Vancomycin AUC0-24 estimation using first-order pharmacokinetic methods in pediatric patients.

Abstract

The optimal dosing and monitoring of vancomycin in pediatrics is still unknown but has evolved to emphasize area under the curve over 24 h (AUC0-24) over minimum concentration (Cmin) monitoring. Real-world data supporting the feasibility of two-concentration kinetics with first-order equations for the estimation of vancomycin AUC0-24 in pediatric patients are lacking. To describe the interplay of vancomycin dose, AUC0-24, and Cmin using first-order equations within four pediatric age groups. This is a single-center, retrospective cohort study analyzing pediatric patients (<18 years) receiving intravenous vancomycin between 2020 and 2022. Included patients received at least 24 h of intravenous vancomycin with two concentrations obtained within 96 h of therapy initiation. Patients with baseline renal dysfunction were excluded. Patients were divided into four age categories: neonates (≤28 days), infants (29 days to <1 year), children (1-12 years), and adolescents (13-17 years). First-order equations were utilized to estimate pharmacokinetic parameters and AUC0-24. Overall, 219 patients (median age of 6 years [IQR 1-12]) met inclusion criteria. The median vancomycin daily dose was 30 mg/kg in neonates, 70 mg/kg in infants and children, and 52 mg/kg in adolescents. Median Cmin and AUC0-24 values among all age groups were 8.68 mg/L and 505 mg * h/L, respectively. For AUC0-24 values outside of the therapeutic range (400-600 mg * h/L), more values were SUPRAtherapeutic (>600 mg * h/L) than SUBtherapeutic (<400 mg * h/L). The overall trend within our data showed suboptimal correlation between Cmin and AUC0-24. However, 71% of patients with Cmin values of 5-10 mg/L had an AUC0-24 within the therapeutic range of 400-600 mg * h/L, whereas 23 patients (92%) with a SUPRAtherapeutic AUC0-24 had a Cmin value ≥15 mg/L. Approximately 10% of patients experienced acute kidney injury. Our data describe the relationship between vancomycin dose, Cmin, and AUC0-24 in pediatric patients. We demonstrated the feasibility of using first-order equations to estimate AUC0-24, using two concentrations obtained at steady state to monitor efficacy and safety in pediatric patients receiving intravenous vancomycin. Our data showed suboptimal correlation between AUC0-24 and Cmin, which indicates that Cmin should not be used as a surrogate marker for a therapeutic AUC0-24 in pediatric patients. In alignment with the 2020 vancomycin consensus guidelines, we suggest utilizing AUC0-24 for efficacy and safety monitoring.