Rescuing the Last-Line Polymyxins: Achievements and Challenges.
Rescuing the Last-Line Polymyxins: Achievements and Challenges.
复制标题
DOI：
10.1124/pharmrev.120.000020
复制
发表时间：
2021-04
影响因子：
21.1
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Nang SC;Azad MAK;Velkov T;Zhou QT;Li J
抗生素耐药性是一个重大的全球健康挑战，令人担忧的是，几种关键的革兰氏阴性病原体可能对目前可用的大多数抗生素产生耐药性。多粘菌素已作为治疗多重耐药革兰氏阴性菌（特别是鲍曼不动杆菌、铜绿假单胞菌和肠球菌）引起的感染的最后一线治疗选择而恢复。多粘菌素在20世纪40年代末首次被发现，但在20世纪50年代末批准后不久由于毒性而被放弃（例如，肾毒性）和当时批准的“更安全”抗生素的可用性。因此，直到最近，世界各地的几个研究小组做出了巨大的努力来阐明多粘菌素的化学，微生物学，药代动力学/药效学和毒理学特性，对多粘菌素的知识一直是稀缺的。主要成就之一是开发了第一个基于科学的粘菌素剂量方案，这对于确保其在患者中的安全和有效使用至关重要。虽然尚未制定多粘菌素B的指南，但目前正在进行一项大型临床试验，以优化其临床使用。重要的是，开发了几种新的、更安全的多粘菌素样脂肽，以克服目前使用的多粘菌素B和粘菌素的肾毒性、对肺部感染的不良疗效和狭窄的治疗窗。本文综述了多粘菌素类药物的最新研究成果，并重点介绍了在优化其临床应用和发现新一代多粘菌素方面面临的主要挑战。为了从革兰氏阴性“超级细菌”引起的致命感染中挽救生命，必须尽一切努力提高最后一线多粘菌素的临床效用。抗生素耐药性对全球健康构成重大威胁。多药耐药（MDR）细菌感染的日益流行已被全球领先的卫生组织和当局所强调。多粘菌素是抵抗难治性MDR革兰氏阴性病原体的最后防线。不幸的是，直到最近，关于多粘菌素的药理学信息非常有限。本综述全面概述了多粘菌素药理学和临床应用的主要成就和挑战，以及如何利用最新发现来改善全球临床实践。
Antibiotic resistance is a major global health challenge and, worryingly, several key Gram negative pathogens can become resistant to most currently available antibiotics. Polymyxins have been revived as a last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram negative bacteria, in particular Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales. Polymyxins were first discovered in the late 1940s but were abandoned soon after their approval in the late 1950s as a result of toxicities (e.g., nephrotoxicity) and the availability of “safer” antibiotics approved at that time. Therefore, knowledge on polymyxins had been scarce until recently, when enormous efforts have been made by several research teams around the world to elucidate the chemical, microbiological, pharmacokinetic/pharmacodynamic, and toxicological properties of polymyxins. One of the major achievements is the development of the first scientifically based dosage regimens for colistin that are crucial to ensure its safe and effective use in patients. Although the guideline has not been developed for polymyxin B, a large clinical trial is currently being conducted to optimize its clinical use. Importantly, several novel, safer polymyxin-like lipopeptides are developed to overcome the nephrotoxicity, poor efficacy against pulmonary infections, and narrow therapeutic windows of the currently used polymyxin B and colistin. This review discusses the latest achievements on polymyxins and highlights the major challenges ahead in optimizing their clinical use and discovering new-generation polymyxins. To save lives from the deadly infections caused by Gram negative “superbugs,” every effort must be made to improve the clinical utility of the last-line polymyxins. Antimicrobial resistance poses a significant threat to global health. The increasing prevalence of multidrug-resistant (MDR) bacterial infections has been highlighted by leading global health organizations and authorities. Polymyxins are a last-line defense against difficult-to-treat MDR Gram negative pathogens. Unfortunately, the pharmacological information on polymyxins was very limited until recently. This review provides a comprehensive overview on the major achievements and challenges in polymyxin pharmacology and clinical use and how the recent findings have been employed to improve clinical practice worldwide.
登录
查看更多内容
影响因子：
4.9
作者：
Ahmed, Maizbha U.;Velkov, Tony;Li, Jian
通讯作者：
Li, Jian
影响因子：
4.8
作者：
Abe, T;Kakyo, M;Yawo, H
通讯作者：
Yawo, H
影响因子：
1.8
作者：
Al-Sweih, N. A.;Al-Hubail, M. A.;Rotimi, V. O.
通讯作者：
Rotimi, V. O.
影响因子：
9.4
作者：
Arroyo, LA;García-Curiel, A;Aznar, J
通讯作者：
Aznar, J
影响因子：
5.2
作者：
AbuOun, Manal;Stubberfield, Emma J.;Anjum, Muna F.
通讯作者：
Anjum, Muna F.