Piperacillin Population Pharmacokinetics in Children Supported With Extracorporeal Membrane Oxygenation

Area of Science:

• Pediatric Critical Care Medicine
• Pharmacokinetics and Pharmacodynamics
• Antimicrobial Dosing Strategies

Background:

• Optimizing antibiotic dosing is crucial for critically ill children, especially those on extracorporeal membrane oxygenation (ECMO).
• Piperacillin pharmacokinetics (PK) can be altered by ECMO and varying renal function.
• Achieving target drug concentrations (100% free time above minimum inhibitory concentration) is essential for effective treatment.

Purpose of the Study:

• To characterize piperacillin population PK in critically ill children with and without ECMO.
• To optimize piperacillin dosing regimens to achieve PK targets.
• To inform dosing adjustments based on renal function and ECMO status.

Main Methods:

• A post hoc analysis of a population PK modeling and simulation study.
• Included 33 children on ECMO and 50 non-ECMO controls.
• Evaluated continuous infusion (300 mg/kg/d) and intermittent infusion (75 mg/kg every 6 hours) regimens.

Main Results:

• A one-compartment linear model described piperacillin PK, influenced by weight and eGFR.
• ECMO increased the volume of distribution by 34% in an 11-kg patient.
• Continuous infusion of 300 mg/kg/d achieved target attainment in most patients; 400 mg/kg/d was needed for eGFR > 200 mL/min/1.73 m2.

Conclusions:

• Continuous infusion piperacillin at 300 mg/kg/d reliably achieves PK targets in critically ill children, including those on ECMO.
• Dose escalation to 400 mg/kg/d is necessary for patients with augmented renal clearance (eGFR > 200 mL/min/1.73 m2).
• These findings support optimized piperacillin dosing strategies in pediatric intensive care units.