title: Linezolid extracorporeal removal during haemodialysis with high cut-off membrane in critically ill patients.
abstract: 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; C(max)), at 3 h and 6 h after dosing, and before the next dose (trough serum concentration; C(min)). Linezolid C(max) and C(min) (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 m L/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 mgh/L to 352.9 mgh/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.
authors: Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. Electronic address: gianlucavilla1@gmail.com.
authors: Gianluca
authors: G
authors: Villa
authors: Department of Health Sciences, Section of Pharmacology, University of Florence, Florence, Italy.
authors: Maria Iris
authors: MI
authors: Cassetta
authors: Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Lorenzo
authors: L
authors: Tofani
authors: Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors: Serafina
authors: S
authors: Valente
authors: Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Cosimo
authors: C
authors: Chelazzi
authors: Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Silvia
authors: S
authors: Falsini
authors: Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Angelo Raffaele
authors: AR
authors: De Gaudio
authors: Department of Health Sciences, Section of Pharmacology, University of Florence, Florence, Italy.
authors: Andrea
authors: A
authors: Novelli
authors: Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, and International Renal Research Institute of Vicenza (IRRIV), Vicenza, Italy.
authors: Claudio
authors: C
authors: Ronco
authors: Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Chiara
authors: C
authors: Adembri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D016638:Critical Illness; D006801:Humans; D000069349:Linezolid / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*; D051437:Renal Insufficiency / Q000139:chemically induced*; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D000069349:Linezolid
keywords: High cut-off membrane; High-performance liquid chromatography; Linezolid; Pharmacodynamics; Pharmacokinetics; Sepsis