Piperacillin-tazobactam for Pseudomonas aeruginosa infection:: Clinical implications of an extended-infusion dosing strategy

Background. Piperacillin- tazobactam is frequently used to treat Pseudomonas aeruginosa infections in critically ill patients. In an effort to improve clinical outcomes, an extended- infusion dosing scheme for piperacillintazobactam therapy was devised using a Monte Carlo simulation and was adopted into clinical practice at Albany Medical Center ( Albany, New York). This study evaluates the clinical implications of extended infusion of piperacillintazobactam therapy for critically ill patients with P. aeruginosa infection. Methods. We performed a cohort study of patients who received piperacillin- tazobactam therapy for a P. aeruginosa infection that was susceptible to piperacillin- tazobactam during the period January 2000 - June 2004. Prior to February 2002, all patients received intermittent infusions of piperacillin- tazobactam ( 3.375 g intravenously for 30 min every 4 or 6 h); after this time, all patients received extended infusions of piperacillin- tazobactam ( 3.375 g intravenously for 4 h every 8 h). Data on demographic characteristics, disease severity, and microbiology were collected, and outcomes were compared between groups. Results. A total of 194 patients comprised the 2 study groups: 102 patients received extended infusions of piperacillin- tazobactam, and 92 patients received intermittent infusions of piperacillin- tazobactam. No differences in baseline clinical characteristics were noted between the 2 groups. Among patients with Acute Physiological and Chronic Health Evaluation - II scores >= 17, 14- day mortality rate was significantly lower among patients who received extended- infusion therapy than among patients who received intermittent- infusion therapy ( 12.2% vs. 31.6%, respectively; P = .04), and median duration of hospital stay after collection of samples for culture was significantly shorter for patients who received extended- infusion therapy than for patients who received intermittent- infusion therapy ( 21 days vs. 38 days; P . 02). Conclusions. These results indicate that extended- infusion piperacillin- tazobactam therapy is a suitable alternative to intermittent- infusion piperacillin- tazobactam therapy, and they strongly suggest that improved outcomes may be realized by administering extended- infusion piperacillin- tazobactam therapy to critically ill patients with P. aeruginosa infection.