Effectiveness of chemotherapy of multidrug-resistant tuberculosis using bedaquiline

The aim of the study was to evaluate the effectiveness of MDR/XDR TB treatment with bedaquiline. 
Methods. The author analyzed the treatment results of 56 patients in Staint Petersburg in 2017 with MDR/XDR TB whose treatment regimen included bedaquiline. All patients were smear/ culture-positive: 43 (67.8%) cases with XDR MBT; 7 (12.5%) with pre-XDR MBT and only 6 (10.7 %) cases with MDR TB. 
Results. 35 (62.5%) patients received full bedaquiline course, 16 received the treatment for a few days to 4 months and did not complete the course, 5 patients with XDR tuberculosis who underwent surgery were treated for more than 6 months. The average duration of bedaquiline course was 4.7 ± 0.3 months. Among the 27 (48.2%) patients who completed the treatment effectively, 22 had XDR TB, 3 – pre-XDR TB, and 2 – MDR TB. The median sputum conversion period was 4.00 ± 0.42 months (CI: 3.14 – 4.86). 13 (23.2%) patients interrupted the treatment, but 9 of them had negative cultures for MBT at this time. These patients received bedaquiline for 1 to 14 months. Treatment failure was recorded in 12 (21.4%) patients, and 4 (7.14%) patients died during the intensive treatment phase. In general, 27 patients with a successful outcome had negative cultures at the end of the intensive phase and 9 patients who effectively completed the intensive phase but interrupted the treatment continuation phase. In total, 36 patients (64.3%) had a successful treatment outcome. 
Conclusion. The analysis showed that routine administration of the drug without consideration for treatment compliance increases the effectiveness of the intensive phase (64.3%) and does not significantly affect general effectiveness of the treatment (48.2%). The high frequency of treatment interruption remains a serious obstacle to improving the treatment effectiveness.

1. Vasil’eva I.A., Belilovskij E.M., Borisov S.E., Sterlikov S.A. [Multi drug resistant tuberculosis in the world and Russian Federation]. Tuberkulez i bolezni legkih. 2017, 95 (11): 5–17. DOI: 10.21292/2075-1230-2017-95-11-5-17 (in Russian).

2. Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization; 2011. Available at: https://apps.who.int/iris/bitstream/handle/10665/44597/9789241501583_eng.pdf;jsessionid=15B51F3D928C3A3877156D07956EE7A0?sequence=1

3. Matteelli A., D’Ambrosio L., Centis R. et al. Compassionate and optimum use of new tuberculosis drugs. Lancet Infect. Dis. 2015; 15 (10): 1131–1132. DOI: 10.1016/S1473-3099(15)00296-0.

4. Trauer J.M. TB, you’re a long time cured. Eur. Respir. J. 2019; 53 (3): 1900104. DOI: 10.1183/13993003.00104-2019.

5. Ivanova D.A., Borisov S.E., Rodina O.V. et al. [Safety of treatment regimens in multiple drug resistant tuberculosis patients compiled as per the new WHO recommendations as of 2019]. Tuberkulez i bolezni legkikh. 2020; 98 (1): 5–15. DOI: 10.21292/2075-1230-2020-98-1-5-15 (in Russian).

6. WHO consolidated guidelines on drug-resistant tuberculosis treatment. WHO/CDS/TB/2019.3. Geneva: World Health Organization; 2019. Available at: https://apps.who.int/iris/bitstream/handle/10665/311389/9789241550529-eng.pdf?sequence=1&isAllowed=y

7. The use of bedaquiline in the treatment of multidrug-resistant tuberculosis: interim policy guidance. Geneva: World Health Organization; 2013. Available at: https://www.ncbi.nlm.nih.gov/books/NBK154134/

8. Gandhi N.R., Brust J.C.M., Shah N.S. A new era for treatment of drug-resistant tuberculosis. Eur. Respir. J. 2018; 52 (4): 1801350 DOI: 10.1183/13993003.01350-2018.

9. Report of the Guideline Development Group Meeting on the use of bedaquiline in the treatment of multidrug-resistant tuberculosis: a review of available evidence (2016). Geneva: World Health Organization; 2017. Available at: https://apps.who.int/iris/bitstream/handle/10665/254712/WHO-HTM-TB-2017.01-eng.pdf?sequence=1&isAllowed=y

10. Pontali E., Raviglione M.C., Migliori G.B. et al. Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives. Eur. Respir. Rev. 2019; 28 (152): 190035. DOI: 10.1183/16000617.0035-2019.

11. Dheda K., Chang K.C., Guglielmetti L. et al. Clinical management of adults and children with multidrug-resistant and extensively drug-resistant tuberculosis. Clin. Microbiol. Infect. 2017; 23 (3): 131–140. DOI: 10.1016/j.cmi.2016.10.008.

12. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization; 2014. Available at: https://apps.who.int/iris/bitstream/handle/10665/130918/9789241548809_eng.pdf

13. WHO treatment guidelines for drug-resistant tuberculosis. 2016 update. Geneva: World Health Organization; 2016. Available at: https://apps.who.int/iris/bitstream/handle/10665/250125/9789241549639-eng.pdf

14. Definitions and reporting framework for tuberculosis – 2013 revision (updated December 2014 and January 2020). Geneva: World Health Organization 2013. Available at: https://apps.who.int/iris/bitstream/handle/10665/79199/9789241505345_eng.pdf

15. Global Tuberculosis Report. Geneva: World Health Organization; 2018. Available at: https://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf?sequence=1&isAllowed=y

16. Harari S. Randomised controlled trials and real-life studies: two answers for one question. Eur. Respir. Rev. 2018; 27 (149): 180080. DOI: 10.1183/16000617.0080-2018.

17. Diacon A.H., Pym. A., Grobusch M.P. et al. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N. Engl. J. Med. 2014, 371 (8): 723–732. DOI: 10.1056/NEJMoa1313865.

18. Olayanju O., Limberis J., Esmail A. et al. Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa. Eur. Respir. J. 2018; 51 (5): 1800544. DOI: 10.1183/13993003.00544-2018.

19. Mbuagbaw L., Guglielmetti L., Hewison C. et al. Outcomes of bedaquiline treatment in patients with multidrug-resistant tuberculosis. Emerg. Infect. Dis. 2019, 25 (5): 936–943. DOI: 10.3201/eid2505.181823.

20. Ministry of Health of the Russian Federation. [Tuberculosis in adults: Clinical guidelines]. 2020. Available at: https://cr.minzdrav.gov.ru/schema/16_1 (in Russian).