Cefepime Pharmacokinetics in Critically Ill Pediatric Patients Receiving Continuous Renal Replacement Therapy

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Critical Care Medicine
• Pediatric Nephrology

Background:

• Continuous veno-venous hemodiafiltration (CVVHDF) is a common renal replacement therapy in pediatric intensive care units.
• Cefepime is a frequently used antibiotic in critically ill children.
• The optimal dosing of cefepime during CVVHDF in pediatric patients is not well established.

Purpose of the Study:

• To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets of cefepime in pediatric intensive care unit patients undergoing CVVHDF.
• To assess the achievement of target free cefepime concentrations (fT>1xMIC and fT>4xMIC) in this patient population.

Main Methods:

• Retrospective study of pediatric intensive care unit patients receiving cefepime during CVVHDF.
• Calculation of free drug concentration above one time the minimum inhibitory concentration (MIC) (fT>1xMIC) and four times a presumed MIC (fT>4xMIC) of 8 μg/ml.
• Analysis of cefepime doses administered (48 to 64 mg/kg every 6 to 12 hours).

Main Results:

• Three out of four patients achieved 100% fT>1xMIC.
• The fourth patient achieved 98% fT>1xMIC.
• All patients received cefepime doses ranging from 48 to 64 mg/kg every 6 to 12 hours.

Conclusions:

• The studied cefepime dosing regimens were generally effective in achieving target PK/PD exposures in pediatric patients on CVVHDF.
• Therapeutic drug monitoring should be considered to optimize cefepime therapy in critically ill pediatric patients receiving CVVHDF.
• Further studies are warranted to confirm optimal dosing strategies.