Overcoming antibiotic resistance: the potential and pitfalls of drug repurposing.

IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Journal of Drug Targeting Pub Date : 2024-11-12 DOI:10.1080/1061186X.2024.2424895
Mohammad Abavisani, Alireza Khoshrou, Souzan Eshaghian, Sercan Karav, Amirhossein Sahebkar
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Abstract

Since its emergence shortly after the discovery of penicillin, antibiotic resistance has escalated dramatically, posing a significant health threat and economic burden. Drug repositioning, or drug repurposing, involves identifying new therapeutic applications for existing drugs, utilising their established safety profiles and pharmacological data to swiftly provide effective treatments against resistant pathogens. Several drugs, including otilonium bromide, penfluridol, eltrombopag, ibuprofen, and ceritinib, have demonstrated potent antibacterial activity against multidrug-resistant (MDR) bacteria. These drugs can disrupt biofilms, damage bacterial membranes, and inhibit bacterial growth. The combination of repurposed drugs with conventional antibiotics can reduce the required dosage of individual drugs, mitigate side effects, and delay the development of resistance, making it a promising strategy against MDR bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Despite its promise, drug repurposing faces challenges such as potential off-target effects, toxicity, and regulatory and intellectual property issues, necessitating rigorous evaluations and strategic solutions. This article aims to explore the potential of drug repurposing as a strategy to combat antibiotic resistance, examining its benefits, challenges, and future prospects. We address the legal, economic, and practical challenges associated with repurposing existing drugs, highlight successful examples, and propose solutions to enhance the efficacy and viability of this approach in combating MDR bacterial infections.

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克服抗生素耐药性:药物再利用的潜力与陷阱。
自从青霉素发现后不久出现抗生素耐药性以来,抗生素耐药性急剧升级,对健康构成了严重威胁,也给经济造成了沉重负担。抗击抗生素耐药性,尤其是革兰氏阴性菌(GNB)和耐药结核分枝杆菌的耐药性,需要创新研究、大量资金投入和全球合作,以保障公众健康并制定可持续的解决方案。药物再定位或药物再利用涉及为现有药物确定新的治疗用途,利用其既有的安全性特征和药理学数据,迅速提供针对耐药病原体的有效治疗。包括奥替溴铵、戊氟利多、艾曲波帕、布洛芬和塞瑞替尼在内的几种药物对耐多药(MDR)细菌具有很强的抗菌活性。这些药物可以破坏生物膜,破坏细菌膜,抑制细菌生长。此外,将再利用药物与传统抗生素结合使用,可以减少单种药物的用量,减轻副作用,延缓耐药性的产生,因此是一种很有前景的抗金黄色葡萄球菌、肺炎克雷伯氏菌、铜绿假单胞菌和大肠埃希氏菌等 MDR 细菌的策略。尽管药物再利用前景广阔,但它也面临着潜在的脱靶效应、毒性、监管和知识产权问题等挑战,因此必须进行严格评估并制定战略解决方案。本文旨在探讨药物再利用作为对抗抗生素耐药性策略的潜力,研究其益处、挑战和未来前景。我们探讨了与现有药物再利用相关的法律、经济和实际挑战,重点介绍了成功案例,并提出了解决方案,以提高这种方法在抗击 MDR 细菌感染方面的有效性和可行性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
9.10
自引率
0.00%
发文量
165
审稿时长
2 months
期刊介绍: Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
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