Bedaquiline resistance in Mycobacterium tuberculosis during antimycobacterial therapy and its impact on clinical outcomes (clinical cases)

Authors

DOI:

https://doi.org/10.14739/2310-1210.2023.1.268009

Keywords:

multidrug-resistant tuberculosis, bedaquiline, results

Abstract

Aim. To analyze the nature of Bedaquiline (Bdq) resistance in Mycobacterium tuberculosis (MBT) during antimycobacterial therapy (AMBT) in patients with multidrug-resistant tuberculosis (MDR-TB), its impact on clinical outcomes and to detect risk factors for the Bdq drug resistance development on the example of own observed clinical cases.

Materials and methods. 2 clinical cases of own observations of the Bdq resistance development in MBT during AMBT in patients with MDR-TB who were treated at the clinical base of the Department of Phthisiology and Pulmonology of Zaporizhzhia State Medical University – Pulmonary Tuberculosis Department No. 2 of the Communal Non-profit Organization “Zaporizhzhia Regional Phthisio-Pulmonology Clinical Treatment and Diagnostic Center” are presented.

Results. The presented clinical cases confirm the literature data that the treatment effectiveness in patients with Rifampicin-resistant TB (RR-TB) and MDR-TB is associated with Bdq drug resistance. Regarding the reasons for the development of acquired Bdq drug resistance, the second clinical case, like the examples of other authors, demonstrates low adherence to treatment. There is no data in the literature about the lack of controlled treatment at the outpatient stage as a risk factor for Bdq drug resistance and negative clinical outcomes in patients with MDR-TB, which would complement the scientific experience in this problem.

Conclusions. In both clinical cases, Bdq drug resistance was acquired (secondary), and had an impact on the clinical outcomes of tuberculosis treatment. The risk factors for Bdq drug resistance and negative clinical outcomes were lack of controlled treatment at the outpatient stage in the first case and low adherence to treatment in the second one.

Author Biographies

O. M. Raznatovska, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Phthisiology and Pulmonology

R. M. Yasinskyi, Zaporizhzhia State Medical University, Ukraine

MD, PhD, Associate Professor of the Department of Phthisiology and Pulmonology

O. S. Shalmin, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor of the Department of Phthisiology and Pulmonology

A. V. Fedorets, Zaporizhzhia State Medical University, Ukraine

MD, Assistant of the Department of Phthisiology and Pulmonology

O. A. Svitlytska, Zaporizhzhia State Medical University, Ukraine

MD, PhD, Assistant of the Department of Phthisiology and Pulmonology

References

Patel H., Pawara R., Pawara K., Ahmed F., Shirkhedkar A., Surana S. (2019). A structural insight of bedaquiline for the cardiotoxicity and hepatotoxicity. Tuberculosis (Edinb), 117, 79-84. https://doi.org/10.1016/j.tube.2019.06.005

Mallick, J. S., Nair, P., Abbew, E. T., Van Deun, A., & Decroo, T. (2022). Acquired bedaquiline resistance during the treatment of drug-resistant tuberculosis: a systematic review. JAC-antimicrobial resistance, 4(2), dlac029. https://doi.org/10.1093/jacamr/dlac029

Liu, Y., Gao, J., Du, J., Shu, W., Wang, L., Wang, Y., Xue, Z., Li, L., Xu, S., & Pang, Y. (2021). Acquisition of clofazimine resistance following bedaquiline treatment for multidrug-resistant tuberculosis. International journal of infectious diseases : IJID, 102, 392-396. https://doi.org/10.1016/j.ijid.2020.10.081

Guglielmetti, L., Chiesi, S., Eimer, J., Dominguez, J., Masini, T., Varaine, F., Veziris, N., Ader, F., & Robert, J. (2020). Bedaquiline and delamanid for drug-resistant tuberculosis: a clinician's perspective. Future microbiology, 15, 779-799. https://doi.org/10.2217/fmb-2019-0309

Nguyen, T. V. A., Anthony, R. M., Bañuls, A. L., Nguyen, T. V. A., Vu, D. H., & Alffenaar, J. C. (2018). Bedaquiline Resistance: Its Emergence, Mechanism, and Prevention. Clinical infectious diseases, 66(10), 1625-1630. https://doi.org/10.1093/cid/cix992

Khoshnood, S., Goudarzi, M., Taki, E., Darbandi, A., Kouhsari, E., Heidary, M., Motahar, M., Moradi, M., & Bazyar, H. (2021). Bedaquiline: Current status and future perspectives. Journal of global antimicrobial resistance, 25, 48-59. https://doi.org/10.1016/j.jgar.2021.02.017

Chiang, C. Y., & Lin, C. J. (2020). Principles of chemotherapy for tuberculosis in national tuberculosis programmes of low- and middle-income countries. The Indian journal of tuberculosis, 67(4S), S16-S22. https://doi.org/10.1016/j.ijtb.2020.11.010

