College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, China.
Theranostics. 2021 Mar 4;11(10):4910-4928. doi: 10.7150/thno.56205. eCollection 2021.
Antimicrobial resistance has been a global health challenge that threatens our ability to control and treat life-threatening bacterial infections. Despite ongoing efforts to identify new drugs or alternatives to antibiotics, no new classes of antibiotic or their alternatives have been clinically approved in the last three decades. A combination of antibiotics and non-antibiotic compounds that could inhibit bacterial resistance determinants or enhance antibiotic activity offers a sustainable and effective strategy to confront multidrug-resistant bacteria. In this review, we provide a brief overview of the co-evolution of antibiotic discovery and the development of bacterial resistance. We summarize drug-drug interactions and uncover the art of repurposing non-antibiotic drugs as potential antibiotic adjuvants, including discussing classification and mechanisms of action, as well as reporting novel screening platforms. A pathogen-by-pathogen approach is then proposed to highlight the critical value of drug repurposing and its therapeutic potential. Finally, general advantages, challenges and development trends of drug combination strategy are discussed.
抗菌药物耐药性一直是一个全球性的健康挑战，威胁着我们控制和治疗危及生命的细菌感染的能力。尽管我们一直在努力寻找新的药物或抗生素替代品，但在过去的三十年中，没有新的抗生素类别或其替代品在临床上得到批准。将抗生素和非抗生素化合物结合使用，可以抑制细菌耐药决定因素或增强抗生素的活性，为应对多药耐药菌提供了一种可持续和有效的策略。在这篇综述中，我们简要概述了抗生素发现和细菌耐药性发展的共同进化。我们总结了药物-药物相互作用，并揭示了将非抗生素药物重新用作潜在抗生素佐剂的艺术，包括讨论分类和作用机制，并报告新的筛选平台。然后提出了一种针对病原体的方法，以突出药物再利用的关键价值及其治疗潜力。最后，讨论了药物联合策略的一般优势、挑战和发展趋势。
