Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure

OBJECTIVE: To study the removal of linezolid, a new oxazolidinone antibiotic, by renal replacement therapy in patients with acute renal failure. DESIGN: Prospective, single-dose pharmacokinetic study. SETTING: Renal intensive care unit of a tertiary university hospital. PATIENTS: Fifteen critically ill patients with oliguric acute renal failure on renal replacement therapy (seven males, mean age 72.3 yrs, range 60-94; Acute Physiology and Chronic Health Evaluation II score 24.9, range 18-36; mechanical ventilation ten of 15). INTERVENTIONS: All patients received 600 mg of intravenous linezolid before starting renal replacement therapy, which consisted of intermittent hemodialysis lasting 3-4 hrs in eight patients, sustained low-efficiency dialysis lasting 8 hrs in five patients, and continuous venovenous hemofiltration lasting 10.5-12 hrs in two patients. MEASUREMENTS AND MAIN RESULTS: Linezolid concentrations were measured by liquid chromatography/mass spectrometry methods on serum and dialysate/ultrafiltrate samples. At the start of renal replacement therapy, serum levels averaged 11.91 mg/L (range 5.49-21.52) and dropped at the end to levels <4 mg/dL (90% minimum inhibitory concentration values for Staphylococcus aureus) in three of eight patients on hemodialysis, three of five patients on sustained low-efficiency dialysis, and two of two patients on continuous venovenous hemofiltration. Mean removal of the drug was 193.7 mg with hemodialysis (32.3% of the dose administered), 205 mg with sustained low-efficiency dialysis (33.9%), and 74.8 mg (12.4%) and 105 (17.5%) mg following a continuous venovenous hemofiltration session lasting 10.5 and 12 hrs, respectively. CONCLUSIONS: In patients with acute renal failure, serum levels of linezolid can be reduced to the subtherapeutic range following renal replacement therapy.