Detection of Mycobacterium tuberculosis resistance to bedaquiline, delamanid, linezolid, and fluoroquinolones in the practice of a centralized bacteriological laboratory in Moscow

Due to the widespread circulation of multi drug resistant (MDR) M. tuberculosis (MTB) strains it’s very important to determine MTB strains susceptibility to relatively new anti-TB drugs and repurposed antibacterial agents formed the basis of chemotherapy regimens and MTB resistance to them is a hallmark of pre-XDR and XDR.

The aim. Analysis of the results of culture-based drug susceptibility testing of clinical MDR MTB strains for bedaquiline, delamanid, linezolid, levofloxacin, and moxifloxacin in a centralized bacteriological laboratory and assessment the frequency of detection of pathogens with preand extreme drug resistance.

Materials and Methods. Our retrospective study included 171 clinical MDR MTB isolates from 171 patients with active TB. Drug susceptibility testing was performed with the help of a modified proportion method in the BactecTMMGITTM 960 automated system.

Results. The proportion of resistant strains to levofloxacin and moxifloxacin was 36.8% and 38.0%, respectively, the pathogen showed high cross-resistance (97%) to these drugs. The proportion of strains resistant to bedaquiline, delamanid, and linezolid was low: 1.2%, 4.7%, and 3.5%, respectively. 33.9% of strains were pre-XDR and 4.1% of all multidrug-resistant (MDR) strains were XDR. Conclusion. We determined high levels of resistance to fluoroquinolones, while bedaquiline delamanid, and linezolid retain high activity against MDR MTB strains. Systematic monitoring of resistance to anti-TB drugs of circulating MTB strains’ is essential for the timely detection and prevention of their potential speading.

1. Белиловский Е.М., Михайлова Ю.Д., Темлякова А.О. и др. Результаты пилотного исследования распространения туберкулеза с лекарственной устойчивостью возбудителя в городе Москве // Туберкулез и социально значимые заболевания. − 2019. − № 3. − С. 4−12.

2. Васильева И.А., Тестов В.В., Стерликов С.А. и др. Сравнительный анализ результатов тестирования лекарственной чувствительности M. tuberculosis среди случаев туберкулеза в России в 2023–2024 гг. // Туберкулез и болезни легких. – 2025. –Т. 103. − №5. – С. 8−14.

3. Клинические рекомендации «Туберкулез у взрослых» / Утв. Минздравом России. – 2026. [Электронный ресурс] https://medaccreditation.online/klinicheskiye_rekomendatsii/tuberkulez-u-vzroslyh_16_4_4

4. Литвинов В.И., Сельцовский П.П., Рыбка Л.Н. и др. Эпидемиологическая ситуация по туберкулезу и организация противотуберкулезной помощи населению Москвы (2008 г.). – М.: МНПЦБТ, 2009. – 149 c.

5. Михайлова Ю.Д., Макарова М.В., Крылова Л.Ю. и др. Изучение чувствительности Mycobacterium tuberculosis к деламаниду с использованием автоматизированной системы BACTECTM MGITTM 960 // Туберкулез и социально значимые заболевания. − 2024. –Т.12. – №12. − С. 25−35.

6. Михайлова Ю.Д., Макарова М.В., Кудлай Д.А. и др. Количественная оценка чувствительности Mycobacterium tuberculosis к линезолиду // Туберкулез и социально значимые заболевания. − 2019. − № 1. − С. 19−24.

7. Перетокина И.В., Крылова Л.Ю., Сафонова С.Г. и др. Определение пограничного значения минимальной ингибирующей концентрации бедаквилина в отношении чувствительных клинических штаммов Mycobacterium tuberculosis на разных питательных средах // Туберкулез и социально значимые заболевания. − 2018. − № 3. − С. 32−35.

8. Эпидемиология, профилактика и лечение туберкулеза в г. Москве, 2023 г. / Под ред. Е.М. Богородской, В.И. Литвинова, Е.М. Белиловского. − Воронеж: ООО «Славяночка», 2025. − 336 с.

9. DevasiaR.A., BlackmanA., MayC. etal. FluoroquinoloneresistanceinMycobacteriumtuberculosis: anassessmentofMGIT 960, MODS and nitrate reductase assay and fluoroquinolone cross-resistance // J. Antimicrob. Chemother. − 2009. − Vol. 63, № 6. − P. 1173-1178. doi: 10.1093/jac/dkp096

10. He W., Liu C., Liu D. et al. Prevalence of Mycobacterium tuberculosis resistant to bedaquiline and delamanid in China // J. Glob. Antimicrob. Resist. − 2021. − Vol. 26. − P. 241−248. doi: 10.1016/j.jgar.2021.06.007

11. Kalalahti I., Huotari K., Lahdensuo K.et al. Rectal E. coli above ciprofloxacin ECOFF associate with infectious complications following prostate biopsy // Eur. J. Clin. Microbiol. Infect. Dis. − 2018. − Vol. 37, № 6.− P. 1055−1060. doi: 10.1007/s10096-018-3217-7

12. Mamatha H.G., ShanthiV. Baseline resistance and cross-resistance among fluoroquinolones in multidrug-resistant Mycobacterium tuberculosis isolates at a national reference laboratory in India // J. Glob. Antimicrob. Resist. − 2018. − Vol. 12. − P. 5−10. doi: 10.1016/j.jgar.2017.08.014

13. Pang Y., Zong Z., Huo F.et al. In vitro drug susceptibility of bedaquiline, delamanid, linezolid, clofazimine, moxifloxacin, and gatifloxacin against extensively drug-resistant tuberculosis in Beijing, China // Antimicrob. Agents Chemother. − Vol. 61, № 10. – P. e00900-17. doi: 10.1128/AAC.00900-17

14. Sati Н., Carrara E., Savoldi A. et al. The WHO Bacterial Priority Pathogens List, 2024: a prioritization study to guide research, development, and public health strategies against antimicrobial resistance // Lancet Infect. Dis. − 2025. − Vol. 25, № 9. − P. 1033−1043. doi: 10.1016/S1473-3099(25)00118-5.

15. Siddiqi S., Rusch-Gerdes S., Alexander H. et al. MGIT procedure manual for BACTECТМMGITТМ960 TB System (Also applicable for manual MGIT) Mycobacteria Growth Indicator Tube (MGIT) culture and drug susceptibility demonstration projects. – 2006. − 74 c.

16. World Health Organization (2008). Policy guidance on drug-susceptibility testing (DST) of second-line antituberculosis drugs // WHO/HTM/TB/2008.392. – Geneva, 2008.

17. World Health Organization (2014). Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Chapter 3. Laboratory // Geneva: WHO, 2014. − P. 39−60.

18. World Health Organization (2018). Technical report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis / WHO/CDS/TB/2018.5. Licence: CC BY-NC-SA 3.0 IGO. – Geneva: World Health Organization, 2018.

19. World Health Organization (2025). Global tuberculosis report 2025 / https://www.who.int/teams/global-programme-on-tuberculosis-and-lung-health/tb-reports/global-tuberculosis-report-2025

20. Zheng H., He W., Jiao W. et al. Molecular characterization of multidrug-resistant tuberculosis against levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, and delamanid in southwest of China // BMC Infect. Dis. − 2021. − Vol. 21, №1. – P. 330. doi: 10.1186/s12879-021-06024-8