Cefepime population pharmacokinetics and dosing regimen optimization in critically ill children with different renal...

Area of Science:

• Pharmacology
• Pediatric Critical Care
• Pharmacokinetics

Background:

• Cefepime is a vital antibiotic in pediatric intensive care units.
• Critically ill children exhibit variable pharmacokinetic (PK) parameters, necessitating dose adjustments.
• Optimizing cefepime dosing is crucial for effective treatment in this population.

Purpose of the Study:

• To develop a population pharmacokinetic (PK) model for cefepime in critically ill children.
• To optimize initial cefepime dosing regimens for individual patients.
• To identify key covariates influencing cefepime PK in pediatric patients.

Main Methods:

• A population PK model was constructed using nonlinear mixed-effects modeling.
• Cefepime plasma concentrations were measured via high-performance liquid chromatography.
• Monte Carlo simulations were performed to evaluate dosing strategies against a target of 100% time above minimum inhibitory concentration (fT > MIC).

Main Results:

• A one-compartment model best described the cefepime concentration data.
• Body weight (allometrically scaled) and estimated glomerular filtration rate (eGFR) significantly influenced clearance.
• Simulations indicated that 100 mg/kg/d q12h (30-min infusion) is suitable for renal failure, while continuous infusion is better for normal/augmented renal clearance.

Conclusions:

• Cefepime dosing must be tailored to individual renal function in critically ill children.
• Continuous infusions are preferred for patients with normal or augmented renal clearance.
• Intermittent infusions may be adequate for children with acute renal failure; therapeutic drug monitoring is essential due to cefepime's narrow therapeutic window.