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Vancomycin AUC/MIC and Corresponding Troughs in a Pediatric Population
Insights
Vancomycin dosing in children for MRSA infections is challenging. A 15 mg/kg dose every 6 hours has a variable probability of achieving the target AUC/MIC > 400, correlating to a trough of 11 mg/L.
Area of Science:
- Pediatric Infectious Diseases
- Pharmacokinetics and Pharmacodynamics
- Antimicrobial Stewardship
Background:
- Adult guidelines recommend vancomycin AUC/MIC > 400 for MRSA, corresponding to trough concentrations of 15-20 mg/L.
- Achieving target vancomycin troughs in pediatric patients is clinically challenging.
- Pediatric vancomycin dosing requires specific pharmacokinetic evaluation.
Purpose of the Study:
- To assess the likelihood of achieving an AUC/MIC > 400 with vancomycin 15 mg/kg every 6 hours in pediatric patients.
- To determine the correlation between vancomycin trough concentrations and AUC/MIC targets in children.
- To evaluate the impact of different pharmacokinetic methods on AUC/MIC calculations.
Main Methods:
- Retrospective chart review of pediatric patients (>2 months to <18 years) with S. aureus bacteremia.
- Patients were grouped based on initial vancomycin dosing (≥15 mg/kg q6h vs. other).
- Area under the curve (AUC) was calculated using three pharmacokinetic methods; trapezoidal equation (Method A) was analyzed for correlation.
Main Results:
- Fifty-five patients received vancomycin ≥15 mg/kg q6h, with 99 trough concentrations assessed.
- The probability of achieving AUC/MIC > 400 varied widely (16.4%–90.9%) with a median trough of 11.4 mg/L in the higher dose group.
- An AUC/MIC of 400 correlated to a trough concentration of 11 mg/L using the trapezoidal method.
Conclusions:
- Vancomycin dosing of 15 mg/kg every 6 hours in children yields variable AUC/MIC > 400 achievement.
- The AUC/MIC target of 400 in pediatric patients correlates to a trough concentration of 11 mg/L when using the trapezoidal method.
- Pharmacokinetic method choice significantly impacts AUC/MIC calculations and target attainment assessment in pediatric vancomycin therapy.
Objectives:
Adult guidelines suggest an area under the curve/minimum inhibitory concentration (AUC/MIC) > 400 corresponds to a vancomycin trough serum concentration of 15 to 20 mg/L for methicillin-resistant Staphylococcus aureus infections, but obtaining these troughs in children are difficult. The primary objective of this study was to assess the likelihood that 15 mg/kg of vancomycin every 6 hours in a child achieves an AUC/MIC > 400.
Methods:
This retrospective chart review included pediatric patients >2 months to <18 years with a positive S aureus blood culture and documented MIC who received at least two doses of vancomycin with corresponding trough. Patients were divided into two groups: group 1 initially receiving ≥15 mg/kg every 6 hours, and group 2 initially receiving any other dosing ranges or intervals. AUCs were calculated four times using three pharmacokinetic methods.
Results:
A total of 36 patients with 99 vancomycin trough serum concentrations were assessed. Baseline characteristics were similar between groups. For troughs in group 1 (n = 55), the probability of achieving an AUC/MIC > 400 ranged from 16.4% to 90.9% with a median trough concentration of 11.4 mg/L, while in group 2 (n = 44) the probability of achieving AUC/MIC > 400 ranged from 15.9% to 54.5% with mean trough concentration of 9.2 mg/L. The AUC/MICs were not similar between the different pharmacokinetic methods used; however, a trapezoidal equation (Method A) yielded the highest correlation coefficient (r2 = 0.59). When dosing every 6 hours, an AUC/MIC of 400 correlated to a trough serum concentration of 11 mg/L.
Conclusions:
The probability of achieving an AUC/MIC > 400 using only a trough serum concentration and an MIC with patients receiving 15 mg/kg every 6 hours is variable based on the method used to calculate the AUC. An AUC/MIC of 400 in children correlated to a trough concentration of 11 mg/L using a trapezoidal Method to calculate AUC.
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