Determination of Vancomycin Pharmacokinetics in Neonates To Develop Practical Initial Dosing Recommendations

Abstract

f Variability in neonatal vancomycin pharmacokinetics and the lack of consensus for optimal trough concentrations in neonatal intensive care units pose challenges to dosing vancomycin in neonates. Our objective was to determine vancomycin pharmacokinetics in neonates and evaluate dosing regimens to identify whether practical initial recommendations that targeted trough concentrations most commonly used in neonatal intensive care units could be determined. Fifty neonates who received vancomycin with at least one set of steady-state levels were evaluated retrospectively. Mean pharmacokinetic values were determined using first-order pharmacokinetic equations, and Monte Carlo simulation was used to evaluate initial dosing recommendations for target trough concentrations of 15 to 20 mg/liter, 5 to 20 mg/liter, and <20 mg/liter. Monte Carlo simulation revealed that dosing by mg/kg of body weight was optimal where intermittent dosing of 9 to 12 mg/kg intravenously (i.v.) every 8 h (q8h) had the highest probability of attaining a target trough concentration of 15 to 20 mg/liter. However, continuous infusion with a loading dose of 10 mg/kg followed by 25 to 30 mg/kg per day infused over 24 h had the best overall probability of target attainment. Initial intermittent dosing of 9 to 15 mg/kg i.v. q12h was optimal for target trough concentrations of 5 to 20 mg/liter and <20 mg/ liter. In conclusion, we determined that the practical initial vancomycin dose of 10 mg/kg vancomycin i.v. q12h was optimal for vancomycin trough concentrations of either 5 to 20 mg/liter or <20 mg/liter and that the same initial dose q8h was optimal for target trough concentrations of 15 to 20 mg/liter. However, due to large interpatient vancomycin pharmacokinetic variability in neonates, monitoring of serum concentrations is recommended when trough concentrations between 15 and 20 mg/liter or 5 and 20 mg/liter are desired.

Vancomycin is commonly under‐dosed in critically ill children and neonates

“…Finally, a potential limitation of this study is that the achievement of steady state was not confirmed. However, paediatric drug formularies recommend determining vancomycin concentrations between 24–48 hours based on the fact that steady state is likely to have occurred …”

“…However, paediatric drug formularies recommend determining vancomycin concentrations between 24-48 hours based on the fact that steady state is likely to have occurred. 52,53 It is clear that individualised dosing is needed in critically ill children…”

Australia-wide Point Prevalence Survey of Antimicrobial Prescribing in Neonatal Units

“…18,19 For gentamicin in particular, the diversity is similar to findings in UK neonatal units. [29][30][31] An Australasian working group, including many contributors to this study, is currently formulating consensus therapeutic guidelines for vancomycin and gentamicin dosing on the dosing in children and neonates. The impact of these guidelines could be a focus in a future PPS, including collection of therapeutic drug monitoring data.…”

A propensity-matched cohort study of vancomycin-associated nephrotoxicity in neonates

“…Additionally, SCr ≥1.5 mg/dL persisting ≥48 h was considered an AKI 32. A SCr increase of ≥125% (≥0.15 mg/dL within a 48 h time frame) was considered a ‘potential’ AKI 33. Vancomycin-associated nephrotoxicity was defined as an event occurring between the first dose to 72 h after the last dose in a clinical episode.…”