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抗生素耐药危机,聚焦于美国。

The antibiotic resistance crisis, with a focus on the United States.

作者信息

Martens Evan, Demain Arnold L

机构信息

Cempra, Inc., Chapel Hill, NC, USA.

Research Institute of Scientists Emeriti (R.I.S.E.), Drew University, Madison, NJ, USA.

出版信息

J Antibiot (Tokyo). 2017 May;70(5):520-526. doi: 10.1038/ja.2017.30. Epub 2017 Mar 1.

Abstract

Beginning with the discovery of penicillin by Alexander Fleming in the late 1920s, antibiotics have revolutionized the field of medicine. They have saved millions of lives each year, alleviated pain and suffering, and have even been used prophylactically for the prevention of infectious diseases. However, we have now reached a crisis where many antibiotics are no longer effective against even the simplest infections. Such infections often result in an increased number of hospitalizations, more treatment failures and the persistence of drug-resistant pathogens. Of particular concern are organisms such as methicillin-resistant Staphylococcus aureus, Clostridium difficile, multidrug and extensively drug-resistant Mycobacterium tuberculosis, Neisseria gonorrhoeae, carbapenem-resistant Enterobacteriaceae and bacteria that produce extended spectrum β-lactamases, such as Escherichia coli. To make matters worse, there has been a steady decline in the discovery of new and effective antibiotics for a number of reasons. These include increased costs, lack of adequate support from the government, poor returns on investment, regulatory hurdles and pharmaceutical companies that have simply abandoned the antibacterial arena. Instead, many have chosen to focus on developing drugs that will be used on a chronic basis, which will offer a greater profit and more return on investment. Therefore, there is now an urgent need to develop new and useful antibiotics to avoid returning to the 'pre-antibiotic era'. Some potential opportunities for antibiotic discovery include better economic incentives, genome mining, rational metabolic engineering, combinatorial biosynthesis and further exploration of the earth's biodiversity.

摘要

自20世纪20年代末亚历山大·弗莱明发现青霉素以来,抗生素彻底改变了医学领域。它们每年挽救了数百万人的生命,减轻了痛苦,甚至还被用于预防传染病。然而,我们现在面临一场危机,许多抗生素甚至对最简单的感染都不再有效。这类感染常常导致住院人数增加、治疗失败增多以及耐药病原体持续存在。特别令人担忧的是耐甲氧西林金黄色葡萄球菌、艰难梭菌、多重耐药和广泛耐药结核分枝杆菌、淋病奈瑟菌、耐碳青霉烯肠杆菌科细菌以及产超广谱β-内酰胺酶的细菌,如大肠杆菌等微生物。更糟糕的是,由于多种原因,新的有效抗生素的发现一直在稳步下降。这些原因包括成本增加、政府缺乏足够支持、投资回报不佳、监管障碍以及制药公司干脆放弃抗菌领域。相反,许多公司选择专注于开发将长期使用的药物,这将带来更大利润和更高投资回报。因此,现在迫切需要开发新的有用抗生素,以避免回到“抗生素前时代”。抗生素发现的一些潜在机会包括更好的经济激励、基因组挖掘、合理的代谢工程、组合生物合成以及对地球生物多样性的进一步探索。

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