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

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.