Individualized vancomycin dosing in infants: prospective evaluation of an online dose calculator

Amanda L. Wilkins, Tony Lai, Xiao Zhu, Srinivas Bolisetty, Roberto Chiletti, Noel Cranswick, Kaya Gardiner, Rodney Hunt, Atul Malhotra, Brendan McMullan, Bhavesh Mehta, Joanna Michalowski, Himanshu Popat, Meredith Ward, Stephen Duffull, Nigel Curtis, Amanda Gwee

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Empiric vancomycin dosing regimens fail to achieve recommended target trough concentrations of 10-20 mg/L in the majority of infants. This study assessed the performance of a model-based dosing calculator (Vanc App) in achieving target vancomycin concentrations at first steady-state level. Methods: This was a multicenter prospective study in four tertiary pediatric hospitals over an 18-month period. Infants aged 0-90 days with suspected Gram-positive sepsis requiring empiric vancomycin treatment were included if they did not meet any of the exclusion criteria: post-menstrual age (PMA) <25 weeks, weight <500 g, glycopeptide allergy, receiving extracorporeal membrane oxygenation, vancomycin use within the previous 72 h, and renal impairment. The Vanc App used a published population pharmacokinetic model to generate a dose based on the infant's PMA, weight, creatinine, and target vancomycin concentration. Results: A total of 40 infants were included; 40% were female, median (range) weight was 2505 (700-4460) g and median (range) PMA was 37.4 (25.7-49.0) weeks. The median (range) vancomycin dose was 45 (24-79) mg/kg/day. All infants had trough vancomycin concentrations measured at steady-state (24-<48 hours) and 30 (75%) infants achieved target concentrations. Five infants had supratherapeutic (median 25, range 21-38 mg/L) and five had subtherapeutic (median 6, range <5-9 mg/L) concentrations. An area under the concentration-time curve (AUC0-24) of 400-650 mg/L.h was achieved in 33 (83%) infants. There were no infusion-related reactions or nephrotoxicity. Conclusion: Individualized intermittent vancomycin dosing using a model-based online calculator resulted in 75% and 83% of infants achieving target trough and AUC0-24, respectively, at first steady-state level. There were no vancomycin-related nephrotoxicity or infusion-related reactions.

Original languageEnglish
Article number106728
Number of pages7
JournalInternational Journal of Antimicrobial Agents
Volume61
Issue number3
DOIs
Publication statusPublished - Mar 2023

Keywords

  • individualized dosing
  • infants
  • neonates
  • pharmacokinetics
  • vancomycin

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