Monte Carlo simulation to optimize polymyxin B dosing regimens for the treatment of Gram-negative bacteremia

2025

Frontiers in Cellular and Infection Microbiology, Vol 15 (2025)

ObjectiveThis study aimed to predict and evaluate the efficacy of various polymyxin B dosing regimens for Gram-negative bacteremia using Monte Carlo simulation, with a specific focus on assessing the efficacy in patients receiving continuous renal replacement therapy (CRRT). The goal was to optimize clinical dosing regimens and guide rational polymyxin B use in practice.MethodsA total of 1,939 Gram-negative bacterial strains were analyzed, collected between April 2019 and December 2021 through the China Bloodstream Gram-negative Pathogens Antimicrobial Resistance and Virulence Surveillance Network (CARVIS-NET). Pharmacokinetic parameters of polymyxin B from existing literature were used to conduct a Monte Carlo simulation based on pharmacokinetic/pharmacodynamic (PK/PD) theory. The probability of target attainment (PTA) and cumulative fraction of response (CFR) were evaluated across various dosing regimens.ResultsThe main pathogens of Gram-negative bacteremia were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, all of which demonstrated high susceptibility to polymyxin B. For pathogens with a minimum inhibitory concentration (MIC) ≤1 mg/L, all regimens achieved PTA >90%. However, when the MIC increased to 2 mg/L, the PTA for the 500,000 IU q12h regimen decreased to 77.53%, and at an MIC of 4 mg/L, none of the dosing regimens achieved a PTA >90%. For P. aeruginosa and K. pneumoniae with MIC ≤0.5 mg/L, all regimens demonstrated effectiveness. However, at MIC ≥1 mg/L, significant declines in PTA were observed, with the 500,000 IU q12h and 1.25 mg/kg q12h regimens yielding suboptimal outcomes. In CRRT patients, PTA values declined further, particularly against K. pneumoniae, raising concerns about potential treatment failure.ConclusionPolymyxin B demonstrates high efficacy for Gram-negative bacteremia with MIC ≤1 mg/L. However, efficacy diminishes as MIC increases, particularly for P. aeruginosa and K. pneumoniae, where 500,000 IU q12h and 1.25 mg/kg q12h regimens may result in suboptimal outcomes. For CRRT patients with K. pneumoniae bacteremia, therapeutic drug monitoring and dose adjustments are crucial to mitigate treatment failure risks.

article

English

Frontiers Media S.A., 2025.

polymyxin B, Monte Carlo simulation, Gram-negative bacteria, bacteremia, pharmacokinetics/pharmacodynamics (PK/PD), Microbiology, QR1-502