Vancomycin Dosing Regimens based on Monte Carlo Simulation for Treated Gram-positive cocci Infection in neonates: A retrospective observational study

Abstract Background: The pharmacodynamic and pharmacokinetic profiles of vancomycin in neonatal population have been previously reported. However, a consensus still has not been reached about optimal recommended dose. Few studies on neonatal population are available relating particularly to distribution of pathogens and clinical outcome.Therefore, we sought to optimise the drug-dosing regimen based on Monte Carlo Simulation and conducted a retrospective observational study to assess the trough concentration and clinical efficacy. Methods: We collected data from neonates who were treated with vancomycin from November 2018 to December 2021. Based on the inclusion criteria, pharmacokinetic model group and observation group were selected for further inclusion. The recommended pharmacokinetic-pharmacodynamic(PK-PD) target AUC/MIC ratio for vancomycin is ≥400. The achieved goal of the probability of target attainment (PTA) and a cumulative fraction of response (CFR) were ≥90%. Monte-Carlo simulations were performed to identify optimal dosing regimens. Statistical analysis were performed to compare trough concentrations and effectiveness of the different treatment options. Results: We collected pharmacokinetic data on a total of 137 neonates ( 92 male and 45 female) and 124 neonates ( 180 dosing regimens and 180 plasma trough concentration) were retrospectively analyzed in this study. The recommended doses required to achieve the goal of PTA or CFR from 25 to 225mg/d depending on PK-PD target in different subgroups. Recommended dosage regimen group ( n=80 ) presented higher values (P＜0.05）in trough concentration than in not-recommended groups ( n=100 ), yet the target concentration ( 5-15mg/l ) compliance rate indicates no significant differences (P＞0.05). Recommended dosage neonate group ( n=53 ) presented higher clinical response rate (P＜0.05）than in not-recommended groups ( n=71 ). Conclusion: Large differences of required daily dose exist among different newborn subgroups. A higher trough level and clinical efficacy was reached in simulated recommended doses regimen. However target concentration compliance rate indicates no significant change. A more scientific and standard study of multi-center were needed to optimize recommended dose and evaluate the real-world efficacy and safety of vancomycin.