Feng Ding,1,2 Sinian Li,2,3 Xiangxiang Liu,1,2 Guoju Shao,2,3 Youfeng Su,2,3 Yan Qian,1,2 Zhi Mao,2,3 Jianfeng Zeng,2,3 Shuihua Lu,1– 3 Mutong Fang2,3 

1National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2The Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Pulmonary Diseases, Shenzhen Third People’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China

Correspondence: Mutong Fang, Department of Pulmonary Diseases, Shenzhen Third People’s Hospital, No. 29, Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel +86 755 61222333, Fax +86 755 61238928, Email 1049179464@qq.com Shuihua Lu, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, No. 29, Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel +86 755 61222333, Fax +86 755 61238928, Email lushuihua66@126.com

Purpose: The objective of this study was to evaluate the efficacy of bedaquiline (Bdq)-containing regimens in pre-extensively drug-resistant tuberculosis (pre-XDR-TB) patients in Shenzhen, China, and to investigate the association between Bdq resistance and unfavorable outcomes.
Methods: Data were collected from 84 pre-XDR-TB patients categorized into Bdq (n = 46) and non-Bdq (n = 38) groups. Individuals in the Bdq group were treated with Bdq alongside individualized background drugs. Commonly used drugs (> 50% of patients) in both groups were linezolid (Lzd), clofazimine (Cfz), cycloserine (Cs) and pyrazinamide (Pza). Treatment outcomes were classified as cure, treatment completion, treatment failure, loss to follow-up, or death. Logistic regression analysis was conducted to determine independent predictors of treatment success using potential risk factors, including age, sex, body mass index (BMI), TB treatment history, and other factors. Whole-genome sequencing (WGS) was conducted on clinical isolates from 4 patients with unfavorable outcomes and 4 patients with favorable outcomes in the Bdq group.
Results: Favorable treatment outcomes were observed in 89.13% (41/46) of the Bdq group and 52.63% (20/38) of the non-Bdq group (P = 0.0005). Univariate and multivariate analyses identified Bdq was an independent factor associated with treatment success (odds ratio [OR] = 11.572, 95% CI: 2.183– 61.343, P = 0.004). WGS identified an atpE_Ala63Pro mutation conferring Bdq resistance in one patient with an unfavorable outcome. Additional resistance mutations included Rv0678_Arg156fs (Bdq and Cfz resistance) and rplC_Cys154Arg (Lzd resistance).
Conclusion: Bdq-containing regimens significantly improved the treatment outcomes among pre-XDR-TB patients. The emergence of resistance mutations highlights the importance of routine drug resistance monitoring and rational drug use. Expanding access to Bdq and other novel drugs at affordable prices is vital for improving the success of pre-XDR-TB treatment.

Keywords: Bdq-containing regimen, pre-XDR-TB, treatment outcomes, resistance, WGS