Spitzer Michaela, Robbins Nicole, Wright Gerard D
a Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences , McMaster University , Hamilton , ON , Canada.
Virulence. 2017 Feb 17;8(2):169-185. doi: 10.1080/21505594.2016.1196300. Epub 2016 Jun 7.
Invasive fungal infections are an important cause of human mortality and morbidity, particularly for immunocompromised populations. However, there remains a paucity of antifungal drug treatments available to combat these fungal pathogens. Further, antifungal compounds are plagued with problems such as host toxicity, fungistatic activity, and the emergence of drug resistance in pathogen populations. A promising therapeutic strategy to increase drug effectiveness and mitigate the emergence of drug resistance is through the use of combination drug therapy. In this review we describe the current arsenal of antifungals in medicine and elaborate on the benefits of combination therapy to expand our current antifungal drug repertoire. We examine those antifungal combinations that have shown potential against fungal pathogens and discuss strategies being employed to discover novel combination therapeutics, in particular combining antifungal agents with non-antifungal bioactive compounds. The findings summarized in this review highlight the promise of combinatorial strategies in combatting invasive mycoses.
侵袭性真菌感染是导致人类发病和死亡的重要原因,对免疫功能低下人群尤为如此。然而,目前用于对抗这些真菌病原体的抗真菌药物治疗方法仍然匮乏。此外,抗真菌化合物存在诸多问题,如宿主毒性、抑菌活性以及病原体群体中耐药性的出现。一种有望提高药物疗效并减轻耐药性出现的治疗策略是采用联合药物疗法。在这篇综述中,我们描述了医学中当前的抗真菌药物库,并详细阐述联合疗法的益处,以扩充我们目前的抗真菌药物种类。我们研究了那些已显示出对真菌病原体有潜力的抗真菌联合用药,并讨论了用于发现新型联合疗法的策略,特别是将抗真菌剂与非抗真菌生物活性化合物联合使用的策略。这篇综述总结的研究结果突出了联合策略在对抗侵袭性真菌病方面的前景。