Features of the pathogen and efficacy of drug-resistant tuberculosis treatment

According to the World Health Organization (WHO), nearly 10.6 million new cases of tuberculosis were detected in 2022, indicating an increase of 3.5 % from the reported 10.3 million in 2021. After the COVID-19 pandemic, the incidence of tuberculosis increased by 3.9 % from 2020 to 2022. According to the latest regulatory documents, multidrug-resistant pathogen is diagnosed when any bacteriologic or molecular genetic methods reveal drug resistance of M. Tuberculosis complex at least to isoniazid and rifampicin regardless of resistance to other antituberculosis drugs.

With a wide range of virulence genes, the tuberculosis pathogen expresses genes in different phases of infection. Some genes are “switched on” in the early phases and are important for overcoming immune defenses and spreading the pathogen in the host, while others are important for survival in the latent phase. These characteristics of Mycobacterium tuberculosis determine the need for correct and adequate selection of therapy. The problem of diagnostics and treatment of drug-resistant tuberculosis remains extremely urgent. Despite the introduction of new tests for rapid determination of drug susceptibility spectrum of Mycobacterium tuberculosis, the problem of timely and adequate prescription of chemotherapy regimen remains. When selecting therapy, the problem of prescribing a combination of antituberculosis drugs with proven efficacy against M. tuberculosis remains. The need to assess the patient’s comorbid status, which affects the effectiveness of treatment and the occurrence of relapses, remains relevant.

Despite the introduction of new tests for rapid determination of the drug susceptibility spectrum of Mycobacterium tuberculosis, the problem of timely and adequate prescription of chemotherapy remains relevant. The problem of prescribing a combination of antituberculosis drugs with proven efficacy against M. tuberculosis remains in the selection of therapy. Currently, the introduction of bedaquiline in therapy regimens is important for improving the effectiveness of tuberculosis treatment. In addition, studies are underway to shorten the duration of therapy for MDR-TB and XDR-TB, which is particularly important for maintaining patient adherence to treatment.

1. WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-susceptible tuberculosis treatment. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO.

2. Mitnick C, Khan U, Guglielmetti L, et al. SP01 Innovation to guide practice in MDR/RR-TB treatment: efficacy and safety results of the end TB trial. Presented at: Union World Conference on Lung Health. 2023 November 15. https://theunion.floq.live/event/worldconf2023/symposia?objectClass=timeslot&objectId=64ef5819e-0400915b209e22f&type=detail.

3. Global tuberculosis report 2023. Geneva: World Health Organization; 2023. Licence: CC BY-NC- SA 3.0 IGO, ISBN 978-92-4-008385-1.

4. Starshinova AA, Vishnevski BI, Grashenkov AS et al. Principles of differential diagnosis of tuberculosis of the respiratory system and other lung diseases. In Russian

5. Sabin S, Herbig A, Vågene ÅJ, et al. A seventeenth-century Mycobacterium tuberculosis genome supports a Neolithic emergence of the Mycobacterium tuberculosis complex. Genome Biol. 2020; 21, 201. DOI: 10.1186/s13059-020-02112-1.

6. Masson M, Bereczki Z, Molnár E, et al. 7000 yearold tuberculosis cases from Hungary — Osteological and Biomolecular Evidence, Tuberculosis. 2015; 1:S13–7. DOI: 10.1016/j.tube.2015.02.007.

7. Gupta RS, Lo B, Son J. Phylogenomics and Comparative Genomic Studies Robustly Support Division of the Genus Mycobacterium nto an Emended Genus Mycobacterium and Four Novel Genera. Front. Microbiol. 2018; 13: 9:67. DOI: 10.3389/fmicb.2018.00067.

8. Wanger A, Chavez V, Huang RSP, et al. Mycobacterium tuberculosis complex comprises M. tuberculosis, M. bovis, M. bovis BCG, Mycobacterium africanum, among others. Microbiology and Molecular Diagnosis in Pathology. 2017; 75–117. DOI: 10.1016/B978-0-12-805351-5.00006-5.

9. Damene H, Tahir D, Diels M, et al. Broad diversity of Mycobacterium tuberculosis complex strains isolated from humans and cattle in Northern Algeria suggests a zoonotic transmission cycle. PLoS Negl Trop Dis. 2020; 30:14:11: e0008894. DOI: 10.1371/journal.pntd.0008894.

