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治疗耐药性耳念珠菌的新兴和未来策略。

Emerging and future strategies in the management of recalcitrant Candida auris.

机构信息

Bristol Dental School, University of Bristol BS1 2LY, Bristol, United Kingdom.

Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China.

出版信息

Med Mycol. 2022 Mar 17;60(4). doi: 10.1093/mmy/myac008.

Abstract

UNLABELLED

Candida auris is an emerging, multi drug resistant fungal pathogen that has caused infectious outbreaks in over 45 countries since its first isolation over a decade ago, leading to in-hospital crude mortality rates as high as 72%. The fungus is also acclimated to disinfection procedures and persists for weeks in nosocomial ecosystems. Alarmingly, the outbreaks of C. auris infections in Coronavirus Disease-2019 (COVID-19) patients have also been reported. The pathogenicity, drug resistance and global spread of C. auris have led to an urgent exploration of novel, candidate antifungal agents for C. auris therapeutics. This narrative review codifies the emerging data on the following new/emerging antifungal compounds and strategies: antimicrobial peptides, combinational therapy, immunotherapy, metals and nano particles, natural compounds, and repurposed drugs. Encouragingly, a vast majority of these exhibit excellent anti- C. auris properties, with promising drugs now in the pipeline in various stages of development. Nevertheless, further research on the modes of action, toxicity, and the dosage of the new formulations are warranted. Studies are needed with representation from all five C. auris clades, so as to produce data of grater relevance, and broader significance and validity.

LAY SUMMARY

Elimination of Candida auris that causes deadly infections to susceptible individuals is extremely challenging due to the lack of effective treatment options. Promising, new antifungal agents and strategies are being developed and further refinement will facilitate their clinical use in the near future.

摘要

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假丝酵母菌耳念珠菌是一种新兴的、多药耐药的真菌病原体,自十多年前首次分离以来,已在 45 个以上国家引起了传染性爆发,导致院内粗死亡率高达 72%。该真菌还能适应消毒程序,并在医院环境中持续存在数周。令人震惊的是,假丝酵母菌耳念珠菌感染在 2019 年冠状病毒病(COVID-19)患者中的爆发也有报道。假丝酵母菌耳念珠菌的致病性、耐药性和全球传播导致人们迫切需要探索新型候选抗真菌药物来治疗假丝酵母菌耳念珠菌。本综述综述了以下新出现/新兴抗真菌化合物和策略的最新数据:抗菌肽、联合治疗、免疫疗法、金属和纳米颗粒、天然化合物和重新利用的药物。令人鼓舞的是,绝大多数这些化合物对假丝酵母菌耳念珠菌表现出极好的抗菌特性,有前途的药物现在正在不同开发阶段的管道中。然而,需要对新制剂的作用模式、毒性和剂量进行进一步研究。需要来自假丝酵母菌耳念珠菌五个谱系的代表性研究,以产生更相关、更广泛的意义和有效性的数据。

概述

由于缺乏有效的治疗方法,消除对易感个体造成致命感染的假丝酵母菌耳念珠菌极其困难。有希望的新抗真菌药物和策略正在开发中,进一步的改进将促进它们在不久的将来在临床上的使用。

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