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

Int J Infect Dis. 2021 Jul:108:102-108. doi: 10.1016/j.ijid.2021.05.044. Epub 2021 May 21.


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.

Keywords: Extended infusion; Multidrug-resistant organisms; Paediatrics; Piperacillin; Therapeutic drug monitoring.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Anti-Bacterial Agents* / therapeutic use
  • Child
  • Child, Preschool
  • Humans
  • Microbial Sensitivity Tests
  • Penicillanic Acid
  • Piperacillin*
  • Piperacillin, Tazobactam Drug Combination
  • Prospective Studies


  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Penicillanic Acid
  • Piperacillin