抗药性
附带损害
药品
抵押品
药物开发
限制
医学
药理学
生物
微生物学
业务
财务
犯罪学
机械工程
工程类
社会学
作者
Lejla Imamovic,Morten Otto Alexander Sommer
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2013-09-25
卷期号:5 (204)
被引量:354
标识
DOI:10.1126/scitranslmed.3006609
摘要
New drug deployment strategies are imperative to address the problem of drug resistance, which is limiting the management of infectious diseases and cancers. We evolved resistance in Escherichia coli toward 23 drugs used clinically for treating bacterial infections and mapped the resulting collateral sensitivity and resistance profiles, revealing a complex collateral sensitivity network. On the basis of these data, we propose a new treatment framework--collateral sensitivity cycling--in which drugs with compatible collateral sensitivity profiles are used sequentially to treat infection and select against drug resistance development. We identified hundreds of such drug sets and demonstrated that the antibiotics gentamicin and cefuroxime can be deployed cyclically such that the treatment regimen selected against resistance to either drug. We then validated our findings with related bacterial pathogens. These results provide proof of principle for collateral sensitivity cycling as a sustainable treatment paradigm that may be generally applicable to infectious diseases and cancer.
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