Comparison of the pharmacokinetics of piperacillin and sulbactam during intermittent and continuous intravenous infusion

Abstract

Background: The antibacterial effect of piperacillin/sulbactam depends on the time of drug concentration above the minimal inhibitory concentration (MIC). Therefore, continuous infusion (CI) may be a more rational approach than standard intermittent short-term infusion (SI). The study investigated whether CI achieves effective drug concentrations comparable with SI.

Methods: Seven intensive care unit patients received either piperacillin/sulbactam as 4/1 g intravenous infusion over 15-20 min every 8 h or as 4/1 g intravenous loading dose (15-20 min) followed by 8/2 g intravenous CI per 24 h. After 2 days, regimes were crossed over.

Results: Pharmacokinetic parameters (mean +/- SD) for SI piperacillin/sulbactam were: (1) peak serum concentration: piperacillin 231 +/- 66 mg/l, sulbactam 53.1 +/- 15.0 mg/l; (2) minimum serum concentration: piperacillin 11.5 +/- 14.8 mg/l, sulbactam 4.2 +/- 3.5 mg/l; (3) clearance: piperacillin 197 +/- 72 ml/min (CI 269 +/- 123 ml/min), sulbactam 167 +/- 61 ml/min (CI 212 +/- 109 ml/min); (4) half-life: piperacillin 2.4 +/- 1.2 h, sulbactam 3.1 +/- 1.6 h. Steady-state concentrations during CI were 25.5 +/- 14.5 mg/l for piperacillin and 8.0 +/- 3.7 mg/l for sulbactam. Average serum concentrations were comparable in both regimens.

Conclusion: A large German survey demonstrated that approximately 89% of Pseudomonas aerugionsa have an MIC < or =16 mg/l and approximately 82% have an MIC < or =8 mg/l. According to this threshold, appropriate anti-bacterial concentrations of piperacillin/sulbactam were achievable with CI. CI dosing has the additional advantage that less drug is necessary. Further prospective studies are warranted to compare the clinical efficacy of CI and SI regimens in bacterial infections.