Optimizing Dosing Regimen of Piperacillin/Tazobactam for Nosocomial Pneumonia

1. To observe clinical and bacteriologic responses of different regimens of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) for treatment of nosocomial pneumonia. 2. To describe the pharmacokinetic profile of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) in patients with nosocomial pneumonia. 3. To assess the safety profiles of piperacillin/tazobactam 4.5g q6h, prolonged or intermittent infusion in patients with nosocomial pneumonia.

Enrolled patients will be randomized into therapeutic or controlled group. Controlled group will receive piperacillin/tazobactam of 4.5g Q6h, intermittent infusion for 30 minutes. Therapy group will receive piperacillin/tazobactam of 4.5g Q6h, prolonged infusion for 4 hours. The duration is 7-14 days. Two sets of blood cultures (for aerobic and anaerobic culture) were obtained before the study and post-treatment period if first blood culture is positive. Cultures from the lower respiratory tract infection were obtained before (within 48 h) the study and on the last day of therapy. The lower respiratory tract specimens obtained either by endotracheal aspiration, bronchoalveolar lavage (BAL), a protected brush procedure (PBP) or as sputum were required to show \> 25 polymorphonuclear cells and \< 10 squamous epithelial cells per field (at 100× magnification). The plasma concentration of piperacillin and tazobactam will be determined by LC/MS/MS method. The QC samples will also be analyzed simultaneously with each run for the method stability testing, according to the laboratory standard procedure.