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念珠菌中的抗真菌药物耐药性:特别关注两性霉素B。

Antifungal drug resistance in Candida: a special emphasis on amphotericin B.

作者信息

Ahmady Lailema, Gothwal Manisha, Mukkoli Muhammed Mushthaque, Bari Vinay Kumar

机构信息

Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Bathinda, India.

出版信息

APMIS. 2024 May;132(5):291-316. doi: 10.1111/apm.13389. Epub 2024 Mar 11.

Abstract

Invasive fungal infections in humans caused by several Candida species, increased considerably in immunocompromised or critically ill patients, resulting in substantial morbidity and mortality. Candida albicans is the most prevalent species, although the frequency of these organisms varies greatly according to geographic region. Infections with C. albicans and non-albicans Candida species have become more common, especially in the past 20 years, as a result of aging, immunosuppressive medication use, endocrine disorders, malnourishment, extended use of medical equipment, and an increase in immunogenic diseases. Despite C. albicans being the species most frequently associated with human infections, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei also have been identified. Several antifungal drugs with different modes of action are approved for use in clinical settings to treat fungal infections. However, due to the common eukaryotic structure of humans and fungi, only a limited number of antifungal drugs are available for therapeutic use. Furthermore, drug resistance in Candida species has emerged as a result of the growing use of currently available antifungal drugs against fungal infections. Amphotericin B (AmB), a polyene class of antifungal drugs, is mainly used for the treatment of serious systemic fungal infections. AmB interacts with fungal plasma membrane ergosterol, triggering cellular ion leakage via pore formation, or extracting the ergosterol from the plasma membrane inducing cellular death. AmB resistance is primarily caused by changes in the content or structure of ergosterol. This review summarizes the antifungal drug resistance exhibited by Candida species, with a special focus on AmB.

摘要

由几种念珠菌属引起的人类侵袭性真菌感染在免疫功能低下或重症患者中显著增加,导致了相当高的发病率和死亡率。白色念珠菌是最常见的菌种,不过这些微生物的感染频率因地理区域而异。由于老龄化、免疫抑制药物的使用、内分泌紊乱、营养不良、医疗设备的长期使用以及免疫原性疾病的增加,白色念珠菌和非白色念珠菌的感染变得更加普遍,尤其是在过去20年。尽管白色念珠菌是最常与人类感染相关的菌种,但光滑念珠菌、近平滑念珠菌、热带念珠菌和克柔念珠菌也已被确认。几种具有不同作用方式的抗真菌药物已被批准用于临床治疗真菌感染。然而,由于人类和真菌具有共同的真核结构,可供治疗使用的抗真菌药物数量有限。此外,由于目前可用的抗真菌药物越来越多地用于治疗真菌感染,念珠菌属的耐药性已经出现。两性霉素B(AmB)是一种多烯类抗真菌药物,主要用于治疗严重的全身性真菌感染。AmB与真菌细胞膜中的麦角固醇相互作用,通过形成孔道引发细胞离子泄漏,或从细胞膜中提取麦角固醇导致细胞死亡。AmB耐药性主要是由麦角固醇含量或结构的变化引起的。本综述总结了念珠菌属表现出的抗真菌耐药性,特别关注AmB。

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