Optimizing Vancomycin Use Through 2‐Point AUC‐Based Therapeutic Drug Monitoring in Pediatric Patients

Abstract

The 24-hour vancomycin area under the serum concentration-time curve (AUC₂₄ ) divided by the minimum inhibitory concentration (MIC) (AUC₂₄ /MIC) is more closely related to patient outcomes than serum trough concentrations (C_trough ). Two-point simplified equations for calculating AUC based on serum peak concentrations (C_peak ) and C_trough , named equation A (EqA) and equation B (EqB), have recently been adopted into clinical use for adult pediatric patients. We aimed to find the agreement between predicted AUC₂₄ using the reference method (ref) relative to EqA and EqB and the correlation between C_trough and AUC₂₄ . From June to December 2018, 43 pediatric patients with normal renal function, receiving 15 mg/kg of vancomycin intravenously every 6 hours, were enrolled. The pediatric patients' median age was 2.2 years (range 0.1-15.3). At steady state, vancomycin C_peak and C_trough were measured at 2 hours after infusion completion and within 30 minutes before the next dosing, respectively. AUC₂₄ was estimated using ref, EqA, and EqB. From Bland-Altman analysis, the 2 AUC₂₄ s estimated by ref and EqA showed less bias than those estimated by ref and EqB (bias 1.3 and -72.1 mg⋅h/L, respectively). C_trough and AUC₂₄ using either ref or EqA were correlated more closely (r² = 0.94) than with EqB (r² = 0.86). Assuming a vancomycin MIC of 1 mg/L, an AUC₂₄ ≥400 mg⋅h/L was targeted. Regardless of the method used, AUC₂₄ ≥400 mg⋅h/L was never seen with C_trough <8 mg/L but was always seen with C_trough >10 mg/L. In conclusion, EqA based on the 2 measured serum concentrations was sufficiently accurate for AUC₂₄ estimation. C_trough >10 mg/L correlated highly to AUC₂₄ ≥400 mg⋅h/L.