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). CONCLUSION: 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.
BACKGROUND:Linezolid is being used increasingly for life-threatening vancomycin-resistant infections in critically illpatients. 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). CONCLUSION: 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.
Authors: Antonello Di Paolo; Paolo Malacarne; Emanuele Guidotti; Romano Danesi; Mario Del Tacca Journal: Clin Pharmacokinet Date: 2010-07 Impact factor: 6.447
Authors: Stefanie Swoboda; Michael C Ober; Christoph Lichtenstern; Soundos Saleh; Vedat Schwenger; Hans-Günther Sonntag; Walter Emil Haefeli; Georg Hempel; Torsten Hoppe-Tichy; Markus A Weigand Journal: Eur J Clin Pharmacol Date: 2009-12-16 Impact factor: 2.953