Laboratory of Microbiology, Department of Biochemistry & Microbiology, Ghent University, Gent, Belgium.
J Antimicrob Chemother. 2013 Feb;68(2):275-83. doi: 10.1093/jac/dks405. Epub 2012 Oct 16.
Antimicrobial resistance is a serious problem because of the scarcity of new antibiotics effective against pathogens such as methicillin-resistant Staphylococcus aureus, β-lactamase-producing Gram-negative bacteria and multidrug-resistant Mycobacterium tuberculosis. Extensively drug resistance is particularly worrying in tuberculosis (TB), since the causative bacteria have become resistant to almost all available first- and second-line drugs and resistance is a threat to achieving control of the disease. Development of new drugs is a lengthy and costly endeavour. This is a particular problem for antibiotics, usage of which is likely to be of limited duration, and is even more true of antibiotics whose use is restricted to the treatment of a disease, such as TB, that is considered to be 'poverty related', and for which the return on the investment is seen as non-attractive. In spite of this, there is an emerging pipeline of new drugs under development that hopefully will bring new anti-TB drugs to the market in the near future. The strategy of drug repurposing, finding new uses for existing approved medicines, has seen unexpected success in other medical areas. More than one blockbuster drug has originated from this strategy. And in the field of TB, there have been several examples in recent years of this approach leading to the use of drugs for which there is undeniable evidence of efficacy in the treatment of the disease, the best example being the fluoroquinolones, which were not developed originally to treat TB. This article reviews some examples of repurposing of drugs in the treatment of TB, newer candidates for repurposing for which there is already preliminary evidence of activity and possible new options that merit further investigation.
由于缺乏对耐甲氧西林金黄色葡萄球菌、产β-内酰胺酶革兰氏阴性菌和耐多药结核分枝杆菌等病原体有效的新抗生素，抗菌药物耐药性是一个严重的问题。广泛耐药性在结核病 (TB) 中尤其令人担忧，因为导致结核病的细菌几乎对所有现有一线和二线药物都产生了耐药性，而且耐药性是实现该疾病控制的威胁。开发新药是一项漫长而昂贵的努力。这对于抗生素来说是一个特别的问题，因为抗生素的使用可能是有限的，对于那些只能用于治疗被认为是“与贫困相关”的疾病（如结核病）的抗生素来说更是如此，因为投资回报被认为没有吸引力。尽管如此，目前正在开发新的药物，有望在不久的将来为结核病带来新的抗结核药物。药物再利用的策略，即为现有批准的药物寻找新的用途，在其他医学领域取得了出人意料的成功。不止一种重磅炸弹药物源自这一策略。在结核病领域，近年来有几个例子表明，这种方法导致了一些药物的使用，这些药物在治疗结核病方面具有不可否认的疗效，最好的例子是氟喹诺酮类药物，它们最初并不是为治疗结核病而开发的。本文回顾了一些药物在结核病治疗中的再利用实例，以及已经有初步活性证据的新候选药物，以及可能值得进一步研究的新选择。
