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实体器官移植受者侵袭性霉菌感染的药物治疗管理。

Pharmacological management of invasive mold infections in solid organ transplant recipients.

机构信息

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain.

出版信息

Expert Opin Pharmacother. 2024 Feb;25(3):239-254. doi: 10.1080/14656566.2024.2326507. Epub 2024 Mar 11.

Abstract

INTRODUCTION

Solid organ transplant (SOT) recipients face an increased susceptibility to invasive fungal infection (IFI) due to filamentous fungi. Post-transplant invasive aspergillosis (IA) and mucormycosis are related to exceedingly high mortality rates and graft loss risk, and its management involve a unique range of clinical challenges.

AREAS COVERED

First, the current treatment recommendations for IA and mucormycosis among SOT recipients are critically reviewed, including the supporting evidence. Next, we discussed particular concerns in this patient population, such as drug-drug interactions (DDIs) between triazoles and post-transplant immunosuppression or treatment-related toxicity. The role for immunomodulatory and host-targeted therapies is also considered, as well as the theoretical impact of the intrinsic antifungal activity of calcineurin inhibitors. Finally, a personal opinion is made on future directions in the pharmacological approach to post-transplant IFI.

EXPERT OPINION

Despite relevant advances in the treatment of mold IFIs in the SOT setting, such as the incorporation of isavuconazole (with lower incidence of DDIs and better tolerability than voriconazole), there remains a large room for improvement in areas such as the position of combination therapy or the optimal strategy for the reduction of baseline immunosuppression. Importantly, future studies should define the specific contribution of newer antifungal agents and classes.

摘要

简介

由于丝状真菌的存在,实体器官移植(SOT)受者易发生侵袭性真菌感染(IFI)。移植后侵袭性曲霉病(IA)和毛霉病与极高的死亡率和移植物丢失风险相关,其治疗涉及一系列独特的临床挑战。

涵盖领域

首先,我们批判性地回顾了 SOT 受者中 IA 和毛霉病的当前治疗建议,包括支持证据。其次,我们讨论了此类患者人群的特殊关注点,例如三唑类药物与移植后免疫抑制之间的药物-药物相互作用(DDI)或与治疗相关的毒性。还考虑了免疫调节和宿主靶向治疗的作用,以及钙调神经磷酸酶抑制剂固有抗真菌活性的理论影响。最后,对移植后 IFI 的药理学治疗方法的未来方向提出了个人意见。

专家意见

尽管在 SOT 环境中治疗霉菌 IFI 方面取得了相关进展,例如伊曲康唑(DDI 发生率较低,耐受性优于伏立康唑)的应用,但在联合治疗的地位或降低基础免疫抑制的最佳策略等方面仍有很大的改进空间。重要的是,未来的研究应确定新型抗真菌药物和类别的具体贡献。

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