瑞扎芬净治疗难治性曲霉感染的真实世界应用

文献信息

中文摘要

背景： 曲霉感染可能带来重大治疗挑战，部分原因是三唑类耐药性不断增加。需要临床见解来了解瑞扎芬净（一种每周给药一次的新一代棘白菌素）在解决当前曲霉感染治疗某些局限性方面的潜力。
方法： 本回顾性病例系列收集了来自八名接受每周一次瑞扎芬净治疗难治性曲霉感染的成人的匿名真实世界数据。这些病例由西班牙、英国和意大利在治疗难治性真菌感染方面具有丰富经验的临床医生提供。
结果： 大多数患者患有肺曲霉病，几乎所有患者三唑类方案治疗失败或不耐受，一半患者既往曾暴露于棘白菌素或两性霉素B。瑞扎芬净主要用于实现门诊肠外抗菌治疗（OPAT），在唑类耐药或不耐受的情况下避免每日静脉注射棘白菌素的需要。约一半患者接受瑞扎芬净单药治疗；其他患者接受联合方案。大多数病例观察到临床和/或影像学改善或疾病稳定，包括唑类耐药感染患者。值得注意的是，一名患者慢性中耳炎得到缓解，其他患者培养转阴或获得持续临床获益。瑞扎芬净耐受性良好，包括肾功能损害患者。一名慢性曲霉球患者接受瑞扎芬净未能获得充分的症状控制，需要手术。
结论： 本报告提供了关于瑞扎芬净作为难治性曲霉感染潜在选择的首批临床见解。在这一有限的患者群体中，瑞扎芬净使OPAT成为可能，促进了出院，并提供了具有临床意义的改善，包括疾病长期稳定和缓解，值得在临床试验中进一步研究。

英文摘要

BACKGROUND: Aspergillus infections can pose significant treatment challenges, due in part to increasing triazole resistance. Clinical insight is needed to understand the potential for rezafungin, a next-generation echinocandin with once-weekly dosing, to address some limitations of current treatments for Aspergillus infections.
METHODS: This retrospective case series collected anonymized real-world data from eight adults who received once-weekly rezafungin for difficult-to-treat Aspergillus infections. The cases were provided by clinicians in Spain, the UK, and Italy with considerable experience in treating challenging fungal infections.
RESULTS: Most patients had pulmonary aspergillosis, nearly all had failed or were intolerant to triazole-based regimens, and half had prior echinocandin or amphotericin B exposure. Rezafungin was used primarily to enable outpatient parenteral antimicrobial therapy (OPAT), avoiding the need for daily IV echinocandin in settings of azole resistance or intolerance. About half received rezafungin as monotherapy; others had combination regimens. Clinical and/or radiological improvement or disease stabilization was observed in most cases, including in patients with azole-resistant infections. Notably, one patient achieved resolution of chronic otitis media, and others had negative cultures or sustained clinical benefit. Rezafungin was well tolerated, including in patients with renal impairment. One patient with chronic aspergilloma did not achieve adequate symptomatic control with rezafungin and required surgery.
CONCLUSIONS: This report provides initial clinical insights on rezafungin as a potential option for difficult-to-treat Aspergillus infections. In this limited group of patients, rezafungin enabled OPAT, facilitated hospital discharge, and provided clinically meaningful improvements, including prolonged disease stabilization and resolution, which merit further investigation in clinical trials.