Treatment strategies for cryptococcal infection: challenges, advances and future outlook.
Treatment strategies for cryptococcal infection: challenges, advances and future outlook.
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DOI：
10.1038/s41579-021-00511-0
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Cowen LE
中科院分区：
文献类型：
--
作者：
Iyer KR;Revie NM;Fu C;Robbins N;Cowen LE
隐球菌属，特别是新型隐球菌和格特隐球菌，对全世界人类健康具有巨大影响。隐球菌性脑膜炎的全球负担接近每年 25 万病例和 181,000 人死亡，如果感染不及时治疗，死亡率为 100%。尽管有这些令人震惊的统计数据，隐球菌病的治疗选择仍然有限，只有三类主要药物被批准用于临床。加剧公共卫生负担的事实是，几十年来开发的唯一一类新型抗真菌药物棘白菌素，对隐球菌属的抗真菌活性可以忽略不计，而其余疗法的功效受到宿主毒性和病原体耐药性的阻碍。在这里，我们描述了当前的抗真菌药物库以及用于控制隐球菌疾病的治疗策略。我们进一步阐述了我们对隐球菌属所利用的内在和适应性耐药机制的理解的最新进展。逃避治疗。最后，我们回顾了潜在的治疗策略，包括联合治疗、针对毒力特征、损害应激反应途径和调节宿主免疫，以有效治疗隐球菌引起的感染。总体而言，对调节抗隐球菌耐药性机制的了解，加上基因组学技术和高通量筛选方法的进步，将促进创新并加速抗真菌药物的发现。隐球菌病是一种严重的真菌感染，治疗选择有限。在这篇综述中，Cowen 和同事讨论了当前可用于隐球菌感染的抗真菌治疗、开发新疗法的挑战以及寻找新疗法的持续努力。
Cryptococcus spp., in particular Cryptococcus neoformans and Cryptococcus gattii, have an enormous impact on human health worldwide. The global burden of cryptococcal meningitis is almost a quarter of a million cases and 181,000 deaths annually, with mortality rates of 100% if infections remain untreated. Despite these alarming statistics, treatment options for cryptococcosis remain limited, with only three major classes of drugs approved for clinical use. Exacerbating the public health burden is the fact that the only new class of antifungal drugs developed in decades, the echinocandins, displays negligible antifungal activity against Cryptococcus spp., and the efficacy of the remaining therapeutics is hampered by host toxicity and pathogen resistance. Here, we describe the current arsenal of antifungal agents and the treatment strategies employed to manage cryptococcal disease. We further elaborate on the recent advances in our understanding of the intrinsic and adaptive resistance mechanisms that are utilized by Cryptococcus spp. to evade therapeutic treatments. Finally, we review potential therapeutic strategies, including combination therapy, the targeting of virulence traits, impairing stress response pathways and modulating host immunity, to effectively treat infections caused by Cryptococcus spp. Overall, understanding of the mechanisms that regulate anti-cryptococcal drug resistance, coupled with advances in genomics technologies and high-throughput screening methodologies, will catalyse innovation and accelerate antifungal drug discovery. Cryptococcosis is a serious fungal infection for which treatment options are limited. In this Review, Cowen and colleagues discuss the current antifungal treatments available for cryptococcal infections, the challenges in developing new treatments, and ongoing efforts to identify novel therapies.
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