Faculté de Médecine et de Pharmacie, IRD, APHM, MEPHI, Aix Marseille Univ, Marseille, France.
IHU Méditerranée Infection, Marseille, France.
Front Cell Infect Microbiol. 2019 Jun 11;9:193. doi: 10.3389/fcimb.2019.00193. eCollection 2019.
The emergence of new resistance mechanisms, the failure of classical antibiotics in clinic, the decrease in the development of antibiotics in the industry are all challenges that lead us to consider new strategies for the treatment of infectious diseases. Indeed, in recent years controversy has intensified over strains resistant to carbapenem and/or colistin. Various therapeutic solutions are used to overcome administration of last line antibiotics. In this context, drug repurposing, which consists of using a non-antibiotic compound to treat multi-drug resistant bacteria (MDR), is encouraged. In this review, we first report what may have led to drug repurposing. Main definitions, advantages and drawbacks are summarized. Three major methods are described: phenotypic, computational and serendipity. In a second time we will focus on the current knowledge in drug repurposing for carbapenem and colistin-resistant bacteria with different studies describing repurposed compounds tested on Gram-negative bacteria. Furthermore, we show that drug combination therapies can increase successful by drug repurposing strategy. In conclusion, we discuss the pharmaceutical industries that have little interest in reprofiling drugs due to lack of profits. We also consider what a clinician might think of the indications of these uncommon biologists to treat MDR bacterial infections and avoid therapeutic impasses.
新耐药机制的出现、经典抗生素在临床上的失败、抗生素在工业上的发展减少，这些都给我们带来了挑战，需要考虑新的传染病治疗策略。事实上，近年来，对碳青霉烯类和/或黏菌素耐药的菌株引起了更多的争议。为了克服最后一线抗生素的使用，人们使用了各种治疗方法。在这种情况下，药物再利用（使用非抗生素化合物治疗多药耐药菌）受到了鼓励。在这篇综述中，我们首先报告了可能导致药物再利用的原因。总结了主要的定义、优点和缺点。描述了三种主要的方法：表型、计算和偶然发现。在第二部分，我们将重点介绍目前关于碳青霉烯类和黏菌素耐药菌药物再利用的知识，不同的研究描述了用于革兰氏阴性菌的再利用化合物。此外，我们还表明，药物联合治疗可以通过药物再利用策略增加成功率。总之，我们讨论了制药行业对药物重新定位缺乏兴趣，因为这没有利润。我们还考虑了临床医生对这些不常见的生物学家治疗多药耐药菌感染的指示的看法，以避免治疗僵局。
