Assessment of oXiris membrane adsorption towards Linezolid: implications for optimizing antibiotic therapy in critically ill patients

Background and Aims Sepsis in critically ill patients triggers dysregulated inflammation, leading to organs dysfunction. Antibiotic therapy is crucial in treatment, but faces challenges in optimal delivery due to potential loss in the effluent or adsorption on the sorbents surface. Linezolid (LZD), a common anti Gram-positive antimicrobial, with high volume of distribution, low protein binding (31%), may experience subtherapeutic levels during renal replacement therapies (RRT). This study aimed to evaluate LZD in vitro interaction with the membrane which the oXiris fibers are made of and its pharmacokinetic implications. Method The filter oXiris (Baxter, Deerfield, USA) features a membrane of polyacrylonitrile methalysulfonate coated with polyethyleneimine and unfractioned heparin used in septic patients. In order to test LZD removal via adsorption, the dialysate inlet and outlet were clamped. A customized circuit was assembled to circulate the tested solution inside the fibers and applied to the GALILEO testing platform, specifically developed for in vitro extracorporeal circulation (Fig. 1). 600 mL of tested solution (300 mL of saline solution and 600 mg/300 mL of LZD solution) were circulated through the filter at 120 mL/min for 120 minutes in a closed-loop configuration. Samples were collected at 0, 5, 10, 15, 20, 30, 60, 90 and 120 minutes from the reservoir. LZD concentrations were measured through ARK Linezolid Assay using ILab 650 (Werfen) instrument. LZD removal ratio (RR) and mass adsorption were assessed. Results In vitro circulation highlighted a mild affinity of oXiris to bind LZD. The membrane showed a rapid adsorption only in the first minutes of the test. LZD concentration in the reservoir significantly dropped within 5 minutes of circulation, from 0.92 mg/mL to 0.59 mg/mL. Indeed, the RR reached 36% and settled around that value for the remaining time (Fig. 2). Throughout the experiment, LZD mass adsorbed resulted 305.6mg (from 554.4 to 248.9mg). Conclusion This in vitro study underscores the potential risk of LZD subtherapeutic levels during RRT with oXiris, stressing the importance of optimizing antibiotic therapy in critically ill patients undergoing extracorporeal treatments. The implementation of therapeutic drug monitoring is essential to ensure sufficient antimicrobial dosing and enhance patient outcomes.