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膦甲酸钠治疗免疫功能低下患者阿昔洛韦耐药性黏膜皮肤单纯疱疹的疗效和毒性多中心评估

A Multicenter Assessment of the Outcomes and Toxicities of Foscarnet for Treatment of Acyclovir-Resistant Mucocutaneous Herpes Simplex in Immunocompromised Patients.

作者信息

Hammond Sarah P, Rangaraju Manickam, Sumner Melanie, Timmler Burkhard, Chandrasekar Pranatharthi, Avery Robin K

机构信息

Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.

AiCuris Anti-infective Cures AG, Wuppertal, Germany.

出版信息

Open Forum Infect Dis. 2024 Feb 5;11(3):ofae046. doi: 10.1093/ofid/ofae046. eCollection 2024 Mar.

Abstract

BACKGROUND

Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection is an uncommon problem typically seen in immunocompromised hosts. Systemic treatment options are limited. The performance of foscarnet and its toxicities in this population are poorly characterized.

METHODS

This was a multicenter retrospective study of adults treated with foscarnet for HSV infection between January 2012 and December 2017. Relevant data were collected including demographics, baseline conditions, previous anti-HSV medications, concomitant medications, HSV outcomes, and adverse events. Acyclovir-resistant HSV infection was defined based on genotypic or phenotypic testing results; refractory infection was defined as infection not improving after 5 days of treatment-dosed antiviral therapy in those not tested for resistance.

RESULTS

Twenty-nine patients had 31 episodes of HSV (15/18 resistant; among episodes without resistance testing, 7/10 refractory; 3 not evaluable) treated with foscarnet. All patients were immunocompromised including 19 (66%) with hematologic malignancy and 9 (31%) with HIV. Median duration of foscarnet was 16 days (range, 6-85 days). Fifteen episodes (48%) healed by the end of or after foscarnet. Median time to healing among those with resolution was 38 days (range, 9-1088 days). At least 1 adverse event during therapy was reported in 26 (84%) treatment episodes including 23 (74%) that were considered drug related. Common adverse events were electrolyte disturbance (20 [65%]) and kidney dysfunction (13 [42%]). Foscarnet was discontinued in 10 episodes (32%) due to an adverse event, including 6 due to kidney dysfunction.

CONCLUSIONS

Among 31 episodes of HSV treated with foscarnet, only half resolved with treatment, and adverse events were common.

摘要

背景

耐阿昔洛韦的皮肤黏膜单纯疱疹病毒(HSV)感染是一个不常见的问题,通常见于免疫功能低下的宿主。全身治疗选择有限。膦甲酸钠在该人群中的疗效及其毒性特征尚不明确。

方法

这是一项多中心回顾性研究,研究对象为2012年1月至2017年12月期间接受膦甲酸钠治疗HSV感染的成人。收集了相关数据,包括人口统计学资料、基线状况、既往抗HSV药物、合并用药、HSV治疗结果及不良事件。耐阿昔洛韦的HSV感染根据基因型或表型检测结果定义;难治性感染定义为在未进行耐药性检测的患者中,经过5天治疗剂量的抗病毒治疗后感染仍无改善。

结果

29例患者接受了31次膦甲酸钠治疗的HSV感染发作(15/18例耐药;在未进行耐药性检测的发作中,7/10例难治性;3例无法评估)。所有患者均免疫功能低下,其中19例(66%)患有血液系统恶性肿瘤,9例(31%)感染HIV。膦甲酸钠的中位治疗时间为16天(范围6 - 85天)。15次发作(48%)在膦甲酸钠治疗结束时或之后愈合。愈合患者的中位愈合时间为38天(范围9 - 1088天)。26次(84%)治疗发作报告了至少1次治疗期间的不良事件,其中23次(74%)被认为与药物相关。常见不良事件为电解质紊乱(20例[65%])和肾功能不全(13例[42%])。10次发作(32%)因不良事件停用膦甲酸钠,其中6次因肾功能不全停用。

结论

在接受膦甲酸钠治疗的31次HSV感染发作中,仅半数经治疗后缓解,且不良事件常见。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b33/10914364/01f8dc92d296/ofae046_ga.jpg

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