Quantification of Polymyxin E in Plasma and Epithelial Lining Fluid: Validation and Clinical Application

Polymyxin E (PME) is an essential "last-resort" antibiotic for multidrug-resistant Gram-negative infections, but its narrow therapeutic window and high pharmacokinetic variability necessitate therapeutic drug monitoring (TDM). In this study, we developed and validated a sensitive LC-MS/MS method for quantifying PME in plasma and epithelial lining fluid (ELF) from patients receiving colistin sulfate therapy. Plasma and bronchoalveolar lavage samples were processed by protein precipitation with a 1:1 mixture of 5 % aqueous trichloroacetic acid and acetonitrile and analyzed on a triple quadrupole mass spectrometer, with validation according to FDA/EMA guidelines. Retrospective analysis of plasma samples from 40 critically ill patients revealed that trough concentrations, but not peak levels, differed significantly between patients with and without acute kidney injury (median, 1.50 vs. 0.79 μg/mL, p = 0.021). No clear correlation with clinical efficacy was observed. In a prospective cohort, paired plasma and ELF data from four patients suggested that inhaled administration produced markedly higher ELF concentrations than plasma concentrations, providing the first clinical evidence of pulmonary drug exposure after colistin sulfate inhalation. Overall, this validated method is suitable for routine TDM of PME. The findings support future studies to evaluate plasma trough levels and ELF concentrations in guiding individualized therapy for critically ill patients.