Vancomycin loading dose and AUC_0-24 target attainment in pediatric sepsis: a single-center randomized controlled...

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 (AUC_0-24).

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 AUC_0-24 (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.

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 AUC_0-24 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.

Although a loading dose did not increase overall target AUC₀₋₂₄ attainment, it reduced AUC_0-24 underdosing and improved steady-state target achievement without additional adverse events.

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.