Vancomycin AUC0–24 estimation using first‐order pharmacokinetic methods in pediatric patients

Abstract

AbstractIntroductionThe 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.ObjectivesTo describe the interplay of vancomycin dose, AUC0–24, and Cmin using first‐order equations within four pediatric age groups.MethodsThis 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.ResultsOverall, 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.ConclusionsOur 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.