Clinical audit of gentamicin use by Bayesian pharmacokinetic approach in critically ill children

Area of Science:

• Pediatric Critical Care Medicine
• Pharmacokinetics and Pharmacodynamics
• Antibiotic Stewardship

Background:

• Critically ill children exhibit altered gentamicin pharmacokinetics (PK).
• Gentamicin dosing requires careful consideration of PK parameters like peak concentration (Cmax), trough concentration (Cmin), and area under the concentration-time curve (AUC).

Purpose of the Study:

• To audit gentamicin use in critically ill children using Bayesian pharmacokinetic modeling.
• To evaluate gentamicin exposure (Cmax, Cmin, AUC) across different pediatric age groups.
• To assess the incidence of acute kidney injury (AKI) in relation to gentamicin exposure.

Main Methods:

• Bayesian adaptive control models were used to estimate gentamicin Cmax and AUC0-t.
• Seventy-three critically ill children with available serum gentamicin concentrations were analyzed (961 doses, 143 concentrations).
• Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (pRIFLE) criteria were used to identify AKI.

Main Results:

• Gentamicin AUC0-24 was higher in younger children (neonates, infants) and decreased with age.
• Neonates had a higher risk of exceeding target Cmax levels (>10 mg/L).
• Children with augmented renal clearance had lower AUC0-24 and were less likely to achieve target levels; nearly one-third met pRIFLE criteria for AKI.

Conclusions:

• Higher initial gentamicin doses and peak concentrations were observed in neonates and infants compared to older critically ill children.
• There is a need for uniform, pediatric-specific standard treatment guidelines for gentamicin dosing.
• Optimizing gentamicin dosing in critically ill children is crucial for efficacy and minimizing nephrotoxicity.