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Polymyxin B Intravenous Administration Strategy Guided by Minimum Inhibitory Concentration in Critically Ill Patients

Shengnan Zhang1, Nan Yang1, Ruwei Yang1

  • 1Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, China.

CPT: Pharmacometrics & Systems Pharmacology
|June 19, 2026
PubMed

Insights

This study optimizes intravenous polymyxin B (PMB) dosing for severe pulmonary infections using physiologically based pharmacokinetic (PBPK) models. It identifies effective regimens and targets for critically ill patients, improving treatment outcomes for drug-resistant gram-negative pneumonia.

Area of Science:

  • Pharmacology and Pharmaceutical Sciences
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Intravenous polymyxin B (PMB) is crucial for treating multidrug-resistant gram-negative bacterial infections.
  • However, its efficacy in pulmonary infections is often limited due to suboptimal dosing and penetration into lung tissues.
  • Identifying appropriate patient populations and optimal dosing strategies is essential for maximizing therapeutic benefit.

Purpose of the Study:

  • To identify critically ill patients suitable for monotherapy with intravenous PMB for severe pulmonary infections.
  • To recommend individualized optimal dosing regimens for intravenous PMB based on pharmacokinetic/pharmacodynamic (PK/PD) targets.
  • To evaluate the PK/PD targets and their correlation with clinical outcomes.

Main Methods:

  • Development and validation of physiologically based pharmacokinetic (PBPK) models using data from preclinical and clinical studies.
  • Prediction of PMB concentrations in epithelial lining fluid (ELF) and plasma.
  • Monte Carlo simulations to assess various dosing regimens against established PK/PD targets (ELF AUCss,24h/MIC ≥ 50).

Main Results:

  • Simulations indicated that specific intravenous PMB regimens (e.g., 100 mg or 1.50 mg/kg q12h) achieved the ELF PK/PD target in over 90% of patients for pathogens with MIC of 1 mg/L.
  • A plasma AUCss,24h/MIC threshold of 80.6 was identified, with retrospective analysis showing significantly better outcomes for patients exceeding this level (p=0.038).
  • Dosing recommendations varied based on pathogen MIC, suggesting 50 mg q12h for MICs ≤ 0.5 mg/L and adjunctive therapies for MICs ≥ 2 mg/L.

Conclusions:

  • PBPK modeling supports 100 mg or 1.50 mg/kg q12h as initial intravenous PMB regimens for critically ill patients with pulmonary infections.
  • Individualized dosing adjustments based on MIC and plasma exposure (AUCss,24h/MIC > 80.6) are recommended.
  • Therapeutic drug monitoring and consideration of adjunctive nebulization or combination therapy are advised for optimizing treatment outcomes.
Keywords:
PK/PDintravenous administrationminimum inhibitory concentrationphysiologically based pharmacokinetic modelingpolymyxin Bpulmonary infection

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