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恰加斯病的抗锥虫治疗:单中心关于药物不良反应及提高治疗完成率策略的经验

Antitrypanosomal therapy for Chagas disease: A single center experience with adverse drug reactions and strategies for enhancing treatment completion.

作者信息

Reifler Katherine, Wheelock Alyse, Hall Samantha M, Dauphinais Madolyn, Roytburd Samuel, Maiullari Michael, Salazar Alejandra, Maldonado Ashley, West Helen Mahoney, Köhler Julia R, Barnett Elizabeth D, Gopal Deepa M, Hamer Davidson H, Bourque Daniel L

机构信息

Section of Infectious Disease, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States of America.

Section of Preventative Medicine and Epidemiology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States of America.

出版信息

PLoS Negl Trop Dis. 2025 Jul 7;19(7):e0013218. doi: 10.1371/journal.pntd.0013218. eCollection 2025 Jul.

Abstract

Anti-trypanosomal therapy is generally recommended for individuals under age 50 with the indeterminate form of Chagas disease to prevent disease progression. However, benznidazole and nifurtimox are associated with adverse drug reactions. We performed a retrospective review of treatment tolerability among patients with Chagas disease referred to Boston Medical Center from June 2016 to June 2024. There were 125 individuals evaluated, of whom 32 (25.6%) had contraindications to and 2 (1.6%) declined antiparasitic treatment. Ninety-one started therapy (83 with benznidazole, 8 with nifurtimox) with monitoring co-managed by infectious diseases physicians and pharmacists. Following benznidazole initiation, 70 (84.3%) had at least one adverse event, of which allergic (39/83, 47.0%), gastrointestinal (38/83, 45.8%), and neuropsychiatric (33/83, 39.8%) reactions were most common. Rash led to treatment discontinuation in 19 patients (22.9%) and met criteria for grade 3 severity in 13 (15.7%). Adjunctive therapies for rash included topical and systemic steroids and systemic antihistamines. Peripheral neuropathy led to treatment cessation for 13 patients (15.7%). Gastrointestinal adverse effects occurred in 38 patients (45.8%), were relatively mild, and managed with H2 blockers or proton pump inhibitors. Thirty (36.1%) patients were unable to complete 60 days of benznidazole, of whom 15 switched to nifurtimox. Eight patients started with nifurtimox during a benznidazole shortage. Nifurtimox was more frequently associated with gastrointestinal side effects (21/23, 91.3%) compared to benznidazole. Ultimately, 83 patients (91.2%) received at least 30 days, and 68 patients (74.7%) completed at least 60 days of benznidazole or nifurtimox. Multiple strategies were used to prevent and alleviate adverse events; multi-disciplinary team management was essential. These findings underscore the support needed for individuals with Chagas disease to tolerate and complete therapy and highlight the need for safer and more effective options to facilitate access to treatment.

摘要

对于年龄在50岁以下、患有查加斯病不确定型的个体,通常建议进行抗锥虫治疗以预防疾病进展。然而,苯并硝唑和硝呋替莫与药物不良反应有关。我们对2016年6月至2024年6月转诊至波士顿医疗中心的查加斯病患者的治疗耐受性进行了回顾性研究。共评估了125名个体,其中32人(25.6%)有抗寄生虫治疗的禁忌症,2人(1.6%)拒绝接受抗寄生虫治疗。91人开始治疗(83人使用苯并硝唑,8人使用硝呋替莫),由传染病医生和药剂师共同进行监测。开始使用苯并硝唑后,70人(84.3%)至少出现了一次不良事件,其中过敏反应(39/83,47.0%)、胃肠道反应(38/83,45.8%)和神经精神反应(33/83,39.8%)最为常见。皮疹导致19名患者(22.9%)停药,13名患者(15.7%)的皮疹符合3级严重程度标准。皮疹的辅助治疗包括局部和全身使用类固醇以及全身使用抗组胺药。周围神经病变导致13名患者(15.7%)停药。38名患者(45.8%)出现胃肠道不良反应,症状相对较轻,通过使用H2阻滞剂或质子泵抑制剂进行处理。30名患者(36.1%)无法完成60天的苯并硝唑治疗,其中15人改用硝呋替莫。在苯并硝唑短缺期间,8名患者开始使用硝呋替莫。与苯并硝唑相比,硝呋替莫更常出现胃肠道副作用(21/23,91.3%)。最终,83名患者(91.2%)接受了至少30天的治疗,68名患者(74.7%)完成了至少60天的苯并硝唑或硝呋替莫治疗。我们采用了多种策略来预防和减轻不良事件;多学科团队管理至关重要。这些发现强调了查加斯病患者耐受并完成治疗所需的支持,并突出了需要更安全、更有效的选择以促进治疗的可及性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f03/12233308/b80a0a99160b/pntd.0013218.g001.jpg

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