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

• Published in: Paediatric drugs Vol. 17; no. 3; pp. 245 - 253
• Main Authors: Rainkie, Daniel, Ensom, Mary H. H., Carr, Roxane
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2015; Springer; Springer Nature B.V
• Subjects: Adolescent; Analysis; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Area Under Curve; Child; Child, Preschool; Dosage and administration; Drug utilization; Female; Half-Life; Humans; Infant; Internal Medicine; Male; Medicine; Medicine & Public Health; Methods; Original Research Article; Pediatric pharmacology; Pediatrics; Pharmacokinetics; Pharmacotherapy; Retrospective Studies; Vancomycin; Vancomycin - administration & dosage; Vancomycin - pharmacokinetics; Vancomycin - therapeutic use; Canada; Continuous Renal Replacement Therapy; Minimum Inhibitory Concentration; Trough Concentration; Vancomycin; Vancomycin Concentration
• ISSN: 1174-5878; 1179-2019
• DOI: 10.1007/s40272-015-0122-8

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.