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异基因造血干细胞移植受者真菌感染的药物治疗进展。

An update on pharmacotherapy for fungal infections in allogeneic stem cell transplant recipients.

机构信息

Pediatric Hematology & Oncology, 4th Department of Pediatrics, Aristotle University School of Medicine and Papageorgiou General Hospital, Thessaloniki, Greece.

Infectious Diseases Unit, 3rd Department of Pediatrics, Aristotle University School of Medicine and Hippokration General Hospital, Thessaloniki, Greece.

出版信息

Expert Opin Pharmacother. 2024 Aug;25(11):1453-1482. doi: 10.1080/14656566.2024.2387686. Epub 2024 Aug 13.

Abstract

INTRODUCTION

Invasive fungal diseases (IFD) constitute a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients.

AREAS COVERED

We describe epidemiology, causes and risk factors of IFD in allogeneic HSCT discussing prophylaxis and treatment in various HSCT phases. We present the most recent studies on this thematic area, including novel data on currently available antifungals, i.e. formulations, dosing, safety, efficacy and therapeutic drug monitoring. Finally, we present the most recent relevant recommendations published. Literature search included PubMed, Scopus, and clinicaltrials.gov between January 2014 and April 2024.

EXPERT OPINION

The antifungal agents employed for prophylaxis and therapy should be predicated on local epidemiology of IFD. Fluconazole prophylaxis remains a first-line choice before engraftment when the main pathogen is spp. After engraftment, prophylaxis should be with mold-active agents (i.e. triazoles). For candidiasis, echinocandins are suggested as first-line treatment, whereas aspergillosis responds well to mold-active azoles and liposomal amphotericin B (L-AmB). For mucormycosis, treatment of choice includes L-AmB and isavuconazole. Choice between fever-driven and diagnostics-driven strategies remains equivocal. Open research topics remain: 1) optimization of tools to ensure prompt and accurate IFD diagnosis to avoid unnecessary exposure to antifungals, drug interactions and cost; 2) refinement of treatment for resistant/refractory strains.

摘要

简介

侵袭性真菌病(IFD)是造血干细胞移植(HSCT)受者发病率和死亡率的主要原因。

涵盖领域

我们描述了异基因 HSCT 中 IFD 的流行病学、病因和危险因素,并讨论了各个 HSCT 阶段的预防和治疗。我们介绍了该主题领域的最新研究,包括目前可用抗真菌药物的新数据,即制剂、剂量、安全性、疗效和治疗药物监测。最后,我们介绍了最新发布的相关建议。文献检索包括 2014 年 1 月至 2024 年 4 月期间的 PubMed、Scopus 和 clinicaltrials.gov。

专家意见

预防和治疗所用的抗真菌药物应基于 IFD 的局部流行病学。在植入前,当主要病原体为 spp. 时,氟康唑预防仍然是首选。植入后,应使用防霉剂(即三唑类)进行预防。对于念珠菌病,建议使用棘白菌素作为一线治疗药物,而曲霉病则对防霉唑类和脂质体两性霉素 B(L-AmB)反应良好。对于毛霉菌病,治疗选择包括 L-AmB 和伊曲康唑。发热驱动和诊断驱动策略之间的选择仍然存在争议。仍存在未解决的研究课题:1)优化工具以确保及时准确地诊断 IFD,避免不必要的抗真菌药物暴露、药物相互作用和成本;2)改进耐药/难治性菌株的治疗方法。

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