Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Int J Antimicrob Agents. 2011 Jan;37(1):2-9. doi: 10.1016/j.ijantimicag.2010.08.018. Epub 2010 Nov 13.
Although there has been a relentless increase in resistance to antimicrobial agents amongst important bacterial pathogens throughout the world, it is well known that the number of new antimicrobial agents being brought to the market has undergone a steady decline in the past several decades. There are a number of reasons for this, which are detailed in this article, but there is also a great deal of continuing research to find new effective antimicrobials, much of it now being carried out in academic centres and especially in small biotechnology companies, rather than by large pharma. Whilst classic screening methods and chemical modification of known antimicrobial agents continue to produce potential leads for new antimicrobial agents, a number of other approaches are being investigated. These include the search for potentiators of the activity of known antimicrobial agents and the development of hybrid agents, novel membrane-active drugs, and inhibitors of bacterial virulence and pathogenesis. A number of new bacterial targets are also being exploited, as are bacteriophages and their lytic enzymes. Given the amount of investigation presently underway, it is clear that although the antibiotic pipeline is not as promising as it was half a century ago, it is far from dry.
虽然世界各地的重要细菌病原体对抗菌药物的耐药性一直在无情地增加，但众所周知，过去几十年里推向市场的新抗菌药物数量一直在稳步下降。造成这种情况的原因有很多，本文对此进行了详细说明，但仍有大量持续的研究致力于寻找新的有效抗菌药物，其中很大一部分现在是在学术中心进行的，特别是在小型生物技术公司中，而不是大型制药公司。虽然经典的筛选方法和对已知抗菌药物的化学修饰继续为新抗菌药物提供潜在的先导化合物，但也在研究其他一些方法。其中包括寻找已知抗菌药物活性增强剂和开发混合药物、新型膜活性药物以及抑制细菌毒力和发病机制的抑制剂。也正在开发一些新的细菌靶点，以及噬菌体及其裂解酶。鉴于目前正在进行的大量研究，很明显，尽管抗生素管道不像半个世纪前那样有希望，但它远未枯竭。
