Long-term results of chemotherapy of tuberculosis with a widespread drug-resistant pathogen using bedaquiline

Relevance. Long-term results of treatment of patients with widespread drug-resistant tuberculosis are not presented in the medical literature. Objective. Study the efficacy and long-term results of treatment of patients with widespread drug-resistant tuberculosis using bedaquiline. Material and methods. Two groups of patients with widespread drug-resistant tuberculosis were formed, who received bedaquiline as the base drug of the chemotherapy course: bedaquiline in the main group (49 people) and moxifloxacin in the control group (76 people). The results of treatment at the end of the course of chemotherapy and after three years of follow-up were studied. Results. 87.8±9.2% of patients from the main group completed an effective course of treatment with sputum culture control. In 67.3±13.1%, the cessation of bacillus excretion was achieved at 1–2 months of treatment. Undesirable effects of chemotherapy were noted in 10.2–32.7% of cases, with prolongation of the QT interval only in 8.2±7.7% of patients. After a three-year dispensary follow-up, there was no recurrence of tuberculosis in the main group, chronic obstructive pulmonary disease was less common for the fifirst time, no cases of treatment by a cardiologist and gynecologist were found, the transfer of patients from the second disability group to the third was more often observed. Conclusion. The use of bedaquiline for the treatment of patients with widespread drug-resistant tuberculosis makes it possible to achieve early cessation of bacillus excretion with transfer to outpatient treatment, reduce the frequency of adverse reactions of chemotherapy. The long-term results of dispensary observation indicate a low risk of reactivation of tuberculosis, a significant reduction in the need for dispensary observation by other specialists, including a cardiologist, and improvement in the results of complex rehabilitation.

1. Ministerstvo zdravoohraneniya Rossijskoj Federacii, Rossijskoe obshchestvo ftiziatrov, Associaciya ftiziatrov. Klinicheskie rekomendacii Tuberkulyoz u vzroslyh. Moscow: 2022; 151. Dostupno po ssylke: https://cr.minzdrav.gov.ru/ schema/16_2. (in Russian)

2. Global tuberculosis report 2017. Geneva, World Health Organization; 2017; 262.

3. Schnippel K., Firnhaber C., Page-Shipp L., Sinanovic E. Impact of adverse drug reactions on the incremental cost-effectiveness of bedaquiline for drug-resistant tuberculosis. Int J Tuberc Lung Dis. 2018; 22 (8): 918–925. doi:10.5588/ijtld.17.0869.

4. Sarathy J.P., Gruber G., Dick T. Re-Understanding the Mechanisms of Action of the Anti-Mycobacterial Drug Bedaquiline. Antibiotics (Basel). 2019; 8 (4): 261. doi: 10.3390/antibiotics8040261.

5. Konovalova M.N., Odinec V.S., Vasilenko T.I., Zadremajlova T.A. Opyt primeneniya preparata bedakvilin v lechenii bol'nyh tuberkulyozom lyogkih s mnozhestvennoj i shirokoj lekarstvennoj ustojchivost'yu vozbuditelya. Tuberkulyoz i Bolezni Lyogkih. 2017; 95 (12): 49–53. doi: https://doi.org/10.21292/2075-1230-2017-95-12-49-53.

6. Fan Q., Ming W.K., Yip W.Y., You J.H.S. Cost-effectiveness of bedaquiline or delamanid plus background regimen for multidrug-resistant tuberculosis in a high-income intermediate burden city of China. Int J Infect Dis. 2019; 78: 44–49. doi: 10.1016/j.ijid.2018.10.007.

7. Borisov S.E., Dheda K., Enwerem M., Leyet R.R., D`Ambrosio L., Centis R. et al. Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study. Eur Respir J. 2017; 49 (5): 1700387. doi: 10.1183/13993003.00387-2017.

8. Gao M., Gao J., Xie L., Wu G., Chen W., Chen Y. et al. Early outcome and safety of bedaquiline-containing regimens for treatment of MDR- and XDR-TB in China: a multicentre study. Clin Microbiol Infect. 2021; 27 (4): 597–602. doi: 10.1016/j.cmi.2020.06.004.

9. Yao C., Guo H., Li Q., Zhang X., Shang Y., Li T. et al. Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition. Antimicrob Resist Infect Control. 2021; 10 (1): 126. doi: 10.1186/s13756-021-00995-8.

10. Mbuagbaw L., Guglielmetti L., Hewison C., Bakare N., Bastard M., Caumes E. et al. Outcomes of bedaquiline treatment in patients with multidrugresistant tuberculosis. Emerg Infect Dis. 2019; 25 (5): 936–943. doi: 10.3201/eid2505.181823.

