Polymyxin B (PMB) and polymyxin E - colistin (COL) are representatives of the currently used cyclic peptide antibiotics. Introduced into medical practice in the 1950s, they have had limited use due to severe nephro- and neurotoxicity and a narrow therapeutic range. However, due to the expansion of antibiotic-resistant forms of microorganisms, PMB and COL, which have retained their effectiveness against gram-negative pathogens, have become extremely in demand in emergency medicine as ‘last line’ drugs. In critically ill patients, the clearance and distribution of drugs changes significantly; therefore, the concentration of antibiotics in the blood and the site of infection becomes suboptimal, and therapy is ineffective. Frequent damage to kidney function leads to decreased antibiotic clearance and an increased risk of toxicity. The use of extracorporeal techniques [renal replacement therapy, plasmapheresis, hemodialysis, extracorporeal membrane oxygenation (ECMO)] also often significantly modifies the classical pharmacokinetics of drugs, and their dosage regimen requires additional correction. Therefore, rational prescribing of antibacterial drugs in this category of patients requires a personalized approach, which involves monitoring the concentration of drugs in the biofluids of patients in critical condition. To study the pharmacokinetics of PMB in different categories of patients, several formats of competitive enzyme-linked immunosorbent assay (ELISA) have been developed. Antibodies obtained against the BSA-PMB conjugate and the immunoassay created on their basis made it possible to recognize both polymyxins - PMB (100%) and COL (88-95%)¹. The direct ELISA format with antibodies adsorbed on plates was preferable due to its short duration (1.5 h) and good correlation with HPLC-MS/MS (R²=98%). The linear measurement range was 5.0–192 ng/mL, which made it possible to analyze serum samples after a simple 100-fold dilution of PBS and determine the content of total PMB². Free drug, not bound to plasma proteins, was measured after equilibrium dialysis³. A comparative study conducted in critically ill patients on ECMO (n=13) and without ECMO support (n=21) revealed a number of features of the pharmacokinetics of PMB and higher exposure to PMB in patients on ECMO compared to the control group⁴. Drug monitoring of patients with renal failure (n=13) revealed decreased clearance of PMB, putting them at risk for toxicity. For patients with anuria who require continuous venovenous hemodialysis, it is recommended to change the dosage of the drug⁵.

Acknowledgements:
We thank all Clinical Hospital #1 MEDSI ICU staff for their help with sample and data collection.

Conflicts of Interest:
The authors declare that they have no conflict of interest in the publication of this article. The authors have no conflicts of interest to report in this work. Abstract was not submitted elsewhere and was first published here.

Funding:
This research received no external funding from any funding agency in the public, commercial, or not-for-profit sectors.