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

Federico Pea, Pierluigi Viale, Manuela Lugano, Federica Pavan, Luigia Scudeller, Giorgio Della Rocca, Mario Furlanut

Research output: Contribution to journalArticle

Abstract

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 (C min >MIC 90) or of area under the plasma concentration time curve to MIC 90 ratio (AUC/MIC 90) >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-τ] 334.71 versus 109.34 mg/L·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.

Original languageEnglish
Pages (from-to)1097-1102
Number of pages6
JournalAmerican Journal of Kidney Diseases
Volume44
Issue number6
DOIs
Publication statusPublished - Dec 2004

Keywords

  • linezolid
  • Pharmacokinetics, continuous venovenous hemofiltration (CVVH)
  • sieving coefficient

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Linezolid disposition after standard dosages in critically ill patients undergoing continuous venovenous hemofiltration: A report of 2 cases'. Together they form a unique fingerprint.

  • Cite this