Pediatric Assessment of Vancomycin Empiric Dosing (PAVED): a Retrospective Review.

Abstract

Pediatric studies and anecdotal experience suggest that current empiric vancomycin dosing does not reach serum trough concentration targets of at least 10 mg/L for uncomplicated infections or 15-20 mg/L for serious or complicated infections. This study reviewed vancomycin dosing and serum concentrations to (i) determine the proportion of patients who reached initial target concentrations; (ii) describe pharmacokinetic parameters; and (iii) compare patient-specific area-under-the-curve (AUC) values to population estimates using the Rodvold equation. Following ethics approval, data were extracted from medical records of 200 patients aged 1 month-18 years, who received intravenous (IV) vancomycin and had at least two pharmacokinetically evaluable serum concentrations. Trough vancomycin concentrations of 10-15 and 15-20 mg/L were achieved in 25 (29%) and 2 (2%) patients receiving vancomycin 15 mg/kg IV every 6 h (q6 h) and 22 (20%) and 9 (8%) patients receiving vancomycin 20 mg/kg IV every 8 h (q8 h), respectively. Patients were stratified into four age groups (1 month-1 year, 1-6 years, 6-13 years and 13-18 years). Median (IQR) pharmacokinetic parameters were elimination rate constant 0.25 (0.09), 0.29 (0.07), 0.24 (0.10) and 0.22 (0.07) h(-1); volume of distribution 0.56 (0.20), 0.61 (0.21), 0.47 (0.26) and 0.49 (0.22) L/kg; and half-life 2.8 (1.1), 2.4 (0.5), 2.9 (1.1) and 3.2 (1.0) h, respectively. Median (IQR) AUCs were 458 (170), 338 (132), 478 (215) and 513 (179) mg h/L and population-estimated AUCs were 67 (44), 108 (70), 299 (102) and 454 (103) mg h/L (p < 0.05 for all groups). Based on these findings, we recommend vancomycin 70 and 90 mg/kg/day divided q6 h for troughs of 10-15 and 15-20 mg/L, respectively (patients 1 month-6 years) and 60 mg/kg/day divided q8 h and 70 mg/kg/day divided q6 h, respectively (patients >6 years) to undergo further testing as initial dosing regimens. Furthermore, population estimates grossly underestimate vancomycin AUC in patients 1-18 years old and thus patient-specific parameters are required.