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Published on: September 9, 2015
A randomized controlled trial of a vancomycin loading dose in children
Alicia Demirjian1, Yaron Finkelstein, Alejandro Nava-Ocampo
1From the *Department of Medicine, Division of Infectious Diseases; †Clinical Pharmacology Research Program, Division of Emergency Medicine, Boston Children's Hospital, Boston, MA; ‡Division of Emergency Medicine; §Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children; ¶Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; ‖Department of Pharmacy; and **Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA.
Insights
A vancomycin loading dose did not improve early therapeutic trough concentrations in children. Systemic exposure was adequate, suggesting current target trough levels may need reevaluation for optimal vancomycin therapy.
Area of Science:
- Pediatric pharmacology
- Infectious disease pharmacotherapy
- Clinical pharmacokinetics
Background:
- Optimal intravenous vancomycin dosing remains debated.
- Early achievement of therapeutic trough concentrations is considered beneficial.
- This study investigated the impact of a vancomycin loading dose in children.
Purpose of the Study:
- To determine if a vancomycin loading dose increases the proportion of children achieving target trough concentrations 8 hours after therapy initiation.
- To assess the pharmacokinetic profile of vancomycin with and without a loading dose in pediatric patients.
Main Methods:
- Randomized controlled trial in hospitalized children aged 2-18 years.
- Comparison of a 30 mg/kg loading dose versus a 20 mg/kg conventional initial dose.
- Serum vancomycin concentrations measured pre-dose; pharmacokinetic parameters calculated.
Main Results:
- No significant difference in achieving target trough concentrations (15-20 mg/L) by the second dose (11% vs. 0%, P=0.17).
- Adequate systemic exposure (AUC/MIC > 400) in both groups.
- Higher incidence of Red Man Syndrome in the loading dose group (48% vs. 24%, P=0.06).
Conclusions:
- A vancomycin loading dose did not facilitate earlier achievement of therapeutic trough levels in this pediatric cohort.
- Vancomycin systemic exposure was sufficient with standard daily doses, even with lower measured troughs.
- The necessity of current high target trough concentrations for vancomycin in children warrants further investigation.
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.
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