Population Pharmacokinetic Analysis and Pharmacodynamic Evaluation of Sulbactam in Pediatric Patients: Dosing Suggestions for Acinetobacter baumannii Infections.

Abstract

Background: This study aims to develop a population pharmacokinetic (PK) model of sulbactam in pediatric patients using pooled data analysis, and to optimize dosing regimens against Acinetobacter baumannii infections.

Methods: Publications were systematically identified with MEDLINE for collecting sulbactam PK data in pediatric patients. Sulbactam PK model was developed using plasma concentration-time data gained from identified literature works. Based on the model, we estimated the probability of attaining the pharmacodynamic (PD) target against A. baumannii.

Results: The data were adequately described by 2-compartment model. Age was a statistically significant covariate in clearance. Aiming for the PD target of 60% of time above minimum inhibitory concentration in free drug concentrations (fT > MIC), the breakpoint MICs were increased by extending infusion time from 0.5 to 4 hours. The breakpoint MICs for 4-hour infusion regimens of 25 mg/kg 4 times daily (100 mg/kg/day) achieved 4 μg/mL in infants (4 weeks to 11 months), children (1-6 years old) and pediatrics (7-16 years old). The breakpoint values for 4-hour infusions of 50 mg/kg 4 times daily (200 mg/kg/day) achieved 8 μg/mL (intermediate range of Clinical and Laboratory Standards Institute criteria) in all age groups.

Conclusions: This population PK analysis and PD evaluation suggest that higher dosing regimen, especially with extended infusion time, should be reasonable for treating A. baumannii infections in pediatric patients.