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老药新用:新型半合成氨基糖苷类药物普拉佐米星

Teaching an Old Class New Tricks: A Novel Semi-Synthetic Aminoglycoside, Plazomicin.

作者信息

Abdul-Mutakabbir Jacinda C, Kebriaei Razieh, Jorgensen Sarah C J, Rybak Michael J

机构信息

Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.

Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, MI, USA.

出版信息

Infect Dis Ther. 2019 Jun;8(2):155-170. doi: 10.1007/s40121-019-0239-0. Epub 2019 Mar 9.

Abstract

The emergence of multi-drug resistant (MDR) Gram-negative pathogens has become a serious worldwide health concern. Gram-negative bacteria such as Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli, Enterobacter spp.,) Acinetobacter spp., and Pseudomonas aeruginosa have rendered most antibiotics inactive, leaving aminoglycosides and polymyxins. Plazomicin (formerly ACHN-490), is a neoglycoside with unique structural modifications to the aminoglycoside pharmacophore that impart activity against many MDR Gram-negative organisms. ACHN-490 was recently approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections caused by MDR Enterobacteriaceae. In this era of increasing Gram-negative resistance, it is imperative to critically evaluate new antibiotics so that we understand how to use them optimally. The objective of this article is to discuss available data detailing plazomicin's biochemistry, pharmacokinetic/pharmacodynamic characteristics, in-vitro activity and current progress in clinical trials. In addition, plazomicin's potential role in therapy for the treatment of MDR Gram-negative infections will be discussed.

摘要

多重耐药(MDR)革兰氏阴性病原体的出现已成为全球严重的健康问题。革兰氏阴性菌,如肠杆菌科细菌(肺炎克雷伯菌、大肠杆菌、肠杆菌属等)、不动杆菌属和铜绿假单胞菌,已使大多数抗生素失效,仅留下氨基糖苷类和多粘菌素类。普拉佐米星(原ACHN-490)是一种新型糖苷类药物,对氨基糖苷类药效基团进行了独特的结构修饰,使其对许多多重耐药革兰氏阴性菌具有活性。ACHN-490最近被美国食品药品监督管理局批准用于治疗由多重耐药肠杆菌科细菌引起的复杂性尿路感染。在革兰氏阴性菌耐药性不断增加的时代,严格评估新型抗生素至关重要,以便我们了解如何最佳地使用它们。本文的目的是讨论有关普拉佐米星的生物化学、药代动力学/药效学特征、体外活性以及当前临床试验进展的现有数据。此外,还将讨论普拉佐米星在治疗多重耐药革兰氏阴性菌感染中的潜在作用。

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