Department of Nephrology and Hypertension, Medical School Hannover, Germany.
Nephrol Dial Transplant. 2010 May;25(5):1537-41. doi: 10.1093/ndt/gfp704. Epub 2009 Dec 22.
Daptomycin is a new intravenous cyclic lipopeptide antibiotic, licensed for the treatment of complicated skin and soft tissue infections caused by Gram-positive organisms including both susceptible and resistant strains of Staphylococcus aureus and for the treatment of various infections due to susceptible organisms, including serious and life-threatening Gram-positive infections, vancomycin-resistant enterococcal infections and right-sided endocarditis with associated bacteremia. Currently, no dosing recommendations exist for this drug for patients with acute kidney injury (AKI) undergoing renal replacement therapy. The aim of this study was to evaluate pharmacokinetics of daptomycin in critically ill patients with AKI undergoing extended dialysis (ED), a frequently used mean of renal replacement therapies in intensive care units (ICUs) around the world. Patients and methods. A prospective, single-dose pharmacokinetic study was performed in the medical and surgical ICUs of a tertiary care center. The aim was to investigate critically ill patients with anuric AKI being treated with ED and receiving daptomycin (n = 10). Daptomycin (6 mg/kg) was administered 8 h before ED was started.
Key pharmacokinetic parameters like half-life in critically ill patients treated with ED were comparable to healthy controls. The dialyser clearance for daptomycin was 63 +/- 9 ml/min. Based on the amount of the drug recovered from the collected spent dialysate, the mean fraction of the drug removed by one dialysis treatment was 23.3%.
Our data suggest that patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m(2); blood and dialysate flow, 160 ml/min; ED time, 480 min) and employing current dosing regimen, 6 mg/kg daptomycin every 48 h, run the risk of becoming significantly under dosed if one adheres to a twice daily dosing schedule that is recommended for patients on maintenance haemodialysis. Our data suggest that a daily dose of 6 mg/kg daptomycin is necessary in this special patient population to avoid under dosing, which may have detrimental effects in critically ill patients suffering from life-threatening infections.
达托霉素是一种新型的静脉内环肽抗生素，已获得许可用于治疗由革兰氏阳性菌引起的复杂性皮肤和软组织感染，包括对金黄色葡萄球菌敏感和耐药的菌株，以及治疗各种敏感菌引起的感染，包括严重和危及生命的革兰氏阳性感染、耐万古霉素肠球菌感染和右侧心内膜炎伴相关菌血症。目前，对于接受肾脏替代治疗的急性肾损伤（AKI）患者，尚无该药物的剂量推荐。本研究旨在评估在接受延长透析（ED）的 AKI 重症患者中的达托霉素药代动力学，ED 是世界各地重症监护病房（ICU）中常用的肾脏替代治疗方法。
患者和方法。在一家三级护理中心的内科和外科 ICU 进行了一项前瞻性、单次剂量药代动力学研究。目的是研究接受 ED 治疗且接受达托霉素（n = 10）的无尿性 AKI 重症患者。在 ED 开始前 8 小时给予达托霉素（6mg/kg）。
接受 ED 治疗的重症患者的关键药代动力学参数（如半衰期）与健康对照者相似。达托霉素的透析器清除率为 63 ± 9ml/min。基于从收集的废弃透析液中回收的药物量，单次透析治疗去除的药物平均分数为 23.3%。
我们的数据表明，使用高通量透析器（聚砜，1.3m2；血液和透析液流量，160ml/min；ED 时间，480min）并采用目前的给药方案（每 48 小时给予 6mg/kg 达托霉素）的 ED 治疗患者，如果遵循推荐用于维持性血液透析患者的每日两次给药方案，可能会面临明显的剂量不足风险。我们的数据表明，在这种特殊的患者人群中，每天给予 6mg/kg 达托霉素是必要的，以避免剂量不足，这可能会对患有危及生命感染的重症患者产生不利影响。
Zotero 插件