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控制人类抗真菌耐药性风险的潜在策略:全面综述

Potential Strategies to Control the Risk of Antifungal Resistance in Humans: A Comprehensive Review.

作者信息

Rabaan Ali A, Sulaiman Tarek, Al-Ahmed Shamsah H, Buhaliqah Zainab A, Buhaliqah Ali A, AlYuosof Buthina, Alfaresi Mubarak, Al Fares Mona A, Alwarthan Sara, Alkathlan Mohammed S, Almaghrabi Reem S, Abuzaid Abdulmonem A, Altowaileb Jaffar A, Al Ibrahim Maha, AlSalman Eman M, Alsalman Fatimah, Alghounaim Mohammad, Bueid Ahmed S, Al-Omari Awad, Mohapatra Ranjan K

机构信息

Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia.

College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.

出版信息

Antibiotics (Basel). 2023 Mar 18;12(3):608. doi: 10.3390/antibiotics12030608.

Abstract

Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used in clinical settings. Antifungal therapy is the mainstay of patient management for acute and chronic mycoses. However, the limited availability of antifungal drug classes limits the range of available treatments. Additionally, several drawbacks to treating mycoses include unfavourable side effects, a limited activity spectrum, a paucity of targets, and fungal resistance, all of which continue to be significant issues in developing antifungal drugs. The emergence of antifungal drug resistance has eliminated accessible drug classes as treatment choices, which significantly compromises the clinical management of fungal illnesses. In some situations, the emergence of strains resistant to many antifungal medications is a major concern. Although new medications have been developed to address this issue, antifungal drug resistance has grown more pronounced, particularly in patients who need long-term care or are undergoing antifungal prophylaxis. Moreover, the mechanisms that cause resistance must be well understood, including modifications in drug target affinities and abundances, along with biofilms and efflux pumps that diminish intracellular drug levels, to find novel antifungal drugs and drug targets. In this review, different classes of antifungal agents, and their resistance mechanisms, have been discussed. The latter part of the review focuses on the strategies by which we can overcome this serious issue of antifungal resistance in humans.

摘要

真菌感染正成为免疫系统较弱人群发病和死亡的主要原因之一。尽管人们对真菌感染的认识有所提高,治疗方法也有所改进,但由于临床使用的抗真菌药物耐药性不断出现,真菌病正变得越来越普遍。抗真菌治疗是急性和慢性真菌病患者管理的主要手段。然而,抗真菌药物种类有限,限制了可用治疗方法的范围。此外,治疗真菌病的几个缺点包括不良副作用、活性谱有限、靶点稀少以及真菌耐药性,所有这些在开发抗真菌药物方面仍然是重大问题。抗真菌药物耐药性的出现使一些可用药物种类不再适用于治疗选择,这严重影响了真菌疾病的临床管理。在某些情况下,对多种抗真菌药物耐药的菌株的出现是一个主要问题。尽管已经开发出新的药物来解决这个问题,但抗真菌药物耐药性变得更加明显,特别是在需要长期护理或正在接受抗真菌预防的患者中。此外,必须充分了解导致耐药性的机制,包括药物靶点亲和力和丰度的改变,以及生物膜和外排泵降低细胞内药物水平的机制,以便找到新的抗真菌药物和药物靶点。在这篇综述中,讨论了不同类别的抗真菌药物及其耐药机制。综述的后半部分重点讨论了我们可以克服人类抗真菌耐药性这一严重问题的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b908/10045400/9a7358152df6/antibiotics-12-00608-g009.jpg

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