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Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0b013e318286378e
Antimicrobial Reviews

Improved Vancomycin Dosing in Children Using Area Under the Curve Exposure

Le, Jennifer PharmD, MAS, FCCP, BCPS-ID*†; Bradley, John S. MD*‡; Murray, William PharmD; Romanowski, Gale L. PharmD; Tran, Tu T. PharmD; Nguyen, Natalie PharmD*; Cho, Susan PharmD*; Natale, Stephanie PharmD; Bui, Ivilynn BS; Tran, Tri M. BS (Candidate); Capparelli, Edmund V. PharmD*

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Abstract

Background: Our objectives were to (1) determine the pharmacokinetic indices of vancomycin in pediatric patients; and (2) compare attainment of 2 target exposures: area under curve (AUC) / minimum inhibitory concentration (MIC) ≥400 and trough concentration ≥15 mcg/mL.

Methods: The population-based pharmacokinetic modeling was performed using NONMEM 7.2 for children ≥3 months old who received vancomycin for ≥48 hours from 2003 to 2011. A 1-compartment model with first-order kinetics was used to estimate clearance, volume of distribution and AUC. Empiric Bayesian post hoc individual parameters and Monte Carlo simulations (N = 11,000) were performed.

Results: Analysis included 702 patients with 1660 vancomycin serum concentrations. Median age was 6.6 (interquartile range 2.2–13.4) years, weight 22.7 (12.6–46) kg and baseline serum creatinine 0.40 (0.30–0.60) mg/dL. Final model pharmacokinetic indices were clearance (L/h) = 0.248 * Wt0.75 * (0.48/serum creatinine)0.361 * (ln(age)/7.8)0.995 and volume of distribution (L) = 0.636 * Wt. Using these parameters and the observed MIC distribution, Monte Carlo simulation indicated that the initial median dose of 44 (39–52) mg/kg/day was inadequate in most subjects. Regimens of 60 mg/kg/day for subjects ≥12 years old and 70 mg/kg/day for those <12 years old achieved target AUC/MIC in ~75% and trough concentrations ≥15 in ~45% of virtual subjects. An AUC/MIC ~400 corresponded to trough concentration ~8 to 9 mcg/mL.

Conclusions: Targeted exposure using vancomycin AUC/MIC, compared with trough concentrations, is a more realistic target in children. Depending on age, serum creatinine and MIC distribution, vancomycin in a dosage of 60 to 70 mg/kg/day was necessary to achieve AUC/MIC ≥ 400 in 75% of patients.

© 2013 Lippincott Williams & Wilkins, Inc.

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