Abstract: AIM: To evaluate the pharmacodynamic profiling of prolonged and continuous infusion dosing regimens of Piperacillin-tazobactam against gram-negative bacteria.METHODS: Minimum inhibitory concentrations for Escherichia coli,Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa from Jan 2008 to Jun 2008 in hospital were determined. A 10000-subject Monte Carlo simulation was performed to calculate pharmacodynamic target attainment for prolonged, continuous and traditional dosing regimens of Piperacillin-tazobactam.RESULTS: Against Escherichia coli and Klebsiella pneumoniae, only Piperacillin-tazobactam 4.5 g every 6 hours (3-h infusion) achieved cumulative fraction of response (CFR) of greater than 90%, 98.4% and 91.0%,respectively. No regimen achieved optimum CFR against Acinetobacter baumannii and Pseudomonas aeruginosa. Continuous infusion Piperacillin-tazobactam 9.0 g every 24 hours led to higher CFR than 4.5 g every 8 hours (30-min infusion). Compared with traditional regimen (30-min infusion), prolonged infusion Piperacillin-tazobactam 4.5 g every 8 hours and 4.5 g every 6 hours yielded greater CFR. CONCLUSION: Prolonged and continuous infusion Piperacillin-tazobactam is superior to traditional regimens and should be recommended as empirical therapy against common gram-negative bacteria.

Key words: Monte Carlo simulation, Piperacillin-tazobactam, Gram-negative bacteria, Pharmacodynamics