Clearance of linezolid via continuous venovenous hemodiafiltration.
BACKGROUND
Linezolid is being used increasingly for life-threatening vancomycin-resistant infections in critically ill patients. Limited data suggest that linezolid is cleared by intermittent hemodialysis. However, information on clearance of linezolid by continuous renal replacement therapy is limited. A patient undergoing continuous venovenous hemodiafiltration (CVVHDF) was evaluated to determine linezolid clearance through CVVHDF.


METHODS
A 33-year-old man with necrotizing fasciitis and acute-on-chronic renal failure requiring CVVHDF was treated with linezolid, 600 mg every 12 hours, for a vancomycin-resistant urinary tract infection. The study was performed on day 4 of therapy after a 1-hour infusion of linezolid. A series of blood samples and all urine and diafiltrate were collected during a 12-hour period. Linezolid concentrations were determined by using high-performance liquid chromatography assay. Linezolid clearance through CVVHDF was determined by using 2 methods. Method 1 evaluated the amount of drug recovered in diafiltrate. Method 2 evaluated plasma drug concentrations in prefilter and postfilter (PAN-10 Hemofilter; Asahi Medical Co, Tokyo, Japan) samples.


RESULTS
Clearance of linezolid through CVVHDF was 15.6 mL/min by method 1 and 21.6 mL/min by method 2. Total-body clearance was 189 mL/min. The amount of linezolid recovered in diafiltrate was 50 mg (8.3% of the dose).


CONCLUSIONS
Clearance of linezolid through CVVHDF in this patient was marginal. It does not appear that supplemental dosing of linezolid is necessary in patients undergoing CVVHDF.
Mauro
Laurie S
LS
University of Toledo College of Pharmacy, OH, USA. lmauro@utnet.utoledo.edu
Peloquin
Charles A
CA
Schmude
Kimberly
K
Assaly
Ragheb
R
Malhotra
Deepak
D
D000081:Acetamides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D058186:Acute Kidney Injury / Q000097:blood / Q000628:therapy / Q000652:urine; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D024881:Drug Resistance, Bacterial; D019115:Fasciitis, Necrotizing / Q000097:blood / Q000628:therapy / Q000652:urine; D006440:Hemofiltration / Q000379:methods*; D006801:Humans; D000069349:Linezolid; D008297:Male; D008657:Metabolic Clearance Rate; D023303:Oxazolidinones / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D013997:Time Factors; D014552:Urinary Tract Infections / Q000097:blood / Q000188:drug therapy / Q000652:urine; D014640:Vancomycin / Q000627:therapeutic use
D000081:Acetamides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid