Pharmacokinetics and pharmacodynamics of polymyxin B and proposed dosing regimens in elderly patients with multi-drug-resistant Gram-negative bacterial infections

Elderly patients with multi-drug-resistant Gram-negative infections have limited pharmacokinetic and pharmacodynamic (PK/PD) data available to guide polymyxin B dosing. This study developed a population pharmacokinetic model in critically ill elderly patients (age 65+) receiving intravenous polymyxin B, using Phoenix NLME software and Monte Carlo simulations to propose optimized dosing regimens. Albumin was a significant covariate but had only a slight effect on exposure, and simulations indicated fixed doses of 50 mg or 75 mg would achieve PK/PD targets for susceptible pathogens (MIC ≤0.5 mg/L), while weight-based regimens might result in excessive exposure for lighter patients. The findings support fixed maintenance dosing regimens of 50-75 mg polymyxin B to balance efficacy and nephrotoxicity risk in elderly patients.