Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates

Antimicrob Agents Chemother. 2016 Mar 25;60(4):2039-42. doi: 10.1128/AAC.02214-15. Print 2016 Apr.

Abstract

Pharmacokinetic modeling has often been applied to evaluate vancomycin pharmacokinetics in neonates. However, clinical application of the model-based personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a model-based patient-tailored dose of vancomycin in neonates. A model-based vancomycin dosing calculator, developed from a population pharmacokinetic study, has been integrated into the routine clinical care in 3 neonatal intensive care units (Robert Debré, Cochin Port Royal, and Clocheville hospitals) between 2012 and 2014. The target attainment rate, defined as the percentage of patients with a first therapeutic drug monitoring serum vancomycin concentration achieving the target window of 15 to 25 mg/liter, was selected as an endpoint for evaluating the clinical utility. The safety evaluation was focused on nephrotoxicity. The clinical application of the model-based patient-tailored dose of vancomycin has been demonstrated in 190 neonates. The mean (standard deviation) gestational and postnatal ages of the study population were 31.1 (4.9) weeks and 16.7 (21.7) days, respectively. The target attainment rate increased from 41% to 72% without any case of vancomycin-related nephrotoxicity. This proof-of-concept study provides evidence for integrating model-based antimicrobial therapy in neonatal routine care.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Drug Administration Schedule
  • Drug Monitoring / statistics & numerical data*
  • Female
  • Gestational Age
  • Humans
  • Infant
  • Infant, Newborn
  • Intensive Care Units, Neonatal
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Models, Statistical*
  • Patient Safety
  • Precision Medicine
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Vancomycin / administration & dosage
  • Vancomycin / pharmacokinetics*

Substances

  • Anti-Bacterial Agents
  • Vancomycin

Grants and funding

This work was supported by the Fundamental Research Funds and Young Scholars Program of Shandong University, the GRIP (Global Research in Pediatrics, European Commission FP7 project, grant agreement number 261060), and NeoVanc (European Commission FP7 project, grant agreement number 602041).