Continuous versus intermittent vancomycin infusions in critically ill children with gram-positive bacterial infections: a randomized controlled trial

OBJECTIVE: This randomized controlled trial (RCT) compares continuous intravenous infusion (CIV) and intermittent infusion of vancomycin (IIV) regimens (40 mg/kg/day) in PICU patients with Gram-positive infections. The study aims to evaluate pharmacokinetics/pharmacodynamics (PK/PD) target attainment (Area under curve/Minimum inhibitory concentration, AUC/MIC ≥ 400) and renal safety profiles, with the ultimate goal of establishing optimized dosing protocols to enhance first-dose attainment of steady-state concentrations and enhance AUC/MIC ratio compliance, thereby supporting individualized treatment strategies for critically ill children. METHODS: This single-center RCT was conducted at the PICU of Capital Center for Children’s Health, Capital Medical University (a tertiary pediatric critical care center specializing in severe infections in critically ill children) from June 2017 to June 2020. Eighty children (1 month to 14 years) with suspected or confirmed Gram-positive infections requiring vancomycin were randomized 1:1 to CIV (n = 40; 24-hour continuous infusion) or IIV (n = 40; intermittent infusion every 6 h, 1-hour infusion each time). PK/PD parameters (AUC0–24 h/MIC), clinical outcomes, and renal adverse events were compared. RESULTS: CIV achieved higher steady-state vancomycin concentrations than IIV (15.22 mg/L vs. 6.25 mg/L, p < 0.05). AUC0–24 h/MIC values were numerically higher in CIV (median 456.5 [Interquartile Range, IQR 291.9-590.9]) versus IIV (median 358.0 [IQR 276.1-714.4]), though differences were non-significant (p > 0.05).Between-group differences in clinical efficacy, including fever resolution and inflammatory markers, were not observed (p > 0.05). CONCLUSION: CIV rapidly achieves target vancomycin exposure in critically ill children without dose escalation, demonstrating comparable efficacy and renal safety to IIV. This strategy may optimize antimicrobial therapy in pediatric sepsis. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry (ChiCTR) on 24 February 2021 with the registration number ChiCTR2100043659