M Gao1, J Gao2, L Xie1, G Wu3, W Chen4, Y Chen5, Y Pei6, G Li7, Y Liu2, W Shu2, L Fan8, Q Wu9, J Du10, X Chen11, P Tang12, Y Xiong13, M Li14, Q Cai15, L Jin16, Z Mei17, Y Pang18, L Li19. 1. Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing, PR China. 2. Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, PR China. 3. Department of Tuberculosis, Chengdu Public Health Clinical Centre, Chengdu, PR China. 4. Department of Tuberculosis, Shenyang Chest Hospital, Shenyang, PR China. 5. Department of Tuberculosis, Henan Provincial Infectious Disease Hospital, Zhengzhou, PR China. 6. Department of Tuberculosis, Changsha Central Hospital, Changsha, PR China. 7. Department of Tuberculosis, The Third People's Hospital of Shenzhen, Shenzhen, PR China. 8. Department of Tuberculosis, Shanghai Pulmonary Hospital, Shanghai, PR China. 9. Department of Tuberculosis, Shaanxi Provincial Tuberculosis Institute, Xi'an, PR China. 10. Department of Tuberculosis, Wuhan Pulmonary Hospital, Wuhan, PR China. 11. Department of Tuberculosis, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, PR China. 12. Department of Tuberculosis, The Fifth People's Hospital of Suzhou, Infectious Disease Hospital Affiliated to Soochow University, Suzhou, PR China. 13. Department of Tuberculosis, Shandong Provincial Chest Hospital, Jinan, PR China. 14. Department of Tuberculosis, Kunming Third People's Hospital, Kunming, PR China. 15. Department of Tuberculosis, Hangzhou Red Cross Hospital, Hangzhou, PR China. 16. Department of Tuberculosis, Infectious Diseases Hospital Heilongjiang Province, Harbin, PR China. 17. Department of Tuberculosis, Tianjin Haihe Hospital, Tianjin, PR China. 18. Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, PR China; National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, PR China. Electronic address: pangyupound@163.com. 19. Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, PR China. Electronic address: liliang69@tb123.org.
Abstract
OBJECTIVES: Bedaquiline treatment significantly improves multidrug-resistant tuberculosis (MDR-TB) patient treatment outcomes. However, safety and efficacy data are lacking for bedaquiline used with background regimens to treat Chinese TB patients. Here, we describe our initial clinical experience for bedaquiline treatment of a large multicentre cohort of MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patients in China. METHODS: Patients (177) received 24-week bedaquiline treatment combined with personalized anti-TB drug background regimens. As primary efficacy endpoints, times to initial sputum culture conversion were measured. RESULTS: Of 177 MDR-TB patients completing the 24-week treatment course, sputum culture conversion occurred for 151/177 (85.3%), while 26 had unfavourable outcomes, including 3/177 (1.7%) deaths and 23/177 (13.0%) non-responders at treatment completion. The median time to sputum culture conversion was 4 (interquartile range 2-8) weeks. Conversion rates were 33/39 (84.6%, 95% confidence interval (CI) 73.3-95.9) for MDR-TB patients, 47/56 (83.9%, 95% CI 74.3-93.6) for pre-XDR-TB patients and 71/82 (86.6%, 95% CI 79.2-94.0) for XDR-TB patients. Multivariate analysis demonstrated that patients with low body mass index (odds ratio 7.356; 95% CI 2.652-20.401) were at significantly high risk of unfavourable outcomes, with serious adverse events noted in 15 (8.5%) patients, including six with corrected QT interval (QTc) prolongation times (>500 ms). CONCLUSION: Bedaquiline, when included in background regimens for treatment of MDR-TB and XDR-TB patients in China, was safe and associated with a high rate of culture conversion.
OBJECTIVES:Bedaquiline treatment significantly improves multidrug-resistant tuberculosis (MDR-TB) patient treatment outcomes. However, safety and efficacy data are lacking for bedaquiline used with background regimens to treat Chinese TB patients. Here, we describe our initial clinical experience for bedaquiline treatment of a large multicentre cohort of MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patients in China. METHODS:Patients (177) received 24-week bedaquiline treatment combined with personalized anti-TB drug background regimens. As primary efficacy endpoints, times to initial sputum culture conversion were measured. RESULTS: Of 177 MDR-TB patients completing the 24-week treatment course, sputum culture conversion occurred for 151/177 (85.3%), while 26 had unfavourable outcomes, including 3/177 (1.7%) deaths and 23/177 (13.0%) non-responders at treatment completion. The median time to sputum culture conversion was 4 (interquartile range 2-8) weeks. Conversion rates were 33/39 (84.6%, 95% confidence interval (CI) 73.3-95.9) for MDR-TB patients, 47/56 (83.9%, 95% CI 74.3-93.6) for pre-XDR-TB patients and 71/82 (86.6%, 95% CI 79.2-94.0) for XDR-TB patients. Multivariate analysis demonstrated that patients with low body mass index (odds ratio 7.356; 95% CI 2.652-20.401) were at significantly high risk of unfavourable outcomes, with serious adverse events noted in 15 (8.5%) patients, including six with corrected QT interval (QTc) prolongation times (>500 ms). CONCLUSION:Bedaquiline, when included in background regimens for treatment of MDR-TB and XDR-TB patients in China, was safe and associated with a high rate of culture conversion.