Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.
Med Mycol. 2019 Jun 1;57(Supplement_3):S328-S343. doi: 10.1093/mmy/myz012.
The high burden and growing prevalence of invasive fungal infections (IFIs), the toxicity and interactions associated with current antifungal drugs, as well as the increasing resistance, ask for the development of new antifungal drugs, preferably with a novel mode of action. Also, the availability of oral or once-weekly alternatives would enable ambulatory treatment resulting in an improved patient's comfort and therapy adherence. However, only one new azole and two new posaconazole-formulations were marketed over the last decade. This review focuses on the antifungal drugs in the pipeline undergoing clinical evaluation. First, the newest azole, isavuconazole, with its improved safety profile and reduction in DDIs, will be discussed. Moreover, there are two glucan synthase inhibitors (GSIs) in the antifungal pipeline: rezafungin (CD101), a long-acting echinocandin with an improved stability that enables once weekly administration, and SCY-078, an orally available GSI with efficacy against azole- and echinocandin resistant isolates. A new oral formulation of amphotericin B will also be presented. Moreover, the first representative of a new antifungal class, the orotomides, with a broad spectrum and no cross-resistance with current antifungal classes, will be discussed. Finally, an overview of other antifungals that are still in earlier clinical development phases, is provided.
侵袭性真菌感染（IFI）的负担高且呈上升趋势，目前抗真菌药物存在毒性和相互作用，以及耐药性不断增加，这都要求开发新的抗真菌药物，最好具有新的作用模式。此外，口服或每周一次的替代品的出现将能够进行门诊治疗，从而提高患者的舒适度和治疗依从性。然而，在过去十年中，仅有一种新型唑类药物和两种新型泊沙康唑制剂上市。本综述重点介绍了正在进行临床评估的抗真菌药物。首先，将讨论新型唑类药物伊曲康唑，其具有更好的安全性和减少药物相互作用的特点。此外，抗真菌药物研发管道中有两种葡聚糖合成酶抑制剂（GSIs）：rezafungin（CD101），一种长效棘白菌素，稳定性提高，可每周给药一次，以及 SCY-078，一种口服可用的 GSI，对唑类和棘白菌素耐药株有效。还将介绍一种新的两性霉素 B 口服制剂。此外，将讨论第一个新型抗真菌类别的代表物——otomides，其具有广谱性，与目前的抗真菌类别无交叉耐药性。最后，提供了其他仍处于早期临床开发阶段的抗真菌药物的概述。
