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Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0b013e3182a26774
Antimicrobial Reviews

A Randomized Controlled Trial of a Vancomycin Loading Dose in Children

Demirjian, Alicia MD, MMSc*; Finkelstein, Yaron MD†‡§¶; Nava-Ocampo, Alejandro MD§¶; Arnold, Alana PharmD, BCPS AQ-ID; Jones, Sarah PharmD, BCPS; Monuteaux, Michael ScD; Sandora, Thomas J. MD, MPH* **; Patterson, Al PharmD; Harper, Marvin B. MD*†

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Abstract

Background:

Despite its frequent use, the optimal dosing regimen of intravenous vancomycin remains controversial. Achievement of therapeutic trough early in the course of illness may be beneficial. Our objective was to assess whether a loading dose of vancomycin would increase the proportion of children reaching target trough concentrations 8 hours after initiation of therapy.

Methods:

We enrolled hospitalized children aged 2–18 years prescribed vancomycin at Boston Children’s Hospital between February 2011 and January 2012. Participants were randomized to receive a loading dose (30 mg/kg) or a conventional initial dose (20 mg/kg). These were followed by a 20 mg/kg/dose every 8 hours in both groups. Serum vancomycin concentrations were measured before the second and third doses. Pharmacokinetic parameters were calculated using individual and population pharmacokinetic models.

Results:

Two of nineteen (11%) loading dose recipients had a trough 15–20 mg/L before the second dose, compared with 0 of 27 in the conventional dose group (P = 0.17). However, the median area under the curve/minimum inhibitory concentration estimates (for a hypothetical minimum inhibitory concentration = 1 mg/L) were above 400 in both groups. Red man syndrome incidence was higher in loading dose recipients (48% vs. 24%, P = 0.06).

Conclusions:

A vancomycin loading dose did not result in earlier achievement of therapeutic trough concentrations in this study. However, the systemic exposure to vancomycin in children administered 60 mg/kg/day was adequate, despite lower than recommended measured trough levels. Therefore, the need for higher target trough concentrations should be questioned.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Copyright © 2013 by Lippincott Williams & Wilkins

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