Comparison of piperacillin plasma concentrations in a prospective randomised trial of extended infusion versus intermittent bolus of piperacillin/tazobactam in paediatric patients

Objectives: To be effective, piperacillin/tazobactam (PTZ) unbound plasma levels need to be above the minimum inhibitory concentration (MIC) at least 50% of the time between dosing intervals (50% fT>MIC). This study aimed to compare the plasma piperacillin concentrations at the mid-dosing intervals (Cmid, 50% fT) and the proportion of patients achieving 50% fT>MIC between extended infusion (EI) and intermittent bolus (IB) methods in children. Methods: A prospective, randomised trial of EI versus IB of PTZ was conducted in children aged 1 month to 18 years. The PTZ dose was 100 mg/kg intravenously every 8 h. Patients were randomly assigned to receive EI (4-h infusion) or IB (30-min infusion). The primary outcome that was measured was plasma piperacillin Cmid. Results: Ninety patients with a median age (IQR) of 48 months (16–127) were enrolled. The most common indication for PTZ use was pneumonia (32.2%). Geometric mean (95% CI) plasma piperacillin Cmid of EI versus IB was 51.9 mg/L (40.6–66.6) versus 6.0 mg/L (4.2–8.6) (P < 0.01). The EI group had a trend of higher proportion of patients who achieved 50% fT>4xMIC (72.7% versus 30.0%; P = 0.06). Conclusions: PTZ administration with EI resulted in a higher Cmid compared with IB. In settings with increased piperacillin MICs, this approach should be implemented, particularly during the empirical treatment period.