Determination of vancomycin pharmacokinetics in neonates to develop practical initial dosing recommendations

Area of Science:

• Neonatal pharmacokinetics
• Infectious disease pharmacotherapy
• Pediatric critical care medicine

Background:

• Neonatal vancomycin dosing faces challenges due to pharmacokinetic variability and lack of consensus on target trough concentrations.
• Establishing optimal vancomycin dosing regimens is crucial for effective treatment in neonatal intensive care units (NICUs).

Purpose of the Study:

• To determine vancomycin pharmacokinetics in neonates.
• To evaluate different vancomycin dosing regimens for neonates.
• To identify practical initial dosing recommendations for common target trough concentrations.

Main Methods:

• Retrospective evaluation of 50 neonates receiving vancomycin with steady-state levels.
• Calculation of mean pharmacokinetic values using first-order pharmacokinetic equations.
• Monte Carlo simulation to assess dosing regimens against target trough concentrations (15-20 mg/L, 5-20 mg/L, ≤20 mg/L).

Main Results:

• Intermittent vancomycin dosing of 9-12 mg/kg every 8 hours (q8h) showed the highest probability of achieving 15-20 mg/L trough concentrations.
• Continuous infusion (10 mg/kg loading dose, then 25-30 mg/kg/day) offered the best overall probability of target attainment.
• Initial intermittent dosing of 9-15 mg/kg every 12 hours (q12h) was optimal for target troughs of 5-20 mg/L and ≤20 mg/L.

Conclusions:

• A practical initial vancomycin dose of 10 mg/kg i.v. q12h is optimal for target trough concentrations of 5-20 mg/L or ≤20 mg/L.
• The same initial dose (10 mg/kg) q8h is optimal for target trough concentrations of 15-20 mg/L.
• Due to significant interpatient pharmacokinetic variability, serum concentration monitoring is recommended for neonates when targeting 15-20 mg/L or 5-20 mg/L trough concentrations.