Selecting an appropriate all-oral short-course regimen for patients with multidrug-resistant or pre-extensive drug-resistant tuberculosis in China: A multicenter prospective cohort study

Liang Fu; Xilin Zhang; Juan Xiong; Feng Sun; Taoping Weng; Yang Li; Peize Zhang; Hui Li; Qianting Yang; Yi Cai; Hancheng Liang; Qiuqi Chen; Zhaoqing Wang; Lei Liu; Xinchun Chen; Wenhong Zhang; Guofang Deng

doi:10.1016/j.ijid.2023.08.001

Selecting an appropriate all-oral short-course regimen for patients with multidrug-resistant or pre-extensive drug-resistant tuberculosis in China: A multicenter prospective cohort study

Int J Infect Dis. 2023 Oct:135:101-108. doi: 10.1016/j.ijid.2023.08.001. Epub 2023 Aug 10.

Authors

Liang Fu¹, Xilin Zhang², Juan Xiong³, Feng Sun⁴, Taoping Weng⁴, Yang Li⁴, Peize Zhang¹, Hui Li¹, Qianting Yang⁵, Yi Cai⁶, Hancheng Liang⁷, Qiuqi Chen⁸, Zhaoqing Wang¹, Lei Liu¹, Xinchun Chen⁶, Wenhong Zhang⁴, Guofang Deng⁹

Affiliations

¹ Division Two of Pulmonary Diseases Department, National Clinical Research Center for Infectious Disease (Shenzhen), Guangdong Provincial Clinical Research Center for Infectious Diseases (Tuberculosis), Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China.
² Tuberculosis Prevention and Control Department, The Fourth People's Hospital of Foshan, Foshan, China.
³ Health Science Center, Shenzhen University, Shenzhen, China.
⁴ Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
⁵ Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Disease, Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, China.
⁶ Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, China.
⁷ Division Two of Tuberculosis Diseases Department, The Sixth People's Hospital of Dongguan, Dongguan, China.
⁸ Graduate School of Guangdong Medical University, Zhanjiang, China.
⁹ Division Two of Pulmonary Diseases Department, National Clinical Research Center for Infectious Disease (Shenzhen), Guangdong Provincial Clinical Research Center for Infectious Diseases (Tuberculosis), Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China. Electronic address: jxxk1035@yeah.net.

PMID: 37567554
DOI: 10.1016/j.ijid.2023.08.001

Abstract

Objectives: Long, ineffective, and toxic regimens hinder the treatment of patients with multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant tuberculosis (pre-XDR-TB).

Methods: We conducted a multicenter cohort study to prospectively evaluate the safety and efficacy of three 9-month, all-oral, 5-drug regimens. Regimen A (bedaquiline [Bdq]+linezolid [Lzd]+moxifloxacin [Mfx]+cycloserine [Cs]+pyrazinamide [Pza]) and Regimen B (Lzd+Mfx+Cs+clofazimine [Cfz]+Pza) were used to treat MDR-TB patients (Groups A and B, respectively, assigned according to the patient's treatment preference), while Regimen C (Bdq+Lzd+Cs+Cfz+Pza) was used to treat pre-XDR-TB patients (Group C). The primary endpoint was the occurrence of an unfavorable outcome within 12 months of treatment completion, regardless of regimen.

Results: A total of 104 patients (34 in Group A, 46 in Group B, and 24 in Group C), with a median age of 35.5 (29.0-54.0) years, were included in the analysis population. At 12 months after treatment completion, five patients were deemed non-assessable. Of the remaining 99 participants, seven (7.1%) had an unfavorable outcome (including two deaths from any cause, four with treatment failure, and one loss to follow-up) and 92 (92.9%) had a favorable outcome. Culture conversion was achieved in 82.5% (80/97) of participants at month 2 and in 97.9% (94/97) of participants at month 6. Adverse events (AEs) resulting in drug adjustment occurred in 69.2% (72/104) of participants, mainly due to Lzd and Pza use. A QT interval prolongation of ≥ 500 ms occurred in 5.8% (6/104) of participants.

Conclusion: The primary outcome of the three tailored, 9-month, all-oral, 5-drug regimens was satisfactory in the vast majority of MDR-TB and pre-XDR-TB patients, with manageable and reversible AEs.

Keywords: Multidrug-resistant tuberculosis; Pre-extensive drug-resistant tuberculosis; Safety; Short-course; Treatment.