OBJECTIVE Vancomycin carries risks of treatment failure and emergent resistance with underexposure and renal toxicity with overexposure. Children with overweight or obesity may have altered pharmacokinetics. We aimed to examine how body weight metrics influence vancomycin serum concentrations and to evaluate alternative dosing strategies. METHODS This was a multicenter retrospective cohort study across 3 large, academic hospitals. Patients aged 2 to 18 years old who received ≥3 doses of intravenous vancomycin were included. Weight metrics included total body weight, adjusted body weight, ideal body weight, body surface area, and allometric weight. Outcomes included vancomycin concentration and ratios of area under the curve (AUC) to minimum inhibitory concentration (MIC). Regression analyses were used to examine which body-weight identifier predicted outcomes. RESULTS Of the 1099 children, 45% were girls, mean age was 9.0 (SD = 5.4) years, 14% had overweight, and 17% had obesity. Seventy-five percent of children had vancomycin concentrations in the subtherapeutic range by trough <10 µg/mL, and 63% had a ratio of AUC to MIC <400 μg-hr/mL. Three percent had a supratherapeutic initial trough >20 µg/mL or ratio of AUC to MIC >600 μg-hr/mL. Serum vancomycin concentrations were higher in children with overweight or obesity compared with children who were at a normal weight or underweight; the mean ratio of AUC to MIC also trended higher in the groups with overweight or obesity. CONCLUSIONS Most children received vancomycin regimens that produced suboptimal trough levels. Children with overweight or obesity experienced higher vancomycin trough levels than children of normal weight despite receiving lower total body weight dosing. Using the ratio of AUC to MIC was a better measure of drug exposure.
CONTEXT: Vancomycin is a medication with potential for significant harm with both overdosing and underdosing. Obesity may affect vancomycin pharmacokinetics and is increasingly common among children. OBJECTIVE: We aimed to determine if children with overweight or obesity have increased vancomycin trough concentrations with total body weight (TBW) dosing compared with children with normal weight. DATA SOURCES: We conducted a search of Medline and Medline In-Process & Other Non-Indexed Citations from 1952 (the year vancomycin was discovered) to November 2017. STUDY SELECTION: Search terms included vancomycin, body weight, and body composition terms and were limited to children. Studies were reviewed and screened by ≥2 reviewers. DATA EXTRACTION: The primary outcome was vancomycin level. Data were extracted by 2 reviewers. We performed quality assessment using the Newcastle-Ottawa quality assessment scale. RESULTS: We identified 271 records. After abstract and full-text screening, we identified 7 studies for full review. Six of the 7 studies used a matched case-control design, although there was significant variation in study methodology. Four of the 7 studies were included in a meta-analysis, which revealed a small but significant difference in vancomycin trough levels between children with normal weight and children with overweight or obesity when dosed by using TBW (N = 521; mean difference 2.2 U [95% confidence interval: 1.0–3.4]). CONCLUSIONS: High-quality data to guide vancomycin dosing in children with obesity are lacking. More studies evaluating dosing strategies in children with obesity are warranted because using TBW to dose vancomycin may lead to higher vancomycin concentrations and potential toxicity.