伏立康唑联合特比萘芬联合抗真菌治疗侵袭性繁茂枝孢菌感染：2008-2019 年 FungiScope®登记处 41 例患者分析。

Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019.

机构信息

Department of Medicine, University of California San Diego, San Diego, CA, USA; Clinical and Translational Fungal Research Group, University of California San Diego, San Diego, CA, USA.

Department I of Internal Medicine, ECMM Excellence Centre of Medical Mycology, CECAD-Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital Cologne, Cologne, Germany.

出版信息

Clin Microbiol Infect. 2020 Jun;26(6):784.e1-784.e5. doi: 10.1016/j.cmi.2020.01.012. Epub 2020 Jan 20.

DOI:10.1016/j.cmi.2020.01.012

PMID:31972317

Abstract

OBJECTIVES

Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections.

METHODS

We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies.

RESULTS

Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days).

CONCLUSIONS

While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.

摘要

目的

繁茂枝梗孢（Lomentospora prolificans）是一种新兴的严重侵袭性真菌感染的病因。尽管含伏立康唑的治疗方案被认为是首选治疗方法，但这些感染的最佳治疗方法尚不清楚。本研究旨在评估联合抗真菌治疗在繁茂枝梗孢感染中的作用。

方法

我们对 2008 年 1 月 1 日至 2019 年 9 月 9 日期间在罕见侵袭性真菌感染真菌学监测器（FungiScope®）登记处确诊的侵袭性繁茂枝梗孢感染患者的病历进行了回顾性分析。我们比较了不同抗真菌治疗策略的临床结局。

结果

在研究期间，FungiScope®登记处共记录了来自 8 个不同国家的 41 例侵袭性繁茂枝梗孢感染患者。总体而言，40 例患者中 17 例（43%）有治疗反应/稳定疾病，21 例（53%）因侵袭性真菌感染而死亡。联合抗真菌治疗与 28 天生存率的提高相关（24 例中 15 例存活，16 例接受单药治疗中 4 例存活；p=0.027），与其他抗真菌治疗方案相比，伏立康唑联合特比萘芬联合治疗的治疗成功率更高（16 例中 10 例，63%，95%CI35%-85%）（24 例中 7 例，29%，95%CI13%-51%，p=0.053）。在 Kaplan-Meier 生存分析中，接受伏立康唑/特比萘芬联合治疗的个体的生存概率高于其他抗真菌治疗方案（中位生存时间 150 天与 17 天）。