Update on Antifungal Drug Resistance.
Update on Antifungal Drug Resistance.
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DOI：
10.1007/s40588-015-0015-1
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发表时间：
2015-06-01
影响因子：
5.2
通讯作者：
Zhao, Yanan
中科院分区：
文献类型：
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作者：
Perlin, David S;Shor, Erika;Zhao, Yanan
侵袭性真菌感染仍然是全球发病率和死亡率的主要来源，特别是在具有潜在免疫抑制的患者中。成功的患者管理需要抗真菌治疗。然而，由于抗真菌药物种类有限以及抗真菌药物耐药性的出现，治疗选择受到限制。在某些情况下，对几类抗真菌药物不敏感的多重耐药菌株的进化是一个主要问题。导致获得性耐药的耐药机制已得到很好的表征，包括药物靶点亲和力和丰度的变化，以及生物膜和外排泵导致的细胞内药物水平的降低。高水平和多药耐药性的发展是通过不同机制的逐步演变而发生的。影响这些机制的遗传因素正在出现，它们形成了细胞相互作用的复杂交响曲，使细胞能够适应和/或克服药物引起的应激。耐药性的驱动因素涉及宿主和微生物因素的复杂结合。了解这些机制将有助于开发更好的诊断和治疗策略，以克服和预防抗真菌耐药性。
Invasive fungal infections remain a major source of global morbidity and mortality, especially among patients with underlying immune suppression. Successful patient management requires antifungal therapy. Yet, treatment choices are restricted due to limited classes of antifungal agents and the emergence of antifungal drug resistance. In some settings, the evolution of multidrug-resistant strains insensitive to several classes of antifungal agents is a major concern. The resistance mechanisms responsible for acquired resistance are well characterized and include changes in drug target affinity and abundance, and reduction in the intracellular level of drug by biofilms and efflux pumps. The development of high-level and multidrug resistance occurs through a stepwise evolution of diverse mechanisms. The genetic factors that influence these mechanisms are emerging and they form a complex symphony of cellular interactions that enable the cell to adapt and/or overcome drug-induced stress. Drivers of resistance involve a complex blend of host and microbial factors. Understanding these mechanisms will facilitate development of better diagnostics and therapeutic strategies to overcome and prevent antifungal resistance.