Design. Prospective, open-label study. Setting. An intensive care unit and research ward in a university hospital. Patients. Ten adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation. Interventions. 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. Measurements and main results. The mean+/-SD steady-state plasma trough, peak, and intermediate concentrations were 8.5+/-4.6 mug/ml, 55.9+/-21.6 mug/ml, and 24.0+/-13.8 mug/ml for piperacillin, and 2.1+/-1.0 mug/ml, 4.8+/-2.1 mug/ml, and 2.4+/-1.2 mug/ml for tazobactam, respectively. The mean+/-SD steady-state intermediate ELF concentrations were 13.6+/-9.4 mug/ml for piperacillin and 2.1+/-1.1 mug/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. Conclusion. 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.