Linezolid disposition after standard dosages in critically ill patients undergoing continuous venovenous hemofiltration: a report of 2 cases

Am J Kidney Dis. 2004 Dec;44(6):1097-102. doi: 10.1053/j.ajkd.2004.08.032.


Linezolid is a new oxazolidinone antibiotic active against most Gram-positive microorganisms the renal elimination of which accounts for about 30% to 35% of all the clearance. Its pharmacokinetic ability was assessed during continuous venovenous hemofiltration (CVVH) in 2 anuric patients with severe postsurgical intraabdominal infections who were receiving standard dosages (600 mg intravenously twice a day). Blood samples for quantification of linezolid in plasma and in filtrate were collected after more than 4 days of therapy before dosing and at 0, 0.5, 1, 2, 3, 5, 7, 9, and 11 hours after the morning 1-hour intravenous infusion, and concentrations were determined by means of high-performance liquid chromatography. Linezolid was partially cleared by CVVH in both the patients (hemofiltration clearance [CL CVVH ] = 0.38 and 0.35 mL/min/kg), with high sieving coefficient values (0.76 to 0.92). Efficacious plasma exposure for time-dependent antibacterial activity of linezolid, either in terms of trough levels above minimum inhibitory concentration (MIC) at which 90% of the isolates are inhibited (Cmin >MIC90 ) or of area under the plasma concentration time curve to MIC90 ratio (AUC/MIC90 ) >100 hours, was ensured during CVVH in both patients. However, despite similar CL CVVH , significant interindividual pharmacokinetic variability was found in the 2 patients (AUC during the observational period [AUC 0-tau ] 334.71 versus 109.34 mg/L x h), mainly owing to substantial differences in non-CVVH-related clearance of linezolid (total CL, 0.55 versus 1.21 mL/min/kg). Our findings indicate that linezolid, although partially removed, does not warrant dosage modification during the first 48 hours when CVVH (with polysulfide hemofilter) at standard 2,000 mL/h substitution flow rate in predilution is applied to anuric patients. Thereafter, this choice is a reasonable one with the exception of those patients who have other features of linezolid toxicity and in which non-CVVH-related clearance might be impaired, although further evaluations are warranted.

Publication types

  • Case Reports

MeSH terms

  • Acetamides / administration & dosage*
  • Acetamides / therapeutic use
  • Aged
  • Drug Administration Schedule
  • Gram-Positive Bacterial Infections / drug therapy
  • Hemofiltration / methods*
  • Humans
  • Infusions, Intravenous
  • Kidney Failure, Chronic / therapy
  • Linezolid
  • Male
  • Middle Aged
  • Oxazolidinones / administration & dosage*
  • Oxazolidinones / therapeutic use
  • Peritonitis / drug therapy
  • Surgical Wound Infection / drug therapy


  • Acetamides
  • Oxazolidinones
  • Linezolid