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). We 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, randomized trial of EI versus IB of PTZ was conducted in children aged 1 month to 18 years. PTZ dosing was 100 mg/kg/dose of piperacillin intravenously every 8 hours. Patients were randomly assigned to receive EI (4-h infusion) or IB group (30-min infusion). Primary outcome 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 were 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 method. In settings with increased piperacillin MICs, this approach should be implemented, particularly during the empirical treatment period.Reference:
Chongcharoenyanon T, Wacharachaisurapol N, Anugulruengkitt S, Maimongkol P, Anunsittichai O, Sophonphan J, Chatsuwan T, Puthanakit T. Comparison of Piperacillin Plasma Concentrations in a Prospective Randomized Trial of Extended Infusion versus Intermittent Bolus of Piperacillin/Tazobactam in Paediatric Patients. Int J Infect Dis. 2021 May 21:S1201-9712(21)00446-X. doi: 10.1016/j.ijid.2021.05.044. Epub ahead of print. PMID: 34029707.