Population Pharmacokinetics of Vancomycin and Dose Optimization in Pediatric Patients with Sepsis or Septic Shock

Authors

Nuntapong Boonrit, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkla, Thailand; The College of Pharmacotherapy of Thailand, The Pharmacy Council of Thailand, Nonthaburi, Thailand
Thitima Wattanavijitkul, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
Preecha Montakantikul, The College of Pharmacotherapy of Thailand, The Pharmacy Council of Thailand, Nonthaburi, Thailand; Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
Kamolwish Laoprasopwattana, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
Sutthiporn Pattharachayakul, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkla, Thailand; The College of Pharmacotherapy of Thailand, The Pharmacy Council of Thailand, Nonthaburi, ThailandFollow

Abstract

Objectives: This study aimed to develop a population pharmacokinetic model for vancomycin in pediatric patients with sepsis or septic shock and to propose tailored initial dose recommendations based on the model’s findings. Methods: We conducted a retrospective analysis of pediatric patients with sepsis or septic shock who received vancomycin treatment from January 2017 to December 2019. A population pharmacokinetic model was developed using NONMEM. Monte Carlo Simulations were performed using Crystal Ball software to determine the probability of target attainment (PTA) for different vancomycin dosage regimens based on the target PK/PD index of AUC24hr/MIC > 400 Results: Analyzing 580 vancomycin concentrations from 228 patients (median age 4.1 years; 33.8% with septic shock), we determined that a one-compartment model best described the pharmacokinetics, estimating clearance (CL) at 1.8 L/hr and volume of distribution (Vd) at 15.8 L. Body weight (BW) significantly influenced both CL and Vd, while serum creatinine (SCr) and blood urea nitrogen (BUN) affected only CL. The optimal doses adjusted by SCr and BW to achieved PTA range from 60 mg/kg/day (SCr 0.1–0.3 mg/dL) decreasing to 20–30 mg/kg/day (SCr 0.7–1.0 mg/dL) when the MIC ≤ 0.5 mg/L. For MIC = 1 mg/L, higher doses up to 90 mg/kg/day are needed in patients with low SCr. A loading dose of 25–35 mg/kg was necessary to reach PTA within 24 hours. No regimen achieved target PTA at MIC > 1 mg/L. Conclusions: Customized vancomycin dosing based on BW and renal function may improve target AUC attainment for S. aureus in sepsis or septic shock children. Caution is warranted for MIC >1 mg/L or SCr >1 mg/dL due to limited data.

Recommended Citation

Boonrit, Nuntapong; Wattanavijitkul, Thitima; Montakantikul, Preecha; Laoprasopwattana, Kamolwish; and Pattharachayakul, Sutthiporn (2025) "Population Pharmacokinetics of Vancomycin and Dose Optimization in Pediatric Patients with Sepsis or Septic Shock," Journal of Pediatric Infectious Diseases: Vol. 20: Iss. 4, Article 6.
Available at: https://jpid.researchcommons.org/journal/vol20/iss4/6