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Vancomycin loading dose and AUC0-24 target attainment in pediatric sepsis: a single-center randomized controlled
Kritsaporn Sujjavorakul1,2, Stephen J Kerr3,4,5, Noppadol Wacharachaisurapol6,7
1Division of Pediatric Critical Care, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Insights
A vancomycin loading dose in pediatric sepsis patients reduced underdosing and improved steady-state target attainment without increasing adverse events. This strategy is important for optimizing vancomycin therapy, especially in patients with augmented renal clearance.
Area of Science:
- Pediatric critical care medicine
- Pharmacology and pharmacokinetics
- Infectious diseases
Background:
- Achieving target vancomycin exposures is critical for treating pediatric sepsis.
- Altered pharmacokinetics in critically ill children complicate vancomycin dosing.
- Optimizing vancomycin therapy is essential for effective treatment outcomes.
Purpose of the Study:
- To investigate if a vancomycin loading dose improves target attainment of the area under the concentration curve in the first 24 hours (AUC₀₋₂₄) in pediatric sepsis patients.
- To evaluate the impact of a loading dose on reducing vancomycin underdosing and overdosing.
- To assess the safety and efficacy of vancomycin loading doses in this population.
Main Methods:
- Single-center, open-label, randomized controlled trial involving pediatric sepsis patients (3 months - 18 years).
- Patients randomized 2:1 to receive either a vancomycin loading dose or a standard dose.
- Primary outcome: achieving target AUC₀₋₂₄ (400-800 mg·h/L); secondary outcomes: serious adverse events and factors influencing target attainment.
Main Results:
- Overall target AUC₀₋₂₄ attainment did not differ significantly between groups.
- The loading dose significantly reduced AUC₀₋₂₄ underdosing (AUC < 400 mg·h/L).
- Loading dose improved steady-state target attainment; no significant differences in 90-day mortality or acute kidney injury were observed.
Conclusions:
- Vancomycin loading doses reduce underdosing and improve steady-state target achievement in pediatric sepsis patients.
- This strategy can be incorporated into vancomycin therapy, particularly for patients with augmented renal clearance.
- Optimized vancomycin dosing is crucial, and loading doses offer a viable approach without increased adverse events.
Background:
Achieving target vancomycin exposures is crucial for treating pediatric sepsis but is complicated by altered pharmacokinetics in critically ill children. This study investigated whether a loading dose improve target attainment of the area under the concentration curve in the first 24 h (AUC0-24).
Methods:
This single-center, open-label, randomized controlled trial enrolled pediatric sepsis patients (3 months - 18 years) at King Chulalongkorn Memorial Hospital, Thailand. Patients were randomized 2:1 to receive a vancomycin loading dose or a standard dose. The primary outcome was achieving target AUC0-24 (400-800 mg·h/L). An AUC0-24 < 400 mg·h/L was defined as underdosing and >800 mg·h/L as overdosing. Secondary outcomes included serious adverse events and factors influencing target attainment.
Results:
Of 78 participants (loading dose n = 51; standard dose n = 27), overall target AUC₀₋₂₄ attainment did not differ significantly. However, the loading dose reduced AUC0-24 underdosing and improved steady-state target attainment. No significant differences in 90-day mortality or acute kidney injury were observed. Estimated glomerular filtration rate and receiving the loading dose were associated with achieving a therapeutic AUC₀₋₂₄.
Conclusion:
Although a loading dose did not increase overall target AUC₀₋₂₄ attainment, it reduced AUC0-24 underdosing and improved steady-state target achievement without additional adverse events.
Impact:
This randomized controlled trial showed that vancomycin loading doses in pediatric sepsis patients significantly reduced the proportion of patients with area under the concentration curve (AUC) in the first 24 h that were underdosing compared to the standard dose. The loading dose also improved target attainment of AUC over 24 h at steady-state levels, without increasing the risk of serious adverse events. This study highlights the importance of optimizing vancomycin dosing, particularly in patients with augmented renal clearance. These findings support incorporating a loading dose strategy into vancomycin therapy for pediatric sepsis patients, especially those with augmented renal clearance.
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