11. Rahul H.P., Pawara R., Pawara K., Ahmed F., Shirkhedkar A., Suraha S. A structural insight of bedaquiline for the cardiotoxicity and hepatotoxicity. Tuberculossis. 2019; 117: 79–84. doi:10.1016/j.tube.2019.06.005.

12. Fox G.J., Menzies D. A review of the evidence for using bedaquiline (TMC207) to treat multi-drug resistant tuberculosis. Infect. Dis. Ther. 2013; 2 (2): 123–144. doi: 10.1007/s40121-013-0009-3.

13. Mozhokina G.N., Samojlova A.G. Kardiotoksicheskie svojstva ftorhinolonov i bedakvilina. Tuberkulez i Bolezni Legkih. 2019; 97 (4): 56–62. doi: https://doi.org/10.21292/2075-1230-2019-97-4-56-62. (in Russian)

14. Parpieva N.N., Abulkasimov S.P., Pulatov Zh.A., Muhtorov Sh.N., Ajtzhanova A.U. Pobochnye nezhelatel'nye yavleniya pri primenenii bedakvilina v rezhime lecheniya bol'nyh s SHLU TB. Molodoj uchenyj. 2018; 10 (1): 31–33. (in Russian)

15. Mozhokina G.N., Samojlova A.G., Zangieva Z.A. Nefrotoksicheskie svojstva protivotuberkuleznyh preparatov. Tuberkulez i Bolezni Legkih. 2019; 97 (10): 59–65. doi: https://doi.org/10.21292/2075-1230-2019-97-10-59-65. (in Russian)

16. Tihonova L.YU., Sokolova V.V., Tarasyuk I.A., Ekimenko A.M. Opyt primeneniya preparata bedakvilin u bol'nyh tuberkulezom s mnozhestvennoj lekarstvennoj ustojchivost'yu vozbuditelya v Amurskoj oblasti. Tuberkulez i Bolezni Legkih. 2018; 96 (6): 45–50. doi: https://doi.org/10.21292/2075-1230-2018-96-6-45-50. (in Russian).

17. Rhee C.K., Yoo K.H., Lee J.H. et al. Clinical characteristics of patients with tuberculosis-destroyed lung. Int J Tuberc Lung Dis. 2013; 17 (1): 67–75. doi: 10.5588/ijtld.12.0351.

18. Allwood B.W., Byrne A., Meghji J., Rachow A., van der Zalm M.M., Schoch O.D. Post-tuberculosis lung disease: clinical review of an under-recognised global. Respiration. 2021; 100 (8): 751–763. doi: 10.1159/000512531.

19. Sarkar M., Srinivasa А., Madabhavi I., Kumar L.K. Tuberculosis associated chronic obstructive pulmonary disease. Clin Resp J. 2017; 11 (3): 285–295. doi: 10.1111/crj.12621.

20. Khoshnood S., Goudarzi M., Taki E., Darbandi A., Kouhsari E., Heidary M. Bedaquiline: Current status and future perspectives. J Glob Antimicrob Resist. 2021 June; 25: 48–59. doi:10.1016/j.jgar.2021.02.017.

21. Lewis J.M., Hine P.,Walker J. et al. First experience of effectiveness and safety of bedaquiline for 18 months within an optimised regimen for XDR-TB. Eur Respir J. 2016; 47: 1581–1584. doi: 10.1183/13993003.01980-2015.

22. Caminero J.A., Piubello A., Scardigli A. et al. Proposal for a standardised treatment regimen to manage pre- and extensively drug-resistant tuberculosis cases. Eur Respir J. 2017; 50: 1700648. doi: 10.1183/13993003.00648-2017.

23. Furin J., Lessem E., Cox V. Recommending prolonged bedaquiline use for the treatment of highly resistant strains of tuberculosis. Eur Respir J. 2017; 50 (5): 1701552. doi: 10.1183/13993003.01552-2017.

24. Svensson E.M., Karlsson M.O. Modelling of mycobacterial load reveals bedaquiline’s exposure-response relationship in patients with drug-resistant TB. J Antimicrob Chemother. 2017; 72 (12): 3398–3405. doi: 10.1093/jac/dkx317.

25. Salinger D.H., Nedelman J.R., Mendel C., Spigelman M., Hermann D.J. Daily dosing for bedaquiline in patients with tuberculosis. Antimicrob Agents Chemother. 2019; 63 (11): 463–419. doi: 10.1128/AAC.00463-19.