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Pediatric Assessment of Vancomycin Empiric Dosing (PAVED): a Retrospective Review
Daniel Rainkie1, Mary H H Ensom, Roxane Carr
1Children's and Women's Health Centre of British Columbia, Vancouver, BC, Canada.
Insights
Current vancomycin dosing in children often fails to achieve therapeutic serum trough concentrations. This study suggests revised dosing regimens for vancomycin to improve treatment efficacy in pediatric patients.
Area of Science:
- Pediatric pharmacology
- Infectious disease management
- Pharmacokinetics and pharmacodynamics
Background:
- Pediatric vancomycin dosing regimens frequently do not achieve target serum trough concentrations (10-20 mg/L).
- This is a critical issue for treating serious or uncomplicated infections in children.
Purpose of the Study:
- To evaluate the proportion of pediatric patients achieving target vancomycin serum concentrations.
- To characterize pharmacokinetic parameters in pediatric patients.
- To compare patient-specific area-under-the-curve (AUC) values with population estimates.
Main Methods:
- Retrospective review of medical records for 200 pediatric patients (1 month-18 years) receiving intravenous vancomycin.
- Inclusion criteria required at least two pharmacokinetically evaluable serum vancomycin concentrations.
- Patients were stratified into four age groups for analysis.
Main Results:
- Low rates of achieving target trough concentrations (10-15 mg/L and 15-20 mg/L) were observed with standard dosing (15 mg/kg q6h and 20 mg/kg q8h).
- Significant differences in pharmacokinetic parameters (elimination rate constant, volume of distribution, half-life) were noted across age groups.
- Patient-specific AUC values were significantly higher than population-estimated AUCs, indicating underestimation by standard models.
Conclusions:
- Current empiric vancomycin dosing in pediatric patients is often inadequate.
- Revised dosing recommendations (e.g., 70-90 mg/kg/day for younger children, 60-70 mg/kg/day for older children) are proposed for further investigation.
- Patient-specific pharmacokinetic assessments are crucial for optimizing vancomycin therapy in children aged 1-18 years.
Background:
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.
Objectives:
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.
Methods:
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.
Results:
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).
Conclusions:
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.
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