Linezolid extracorporeal removal during haemodialysis with high cut-off membrane in critically ill patients

• A dialysate saturation coefficient ranging from 0.66–0.85 was observed for linezolid during HCO-CVVHD.
• Extracorporeal clearance from 2.1–2.5 L/h was observed for linezolid during HCO-CVVHD with a diffusive dose of 35 mL/kg/h.
• The high variability in linezolid PK/PD is more likely to be related to the patient's critical condition and/or organ dysfunction than to the ability of HCO-CVVHD in removing the drug.

Continuous venovenous haemodialysis with high cut-off membrane (HCO-CVVHD) is often used in critically ill septic patients with acute kidney injury (AKI) to sustain renal function and to remove circulating inflammatory mediators. The aim of this study was to analyse the extracorporeal removal of linezolid and related alterations in pharmacokinetic/pharmacodynamic (PK/PD) parameters during HCO-CVVHD. Three critically ill septic patients with AKI, treated with linezolid and HCO-CVVHD, were prospectively observed. To calculate the extracorporeal clearance of linezolid and the PK parameters, effluent, pre-filter and post-filter samples were contemporaneously collected before linezolid infusion, just after 1-h infusion (maximum serum concentration; Cmax), at 3 h and 6 h after dosing, and before the next dose (trough serum concentration; Cmin). Linezolid Cmax and Cmin (pre-filter) ranged from 10.4–23.5 mg/L and from 2.9–10.3 mg/L. The dialysate saturation coefficient was 0.66–0.85 and the extracorporeal clearance with a diffusive dose of 35 mL/kg/h ranged from 2.1–2.5 L/h. Total linezolid clearance was between 1.7 L/h and 6.3 L/h. The total area under the plasma concentration–time curve (AUC0–∞) ranged from 95.1 mg h/L to 352.9 mg h/L, in accordance with the different clinical conditions. AUCfree/MIC ratios were always <85 for an MIC of 4.0 mg/L, and two of three patients did not reach the optimal PK/PD target of ≥85 even when using an MIC of 2.0 mg/L. Although extracorporeal clearance may affect linezolid total clearance, the clinical features of critically ill septic patients appear to be mainly responsible for the high variability of linezolid serum concentrations.