Multiple-dose pharmacokinetics of linezolid during continuous venovenous haemofiltration

Abstract

Objectives: Linezolid is a new antibacterial agent with a broad spectrum of activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., and penicillin-resistant Streptococcus pneumoniae. The aim of this prospective, single-centre, open-label, two-arm study was to investigate the pharmacokinetics of linezolid during continuous venovenous haemofiltration (CVVH) in critically ill patients and to derive a dosage recommendation.

Patients and methods: Twenty anuric ICU patients undergoing CVVH (mean age and body weight 60.7 +/- 10.9 years and 86.0 +/- 18.0 kg) were included. All patients received linezolid 600 mg intravenously every 12 h. CVVH was performed using highly permeable polysulphone membranes (PSHF 1200, Baxter, Germany and AV 400, Fresenius, Germany). Mean blood flow rate and ultrafiltration rate were 186 +/- 15 and 40 +/- 8 mL/min, respectively. Post-dilution was performed.

Results: The pharmacokinetics of linezolid in critically ill patients with acute renal failure undergoing CVVH were comparable to healthy subjects and patients without renal impairment. The elimination half-life, total clearance and haemofiltration clearance were 4.3 +/- 1.7 h, 9.3 +/- 3.5 L/h and 1.9 +/- 0.8 L/h, respectively.

Conclusions: Our results showed that linezolid was highly removable by CVVH. These data suggest that a schedule of 600 mg linezolid at least twice daily may also be an appropriate dosing for patients with severe Gram-positive infections undergoing CVVH with both types of membranes.