10. Godreuil S, Torrea G, Terru D, et al. First Molecular Epidemiology Study of Mycobacterium tuberculosis in Burkina Faso. J Clin Microbiol. 2007; 45:3: 921–927. DOI: 10.1128/JCM.01918-06.

11. Mokrousov I, Chernyaeva E, Vyazovaya A, et al. Rapid Assay for Detection of the Epidemiologically Important Central Asian/Russian Strain of the Mycobacterium tuberculosis Beijing Genotype. J Clin Microbiol. 2018; 56:2: e01551–17. DOI: 10.1128/JCM.01551-17.

12. Vyazovaya A, Gerasimova A, Mudarisova R, et al. Genetic Diversity and Primary Drug Resistance of Mycobacterium tuberculosis Beijing Genotype Strains in North-western Russia. Microorganisms. 2023; 11:2: 255. DOI: 10.3390/microorganisms11020255.

13. Krajewski WW, Jones TA, Mowbray SL. Structure of Mycobacterium tuberculosis glutamine synthetase in complex with a transition-state mimic provides functional insights. PNAS, 2005; 102:30: 10499–10504. DOI: 10.1073/pnas.0502248102.

14. Massino SV. Main stages of development of tuberculosis in the USSR. The Tuberculosis Handbook edited by A. I. Lapinа and S. V. Massino. Moscow: Medgiz. 1962; 4: 9–24. In Russian

15. Starshinova AA, Pavlova MV, Yablonskiy PK, et al. Evolution of phthisiatry — a search for new methods and drugs effective for the treatment of tuberculosis. Prakticheskaya medicina=Practical medicine. 2014; 7:83: 127–132. In Russian

16. Tuberculosis in the Russian Federation 2011 Analytical Review of Statistical Indicators Used in the Russian Federation and in the World. 2015; Moscow. 280 p.

17. Borisov SE, Filippov AV, Ivanova DA, et al. Efficacy and safety of chemotherapy regimens with bedaquiline in patients with respiratory tuberculosis: immediate and final results. Tuberculosis and Lung Diseases. 2019;97(5):28–42. (In Russ.) DOI: 10.21292/2075-1230-2019-97-5-28-40.

18. WHO consolidated guidelines on tuberculosis: Module 3: diagnosis – rapid diagnostics for tuberculosis detection [Internet] 732. https://pubmed.ncbi.nlm.nih.gov/33999549/ (accessed on Aug 28, 2023)

19. WHO. The Use of Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis: Interim Policy Guidance; WHO: Geneva, Switzerland, 2013; 57p.

20. Kudlay DA. Development and introduction into clinical practice of a new pharmacological substance from the class of diarylquinolines. Exp. Clin. Pharmacol. 2021; 84: 41–47. In Russian DOI: 10.30906/0869-2092-2021-84-3-41-47.

21. Mitnick C, Khan U, Guglielmetti L, et al. SP01 Innovation to guide practice in MDR/RR-TB treatment: efficacy and safety results of the end TB trial. Presented at: Union World Conference on Lung Health. 2023 November 15. https://theunion.floq.live/event/worldconf2023/symposia?objectClass=timeslot&objectId=64ef5819e-0400915b209e22f&type=detail.

22. WHO consolidated guidelines on tuberculosis. Module 5: management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022.

23. Borisov SE, Dheda K, Enwerem M, 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.

24. Starshinova AA, Dovgalyuk IF, Osipov NN, et al. Bedaquiline Efficacy in the Russian Federation: Meta-Analysis with a Random Effects Model. Tuberkulez i bolezni legkix=Tuberculosis and Lung Diseases. 2023; 101:3: 52–61. In Russian DOI: 10.58838/2075-1230-2023-101-3-52-61.

25. Yablonsky PK, Starshinova AA, Nazarenko MM, et al. Efficiency of new chemotherapy regimens in patients with extensive drug resistance of the pathogen. Bull. Mod. Clin. Med. 2022; 15: 67–75. DOI: 10.20969/VSKM.2022.15(2).

26. Stavitskaya NV, Felker IG, Zhukova EM, et al. The multivariate analysis of results of bedaquiline use in the therapy of MDR/XDR pulmonary tuberculosis. Tuberkulez i bolezni legkix=Tuberculosis and Lung Diseases, 2020; 98:7: 56–62. In Russian DOI: 10.21292/2075-1230-2020-98-7-56-62.