Does haemodialysis significantly affect serum linezolid concentrations in critically ill patients with renal failure? A pilot investigation

Abstract

Background: Previous studies have shown that a single haemodialysis (HD) session removes about one-third of the linezolid dose administered, but it is unknown whether in critically ill patients with renal failure on intermittent HD, this removal adversely affects serum antibiotic concentrations.

Methods: Five male critically ill patients (mean age 75 years, range 68-82; APACHE II score 26.4, range 23-29; survival 2/5) with sepsis and renal failure on haemodialysis, were administered i.v. linezolid, 600 mg every 12 h. Serum antibiotic levels were measured by high-performance liquid chromatography/mass spectrometry. We classified trough concentrations as 'with HD' when a HD session was performed after linezolid infusion, and 'without HD' otherwise. We also computed population pharmacokinetics while patients were on-dialysis and off-dialysis.

Results: A total of 222 serum linezolid concentrations were available over 36 days of antibiotic therapy, during which patients underwent 31 HD sessions. Trough serum linezolid levels averaged 5.83 mg/l (range 1.48-15.84), exceeding 4.0 mg/l in 68.9% of the samples; however, the trough levels 'with HD' were lower than those 'without HD' (4.68 mg/l [range 1.48-9.07] vs 6.74 mg/l [range 2.04-15.84], P<0.001). Clearance and half-life were 6.0 l/h and 4.0 h, respectively, while patients were on-dialysis, and 4.4 l/h and 7.3 h, respectively, when they were off-dialysis.

Conclusions: HD can significantly reduce serum linezolid levels in critically ill patients with renal failure.