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

J Clin Pharmacol. 2019 Dec;59(12):1597-1605. doi: 10.1002/jcph.1498. Epub 2019 Jul 24.

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 (Ctrough ). Two-point simplified equations for calculating AUC based on serum peak concentrations (Cpeak ) and Ctrough , 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 Ctrough 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 Cpeak and Ctrough 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). Ctrough 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 Ctrough <8 mg/L but was always seen with Ctrough >10 mg/L. In conclusion, EqA based on the 2 measured serum concentrations was sufficiently accurate for AUC24 estimation. Ctrough >10 mg/L correlated highly to AUC24 ≥400 mg⋅h/L.

Keywords: Area under the serum concentration-time curve; Equation; Outcome; Pediatric; Trough concentration; Vancomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Area Under Curve
  • Child
  • Child, Preschool
  • Drug Monitoring / methods
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests / methods
  • Prospective Studies
  • Staphylococcal Infections / drug therapy
  • Vancomycin / pharmacokinetics*
  • Vancomycin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Vancomycin