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新型三唑类抗真菌剂。

Novel triazole antifungal agents.

作者信息

Hoffman H L, Ernst E J, Klepser M E

机构信息

University of Iowa, S412 Pharmacy Building, Iowa City, IA 52242-1112, USA.

出版信息

Expert Opin Investig Drugs. 2000 Mar;9(3):593-605. doi: 10.1517/13543784.9.3.593.

Abstract

The risk of opportunistic infections is greatly increased in patients who are immunocompromised due to AIDS, cancer chemotherapy and organ or bone marrow transplantation. Candida albicans is often associated with serious systemic fungal infections, however other Candida species such as Candida krusei, Candida tropicalis and Candida glabrata, as well as Cryptococcus neoformans and filamentous fungi such as Aspergillus, have also emerged as clinically significant fungal pathogens. Two triazole antifungal agents, fluconazole and itraconazole, were introduced over a decade ago and since then have been used extensively for the prophylaxis and treatment of a variety of fungal infections. Although both drugs are effective and have their place in therapy, limitations regarding the utility of these agents do exist. For example, fluconazole is not effective for the prophylaxis or treatment of Aspergillus species and has limited activity against C. krusei and C. glabrata. The use of itraconazole has been limited secondary to concerns regarding unpredictable bioavailability. The rising incidence of fungal infections and the reported increase of non-albicans candidal infections noted over the past two decades highlight the need for new antifungal agents with improved spectra of activity. Several new triazole agents are in various phases of preclinical and clinical trials and may be available for human use in the near future. Three such agents voriconazole, posaconazole and ravuconazole are reviewed and compared with existing agents.

摘要

由于艾滋病、癌症化疗以及器官或骨髓移植而导致免疫功能低下的患者,发生机会性感染的风险会大幅增加。白色念珠菌常与严重的系统性真菌感染相关,然而其他念珠菌属,如克柔念珠菌、热带念珠菌和光滑念珠菌,以及新型隐球菌和丝状真菌(如曲霉菌),也已成为具有临床意义的真菌病原体。两种三唑类抗真菌药物,氟康唑和伊曲康唑,在十多年前就已问世,自那时起已被广泛用于预防和治疗各种真菌感染。尽管这两种药物都有效且在治疗中占有一席之地,但这些药物的效用确实存在局限性。例如,氟康唑对曲霉菌的预防或治疗无效,对克柔念珠菌和光滑念珠菌的活性有限。由于对其不可预测的生物利用度存在担忧,伊曲康唑的使用受到限制。在过去二十年中,真菌感染发病率的上升以及非白色念珠菌感染报告病例的增加,凸显了对具有更广泛活性谱的新型抗真菌药物的需求。几种新型三唑类药物正处于临床前和临床试验的不同阶段,可能在不久的将来可供人类使用。本文对伏立康唑、泊沙康唑和雷夫康唑这三种此类药物进行了综述,并与现有药物进行了比较。

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