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[多粘菌素:综述]

[Colistin: a review].

作者信息

Antonucci Elio, Taccone Fabio Silvio, Regolisti Giuseppe, Cabassi Aderville, Morabito Santo, Pistolesi Valentina, Di Motta Tommaso, Fiaccadori Enrico

出版信息

G Ital Nefrol. 2014 Nov-Dec;31(6).

Abstract

Colistin (CS) is a polymyxin with bactericidal activity, which is increasingly used in nosocomial infections associated with multidrug-resistant Gram-negative bacteria (MDR-GNB). Intravenous CS is usually administered as a less toxic pro-drug, i.e. colistin sodium methanesulfonate (CMS). In water-containing solutions, CMS undergoes a spontaneous hydrolysis to form a complex mixture of partially sulfomethylated derivatives and CS. Pharmacokinetic of CS is dependent on the route of administration, i.e. parenteral, intramuscular, nebulized, intrathecal/intraventricular. Renal toxicity is the most common adverse effect of CS treatment, as the drug is excreted primarily by the kidney and elevated levels of CS may further impair renal function, with a dose-dependent effect. Clinical manifestations of CS associated nephrotoxicity include acute kidney injury, proteinuria and tubular damage. Only few data are currently available on the effects of different renal replacement therapy modalities on CS pharmacokinetics. In patients undergoing the most efficient forms of renal replacement therapies, the extracorporeal clearance of CMS may result in a substantial removal of the antibiotic. Thus, in this setting, the recommended daily doses should be increased. Future studies should better explore CS pharmacokinetics in patients undergoing different modalities of renal replacement therapy.

摘要

黏菌素(CS)是一种具有杀菌活性的多粘菌素,越来越多地用于治疗与多重耐药革兰氏阴性菌(MDR - GNB)相关的医院感染。静脉注射的CS通常以毒性较小的前体药物形式给药,即黏菌素甲磺酸钠(CMS)。在含水溶液中,CMS会自发水解,形成部分磺甲基化衍生物和CS的复杂混合物。CS的药代动力学取决于给药途径,即肠胃外、肌肉注射、雾化、鞘内/脑室内给药。肾毒性是CS治疗最常见的不良反应,因为该药物主要通过肾脏排泄,CS水平升高可能会进一步损害肾功能,具有剂量依赖性效应。CS相关肾毒性的临床表现包括急性肾损伤、蛋白尿和肾小管损伤。目前关于不同肾脏替代治疗方式对CS药代动力学影响的数据很少。在接受最有效的肾脏替代治疗形式的患者中,CMS的体外清除可能会导致抗生素大量清除。因此,在这种情况下,建议增加每日剂量。未来的研究应该更好地探索接受不同肾脏替代治疗方式的患者的CS药代动力学。

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