Does haemodialysis significantly affect serum linezolid concentrations in critically ill patients with renal failure? A pilot investigation.
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.
Fiaccadori
Enrico
E
Terapia Intensiva, Dipartimento di Clinica Medica, Nefrologia & Scienze della Prevenzione, Università degli Studi di Parma, Via Gramsci 14-43100 Parma, Italy. enrico.fiaccadori@unipr.it
Maggiore
Umberto
U
Rotelli
Carlo
C
Giacosa
Roberto
R
Parenti
Elisabetta
E
Picetti
Edoardo
E
Manini
Paola
P
Andreoli
Roberta
R
Cabassi
Aderville
A
D018806:APACHE; D000081:Acetamides / Q000008:administration & dosage* / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood; D003422:Critical Care; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000628:therapy*; D007677:Kidney Function Tests; D000069349:Linezolid; D008297:Male; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000097:blood*; D010865:Pilot Projects; D006435:Renal Dialysis / Q000379:methods*; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid