QT interval prolongation and cardiotoxicity in shorter regimens for rifampicin-resistant tuberculosis
OBJECTIVES: Effective rifampicin-resistant tuberculosis (RR-TB) regimens often include multiple QT-prolonging drugs, necessitating evaluation across different combinations. METHODS: Using pooled electrocardiogram data from two trials, three QT-prolonging shorter regimens for RR-TB were studied: the injectable-containing regimen comprising moxifloxacin and clofazimine (Mfx/Cfz), a levofloxacin-based regimen with clofazimine (Lfx/Cfz), and a bedaquiline-containing regimen with clofazimine (Bdq/Cfz). The prevalence and severity of corrected QT interval (QTc) prolongation between regimens were compared, and risk factors were evaluated. RESULTS: Among 410 RR-TB participants, significant QTc prolongation was reported in 48.4% (78/161) of participants receiving the Mfx/Cfz regimen, 31.1% (51/164) receiving the Lfx/Cfz regimen, and 34.1% (29/85) receiving the Bdq/Cfz regimen. Nearly half of the significant QTc prolongation events occurred within 4 months of treatment. Seven episodes of symptomatic arrhythmia were documented. Compared with the Lfx/Cfz regimen, the Mfx/Cfz regimen was associated with an increased risk of significant QTc prolongation (adjusted hazard ratio 1.45, 95% confidence interval 1.01-2.07, P = 0.044). Additionally, pre-existing thyroid disease, cavitation, and older age were identified as independent risk factors of significant QTc prolongation. CONCLUSION: The Mfx/Cfz combination was associated with an elevated risk of QTc prolongation. Close electrocardiogram monitoring throughout the entire treatment course is advised in patients receiving such combination.
Authors
- Yilin Zhang
- Yungui Zhang (ORCID: https://orcid.org/0009-0005-2509-2460)
- Mingying Xiao (ORCID: https://orcid.org/0000-0002-2271-0068)
- Feng Sun (ORCID: https://orcid.org/0009-0000-5287-7881)
- Yena Zhang
- Shun Yi Feng (ORCID: https://orcid.org/0000-0002-6114-7837)
- Yiming Li (ORCID: https://orcid.org/0000-0002-6107-5618)
- Cui Cai
- Jichan Shi
- Ya Huang
- Zebao He
- Yuan Qian (ORCID: https://orcid.org/0000-0001-6361-8033)
- Yuqing Wu
- Hengzhong Yi
- Haiqing Liu
- Hua Wang
- Jing Wang
- Wenhong Zhang
- Yuanbo Lan
- Yuanyuan Chen
- Qianhong Wu
- Hongying Yu
- Yong Zhou
Institutions
- Huaihua University (CN)
- Zunyi Medical University (CN)
- Wenzhou Medical University (CN)
- Jinyintan Hospital (CN)
- Kunming Third People's Hospital (CN)
- Wenzhou Central Hospital (CN)
- Ningbo No. 2 Hospital (CN)
- Shanghai Public Health Clinical Center (CN)
- Heilongjiang Center for Tuberculosis Control and Prevention (CN)
- Jiangxi Chest Hospital (CN)
- The People's Hospital of Guangxi Zhuang Autonomous Region (CN)
- Anhui Provincial Hospital (CN)
- Hunan Province Chest Hospital (CN)
- Liupanshui Normal University (CN)
- Puer University (CN)
- Baoshan University (CN)
- Hangzhou Red Cross Hospital (CN)
- General Electric (Norway) (NO)
- The First People's Hospital of Zhaoqing (CN)
- Huashan Hospital (CN)
- Yunnan Provincial Infectious Disease Hospital (CN)
- Ningbo No.6 Hospital (CN)
- Fuyang Second People's Hospital (CN)
Publication Details
- Journal
- International Journal of Infectious Diseases
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1016/j.ijid.2026.108661
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Science and Technology Commission of Shanghai Municipality
- Shanghai Hospital Development Center
- Shanghai Shenkang Hospital Development Center
- National Science and Technology Major Project
- National Major Science and Technology Projects of China