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丝状真菌抗真菌药物耐药性的分子基础。

Molecular bases of antifungal resistance in filamentous fungi.

机构信息

Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110 007, India.

Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110 007, India.

出版信息

Int J Antimicrob Agents. 2017 Nov;50(5):607-616. doi: 10.1016/j.ijantimicag.2017.06.018. Epub 2017 Jul 10.

Abstract

Invasive mould infections due to Aspergillus spp., Fusarium spp., Scedosporium spp. and other filamentous fungi remain a significant cause of morbidity and mortality in immunocompromised patients. Antifungal therapy is required for successful patient management; however, limited antifungal drugs as well as the emergence of drug resistance pose a challenge to clinicians for effective management of these diseases. The evolution of multidrug-resistant strains owing to selective pressure as well as intrinsically-resistant pathogenic species are a major concern. Thus, it is necessary to gain a better insight into the antifungal resistance mechanisms and their clinical impact. So far, the resistance mechanisms responsible for acquired azole resistance include alteration of the drug target and its overexpression, biofilm formation and efflux pump upregulation. However, mechanisms responsible for polyene and echinocandin resistance are less understood in filamentous moulds, primarily due to incomplete correlation between in vitro susceptibility and clinical response to treatment. The present review gives an insight into the mechanisms implicated in resistance to different classes of antifungal agents both in human and plant pathogenic filamentous fungi. Furthermore, the spectrum of antifungal resistance in these filamentous fungi is highlighted.

摘要

曲霉菌属、镰刀菌属、枝顶孢属和其他丝状真菌引起的侵袭性霉菌感染仍然是免疫功能低下患者发病率和死亡率的重要原因。为了成功治疗患者,需要进行抗真菌治疗;然而,有限的抗真菌药物以及耐药性的出现,给临床医生有效管理这些疾病带来了挑战。由于选择性压力以及固有耐药性致病物种的进化,多药耐药菌株的出现令人担忧。因此,有必要深入了解抗真菌耐药机制及其临床影响。到目前为止,导致获得性唑类耐药的耐药机制包括药物靶点的改变及其过表达、生物膜形成和外排泵上调。然而,由于丝状真菌中对多烯类和棘白菌素类耐药的机制了解较少,主要是因为体外药敏试验与临床治疗反应之间不完全相关。本综述深入探讨了人类和植物病原性丝状真菌中不同类别的抗真菌药物耐药性的相关机制。此外,还强调了这些丝状真菌的抗真菌耐药谱。

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