Pharmacokinetics of linezolid in critically ill patients undergoing continuous venovenous hemofiltration

Background

Linezolid is a new antibacterial agent with a broad spectrum of activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE) and penicillin-resistant Streptococcus pneumoniae. The aim of this study was to determine the pharmacokinetic characteristics of linezolid in critically ill patients undergoing continuous venovenous hemofiltration (CVVH).

Methods

Twenty patients received linezolid (600 mg intravensouly every 12 hours). CVVH was performed using highly permeable polysulfone membranes (PSHF 1200, Baxter, Germany and AV 400, Fresenius, Germany). The mean blood flow rate and ultrafiltration rate were 182 ± 15 ml/min and 40 ± 8 ml/min, respectively. Postdilution was performed. Linezolid concentrations in serum and ultrafiltrate were determined by high-performance liquid chromatography.

Results

The mean linezolid serum concentration peak (Cmax) was 15.32 ± 3.98 μg/ml, and the mean trough level (Cmin) was 1.87 ± 1.70 μg/ml. The elimination half-life (T1/2) was 4.30 ± 1.74 hours. The total clearance (CLtot), hemofiltration clearance (CLhf) and volume of distribution (Vd) were 9.31 ± 3.48 l/hours, 31.25 ± 12.77 ml/min and 51.30 ± 12.30 l, respectively.

Conclusion

Our results indicate that patients with severe Gram-positive infections undergoing CVVH can be treated effectively with a dose of 600 mg linezolid every 12 hours.