Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?
Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?
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DOI：
10.1038/nrd4675
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发表时间：
2015-12-01
影响因子：
120.1
通讯作者：
Brown, David
中科院分区：
文献类型：
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作者：
Brown, David
人们对抗生素耐药性的担忧日益增加，需要新的抗生素，特别是针对革兰氏阴性菌的抗生素。然而，即使能够克服科学障碍，也可能需要数十年才能获得足够数量的此类抗生素。作为一种临时解决方案，抗生素耐药性可以通过联合使用适当的非抗生素药物和失败的抗生素来“打破”。目前没有抗菌适应症的几种市售药物可以直接杀死细菌，当与现有抗生素联合使用时降低抗生素最低抑菌浓度和/或通过对宿主先天免疫的影响调节宿主防御，特别是通过改变炎症和自噬。本文讨论了这种“抗生素耐药性破坏剂”如何有助于减少抗生素耐药性问题，并分析了进一步调查的候选人的优先名单。
Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation.