Dose Optimization of Piperacillin for Pseudomonas aeruginosa Infection in Febrile Neutropenic Pediatric Patients

Abstract

Background: Febrile neutropenic pediatric oncology patients require aggressive antimicrobial therapy against Pseudomonas aeruginosa, but standard piperacillin dosing may provide suboptimal exposure due to altered pharmacokinetics in this population. Objective: This simulation-based study aimed to evaluate the impact of loading doses, maintenance dose timing, and infusion duration on piperacillin pharmacodynamic target attainment in pediatric febrile neutropenia. Methods: Monte Carlo simulations were performed using a published population pharmacokinetic model. A virtual cohort of 5000 children across five weight groups (8–52 kg) was generated. Probability of target attainment (PTA) was assessed for two stringent pharmacodynamic targets: 50% fT > 4 × MIC and 100% fT > MIC against Pseudomonas aeruginosa at the EUCAST breakpoint MIC of 16 mg/L. Simulated regimens varied by loading dose, infusion duration, and timing of maintenance dose administration. Results: Standard intermittent dosing (75–100 mg/kg every 6 h) failed to achieve adequate PTA for either target, even with loading doses up to 200 mg/kg. Accelerated maintenance dosing (3 h post-loading dose) with extended infusions achieved optimal PTA (> 90%) for the 50% fT > 4 × MIC target in patients ≥ 22 kg using loading doses of 100–150 mg/kg followed by 100 mg/kg every 6 h over 3 h. For the 100% fT > MIC target, only continuous infusion (300 mg/kg/day) with appropriate loading doses achieved 100% PTA across all weights. Conclusion: Conventional piperacillin dosing is insufficient in pediatric patients with febrile neutropenia. Loading dose with accelerated maintenance dosing achieves 50% fT > 4 × MIC, while continuous infusion is essential for 100% fT > MIC target attainment.