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艾沙康唑用于治疗侵袭性曲霉病和毛霉病:当前证据、安全性、疗效及临床建议

Isavuconazole for the treatment of invasive aspergillosis and mucormycosis: current evidence, safety, efficacy, and clinical recommendations.

作者信息

Natesan Suganthini Krishnan, Chandrasekar Pranatharthi H

机构信息

Division of Infectious Diseases, Department of Internal Medicine, Wayne State University; John D Dingell VA Medical Center, Detroit, MI, USA.

Division of Infectious Diseases, Department of Internal Medicine, Wayne State University.

出版信息

Infect Drug Resist. 2016 Dec 7;9:291-300. doi: 10.2147/IDR.S102207. eCollection 2016.

Abstract

The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA) and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles. Polyenes including lipid formulations pose a problem with infusion-related side effects, electrolyte imbalance, and nephrotoxicity. Echinocandins are ineffective against mucorales and are approved as salvage therapy for refractory IA. Given that all available antifungal agents have limitations, there has been an unmet need for a broad-spectrum anti-mold agent with a favorable profile. Following phase III clinical trials that started in 2006, isavuconazole (ISZ) seems to fit this profile. It is the first novel triazole agent recently approved by the United States Food and Drug Administration (FDA) for the treatment of both IA and mucormycosis. This review provides a brief overview of the salient features of ISZ, its favorable profile with regard to spectrum of antifungal activity, pharmacokinetic and pharmacodynamic parameters, drug interactions and tolerability, clinical efficacy, and side effects.

摘要

在免疫功能低下的癌症患者中诊断出的大多数侵袭性霉菌感染包括侵袭性曲霉病(IA)和毛霉病。尽管进行了及时有效的治疗,但死亡率仍然很高。目前可用于治疗这些严重感染的抗真菌药物包括三唑类、多烯类和棘白菌素类。直到最近,泊沙康唑一直是唯一一种对曲霉属和毛霉目均具有广谱抗霉菌活性的三唑类药物。其他临床上可用的三唑类药物伏立康唑和伊曲康唑,对毛霉目活性较差,除了具有所有三唑类药物固有的副作用外,还存在显著的药物相互作用。包括脂质制剂在内的多烯类药物存在与输注相关的副作用、电解质失衡和肾毒性问题。棘白菌素类药物对毛霉目无效,被批准作为难治性IA的挽救治疗药物。鉴于所有可用的抗真菌药物都有局限性,因此一直需要一种具有良好特性的广谱抗霉菌药物。在2006年开始的III期临床试验之后,艾沙康唑(ISZ)似乎符合这一特性。它是美国食品药品监督管理局(FDA)最近批准的第一种用于治疗IA和毛霉病的新型三唑类药物。本综述简要概述了ISZ的显著特征,及其在抗真菌活性谱、药代动力学和药效学参数、药物相互作用和耐受性、临床疗效以及副作用方面的良好特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc54/5153275/2b7a44539ed0/idr-9-291Fig1.jpg

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