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全球临床前抗菌药物研发管道的多年分析:趋势与差距。

Multi-year analysis of the global preclinical antibacterial pipeline: trends and gaps.

机构信息

AMR Division, World Health Organization, Geneva, Switzerland.

Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, Boston, Massachusetts, USA.

出版信息

Antimicrob Agents Chemother. 2024 Aug 7;68(8):e0053524. doi: 10.1128/aac.00535-24. Epub 2024 Jul 15.

Abstract

Antimicrobial resistance (AMR) is a major global health threat estimated to have caused the deaths of 1.27 million people in 2019, which is more than HIV/AIDS and malaria deaths combined. AMR also has significant consequences on the global economy. If not properly addressed, AMR could immensely impact the world's economy, further increasing the poverty burden in low- and middle-income countries. To mitigate the risk of a post-antibiotic society, where the ability to effectively treat common bacterial infections is being severely threatened, it is necessary to establish a continuous supply of new and novel antibacterial medicines. However, there are gaps in the current pipeline that will prove difficult to address, given the time required to develop new agents. To understand the status of upstream antibiotic development and the challenges faced by drug developers in the early development stage, the World Health Organization has regularly assessed the preclinical and clinical antibacterial development pipeline. The review identifies potential new classes of antibiotics or novel mechanisms of action that can better address resistant bacterial strains. This proactive approach is necessary to stay ahead of evolving resistance patterns and to support the availability of effective treatment options. This review examines the trends in preclinical development and attempts to identify gaps and potential opportunities to overcome the numerous hurdles in the early stages of the antibacterial research and development space.

摘要

抗菌药物耐药性(AMR)是一项重大的全球健康威胁,据估计,其在 2019 年导致了 127 万人死亡,这一数字超过了艾滋病毒/艾滋病和疟疾死亡人数的总和。AMR 还对全球经济产生了重大影响。如果得不到妥善处理,AMR 可能会对世界经济产生巨大影响,进一步加重中低收入国家的贫困负担。为了减轻后抗生素时代的风险,在这个时代,有效治疗常见细菌感染的能力受到严重威胁,有必要建立新的和新颖的抗菌药物的持续供应。然而,鉴于开发新制剂所需的时间,目前的管道存在差距,这将很难解决。为了了解上游抗生素开发的现状和药物开发者在早期开发阶段面临的挑战,世界卫生组织定期评估临床前和临床抗菌药物开发管道。该审查确定了具有潜在新类别的抗生素或新作用机制的药物,这些药物可以更好地应对耐药菌。这种积极主动的方法对于跟上不断变化的耐药模式以及支持有效的治疗选择的可获得性是必要的。本综述考察了临床前开发的趋势,并试图确定差距和潜在的机会,以克服抗菌药物研发领域早期阶段的众多障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ed/11304740/aac542f72ec6/aac.00535-24.f001.jpg

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