Fiaccadori Enrico, Maggiore Umberto, Rotelli Carlo, Giacosa Roberto, Parenti Elisabetta, Picetti Edoardo, Manini Paola, Andreoli Roberta, Cabassi Aderville
Terapia Intensiva, Dipartimento di Clinica Medica, Nefrologia & Scienze della Prevenzione, Università degli Studi di Parma, Via Gramsci 14-43100 Parma, Italy.
Nephrol Dial Transplant. 2006 May;21(5):1402-6. doi: 10.1093/ndt/gfl048. Epub 2006 Feb 27.
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.
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.
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.
HD can significantly reduce serum linezolid levels in critically ill patients with renal failure.
既往研究表明，单次血液透析（HD）治疗可清除约三分之一的利奈唑胺给药剂量，但对于接受间歇性HD治疗的重症肾衰竭患者，这种清除是否会对血清抗生素浓度产生不利影响尚不清楚。
5例患有脓毒症且接受血液透析治疗的重症男性患者（平均年龄75岁，范围68 - 82岁；急性生理学与慢性健康状况评分系统II [APACHE II]评分为26.4，范围23 - 29；5例患者中2例存活），静脉注射利奈唑胺，每12小时600mg。采用高效液相色谱/质谱法测定血清抗生素水平。当在利奈唑胺输注后进行HD治疗时，我们将谷浓度分类为“有HD”，否则分类为“无HD”。我们还在患者透析时和非透析时计算群体药代动力学。
在36天的抗生素治疗期间，共获得222个血清利奈唑胺浓度数据，在此期间患者接受了31次HD治疗。血清利奈唑胺谷浓度平均为5.83mg/L（范围1.48 - 15.84），68.9%的样本超过4.0mg/L；然而，“有HD”时的谷浓度低于“无HD”时的谷浓度（4.68mg/L [范围1.48 - 9.07] 对 6.74mg/L [范围2.04 - 15.84]，P<0.001）。透析时清除率和半衰期分别为6.0L/h和4.0小时，非透析时分别为4.4L/h和7.3小时。
HD可显著降低重症肾衰竭患者的血清利奈唑胺水平。
