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对抗多重耐药鲍曼不动杆菌的新型抗菌剂及新兴疗法

Novel antibacterial agents and emerging therapies in the fight against multidrug-resistant Acinetobacter baumannii.

作者信息

Oladipo Elijah Kolawole, Adeyemo Stephen Feranmi, Oluwasanya Glory Jesudara, Adaramola Esther Oluwadarasimi, Akintola Shalom Busayo, Afolabi Victor Oluwatobi, Ajagbe Joel Damilare, Ojo Oluwadara Hannah, Kolapo Emmanuel Pelumi, Owoeye Emmanuel, Jimah Esther Moradeyo, Ayeleso Ademola O, Onyeaka Helen

机构信息

Division of Pharmacotherapies Design and Development, Helix Biogen Institute, Ogbomoso, Oyo State, Nigeria; Division of Vaccine Design and Development, Helix Biogen Institute, Ogbomoso, Oyo State, Nigeria; Department of Microbiology, Laboratory of Molecular Biology, Immunology and Bioinformatics, Adeleke University, Ede, Osun State, Nigeria; Department of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B12 2TT, UK.

Division of Vaccine Design and Development, Helix Biogen Institute, Ogbomoso, Oyo State, Nigeria.

出版信息

Microb Pathog. 2025 Mar;200:107361. doi: 10.1016/j.micpath.2025.107361. Epub 2025 Jan 31.

Abstract

Acinetobacter baumannii, a multidrug-resistant pathogen, poses a critical challenge in healthcare settings due to its adaptability and limited treatment options. The global rise in antimicrobial resistance (AMR) has underscored the urgent need for novel therapeutic strategies to combat infections caused by extensively drug-resistant (EDR) and pan-drug-resistant (PDR) A. baumannii. Traditional antibiotic discovery methods, such as whole-cell screening, have fallen short, consistently identifying drugs prone to resistance. This review explores the discovery of new anti-bacterial agents targeting A. baumannii, focusing on emerging therapeutic approaches, including nanoparticle-based therapies, antimicrobial peptides, and antibiotic combination therapies. Nanoparticle-based approaches, leveraging enhanced penetration and multi-mechanistic action, show promise in overcoming resistance, though challenges such as toxicity and biocompatibility persist. Additionally, combination therapies, such as polymyxins with carbapenems, have demonstrated efficacy in clinical settings. This review also highlights the limitations of current therapies, the mechanisms of bacterial resistance, and the role of alternative strategies like bacteriophage therapy. Emphasis is placed on the need for further research into overcoming cross-resistance and enhancing therapeutic efficacy against A. baumannii. The review concludes by discussing the importance of advancing research into novel agents, optimizing dosage strategies, and addressing the challenges posed by toxicity to ensure the effective treatment of A. baumannii infections in both hospital and community settings.

摘要

鲍曼不动杆菌是一种多重耐药病原体,因其适应性强且治疗选择有限,在医疗环境中构成了严峻挑战。全球抗菌药物耐药性(AMR)的上升凸显了迫切需要新的治疗策略来对抗由广泛耐药(EDR)和泛耐药(PDR)鲍曼不动杆菌引起的感染。传统的抗生素发现方法,如全细胞筛选,已显不足,不断发现容易产生耐药性的药物。本综述探讨了针对鲍曼不动杆菌的新型抗菌剂的发现,重点关注新兴的治疗方法,包括基于纳米颗粒的疗法、抗菌肽和抗生素联合疗法。基于纳米颗粒的方法利用增强的穿透力和多机制作用,在克服耐药性方面显示出前景,尽管毒性和生物相容性等挑战仍然存在。此外,联合疗法,如多粘菌素与碳青霉烯类药物的联合,已在临床环境中证明有效。本综述还强调了当前疗法的局限性、细菌耐药机制以及噬菌体疗法等替代策略的作用。重点在于需要进一步研究克服交叉耐药性并提高针对鲍曼不动杆菌的治疗效果。综述最后讨论了推进新型药物研究、优化剂量策略以及应对毒性带来的挑战的重要性,以确保在医院和社区环境中有效治疗鲍曼不动杆菌感染。

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