Martin Genevieve E, Bramwell Joshua, Gadil Eden, Woerle Celeste, Ewin Thomas, Davies Jane, Janson Sonja, Currie Bart J
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia; Infectious Diseases Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia; Department of Infectious Diseases, University of Melbourne, Melbourne, Australia.
Infectious Diseases Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
Int J Infect Dis. 2025 Jan;150:107283. doi: 10.1016/j.ijid.2024.107283. Epub 2024 Nov 8.
Trimethoprim/sulfamethoxazole is the first-line agent for oral eradication therapy for melioidosis but has been associated with toxicity in this context. This study aimed to quantify adverse drug reactions (ADRs) to trimethoprim/sulfamethoxazole when used for treatment of melioidosis, and assess risk factors for ADR development. A retrospective review of antimicrobial associated ADRs was performed in all patients treated for melioidosis in the Northern Territory of Australia from January 2017-September 2022. Over this time, 268 treatment episodes from 256 individuals were included. The frequency of clinician-attributed ADRs to trimethoprim/sulfamethoxazole (51% of exposed) was higher than for other antimicrobials used (ceftazidime 12%, meropenem 8%, and doxycycline 12% of those exposed; P < 0.0001). 44% of those treated with trimethoprim/sulfamethoxazole required drug cessation or dose reduction and 5 individuals (2%) had a severe cutaneous adverse reaction, with one fatality. Acute kidney injury was the most frequent ADR (25% of those exposed), with age and pre-existing renal disease independently associated with its development. Here we report very high rates of ADRs attributed to trimethoprim/sulfamethoxazole resulting in frequent discontinuation of this drug as part of oral eradication therapy for melioidosis. Further work is needed to balance the necessity and toxicity of this drug in this clinical context.
甲氧苄啶/磺胺甲恶唑是类鼻疽病口服根除治疗的一线药物，但在此情况下与毒性有关。本研究旨在量化甲氧苄啶/磺胺甲恶唑用于治疗类鼻疽病时的药物不良反应（ADR），并评估ADR发生的风险因素。对2017年1月至2022年9月在澳大利亚北领地接受类鼻疽病治疗的所有患者的抗菌药物相关ADR进行了回顾性分析。在此期间，纳入了256名个体的268个治疗疗程。临床医生归因于甲氧苄啶/磺胺甲恶唑的ADR发生率（暴露者的51%）高于其他使用的抗菌药物（头孢他啶为暴露者的12%，美罗培南为8%，多西环素为12%；P<0.0001）。接受甲氧苄啶/磺胺甲恶唑治疗的患者中有44%需要停药或减量，5名患者（2%）出现严重皮肤不良反应，其中1例死亡。急性肾损伤是最常见的ADR（暴露者的25%），年龄和既往肾病与其发生独立相关。在此我们报告，作为类鼻疽病口服根除治疗的一部分，归因于甲氧苄啶/磺胺甲恶唑的ADR发生率非常高，导致该药物频繁停用。在这种临床情况下，需要进一步开展工作以平衡该药物的必要性和毒性。