Kempker, R. R., Mikiashvili, L., Zhao, Y., Benkeser, D., Barbakadze, K., Bablishvili, N., Avaliani, Z., Peloquin, C. A., Blumberg, H. M., & Kipiani, M. (2020). Clinical Outcomes Among Patients With Drug-resistant Tuberculosis Receiving Bedaquiline- or Delamanid-Containing Regimens. Clinical infectious diseases, 71(9), 2336-2344. https://doi.org/10.1093/cid/ciz1107

Migliori, G. B., Pontali, E., Sotgiu, G., Centis, R., D'Ambrosio, L., Tiberi, S., Tadolini, M., & Esposito, S. (2017). Combined Use of Delamanid and Bedaquiline to Treat Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: A Systematic Review. International journal of molecular sciences, 18(2), 341. https://doi.org/10.3390/ijms18020341

Franke, M. F., Khan, P., Hewison, C., Khan, U., Huerga, H., Seung, K. J., Rich, M. L., Zarli, K., Samieva, N., Oyewusi, L., Nair, P., Mudassar, M., Melikyan, N., Lenggogeni, P., Lecca, L., Kumsa, A., Khan, M., Islam, S., Hussein, K., Docteur, W., … Mitnick, C. D. (2021). Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid. A Prospective Multicountry Study. American journal of respiratory and critical care medicine, 203(1), 111-119. https://doi.org/10.1164/rccm.202001-0135OC

Gao, J., Pei, Y., Yan, X., Shi, G., Li, T., Gao, M., Liu, Y., Wang, Y., Shu, W., Li, L., & Pang, Y. (2020). Emergence of nontuberculous mycobacteria infections during bedaquiline-containing regimens in multidrug-resistant tuberculosis patients. International journal of infectious diseases : IJID, 100, 196-198. https://doi.org/10.1016/j.ijid.2020.08.080

Ismail, N., Rivière, E., Limberis, J., Huo, S., Metcalfe, J. Z., Warren, R. M., & Van Rie, A. (2021). Genetic variants and their association with phenotypic resistance to bedaquiline in Mycobacterium tuberculosis: a systematic review and individual isolate data analysis. The Lancet. Microbe, 2(11), e604-e616. https://doi.org/10.1016/s2666-5247(21)00175-0

Degiacomi, G., Sammartino, J. C., Sinigiani, V., Marra, P., Urbani, A., & Pasca, M. R. (2020). In vitro Study of Bedaquiline Resistance in Mycobacterium tuberculosis Multi-Drug Resistant Clinical Isolates. Frontiers in microbiology, 11, 559469. https://doi.org/10.3389/fmicb.2020.559469

Ismail, N., Ismail, N. A., Omar, S. V., & Peters, R. P. H. (2019). In Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline Resistance. Antimicrobial agents and chemotherapy, 63(8), e00292-19. https://doi.org/10.1128/AAC.00292-19

Mishra, G. P., & Mulani, J. (2022). Implications of bedaquiline-resistant tuberculosis. The Lancet. Infectious diseases, 22(2), 166. https://doi.org/10.1016/S1473-3099(22)00007-X

He, W., Liu, C., Liu, D., Ma, A., Song, Y., He, P., Bao, J., Li, Y., Zhao, B., Fan, J., Cheng, Q., & Zhao, Y. (2021). Prevalence of Mycobacterium tuberculosis resistant to bedaquiline and delamanid in China. Journal of global antimicrobial resistance, 26, 241-248. https://doi.org/10.1016/j.jgar.2021.06.007

Wu, S. H., Chan, H. H., Hsiao, H. C., & Jou, R. (2021). Primary Bedaquiline Resistance Among Cases of Drug-Resistant Tuberculosis in Taiwan. Frontiers in microbiology, 12, 754249. https://doi.org/10.3389/fmicb.2021.754249

Xu, J., Wang, B., Hu, M., Huo, F., Guo, S., Jing, W., Nuermberger, E., & Lu, Y. (2017). Primary Clofazimine and Bedaquiline Resistance among Isolates from Patients with Multidrug-Resistant Tuberculosis. Antimicrobial agents and chemotherapy, 61(6), e00239-17. https://doi.org/10.1128/AAC.00239-17

World Health Organization. (2022). Rapid communication: key changes to the treatment of drug-resistant tuberculosis. (WHO/UCN/TB/2022.2). Licence: CC BY-NC-SA 3.0 IGO.

Liu, Y., Gao, M., Du, J., Wang, L., Gao, J., Shu, W., Wang, Y., Xue, Z., Li, L., & Pang, Y. (2021). Reduced Susceptibility of Mycobacterium tuberculosis to Bedaquiline During Antituberculosis Treatment and Its Correlation With Clinical Outcomes in China. Clinical infectious diseases, 73(9), e3391-e3397. https://doi.org/10.1093/cid/ciaa1002

Khan, U., Huerga, H., Khan, A. J., Mitnick, C. D., Hewison, C., Varaine, F., Bastard, M., Rich, M., Franke, M. F., Atwood, S., Khan, P. Y., & Seung, K. J. (2019). The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens. BMC infectious diseases, 19(1), 733. https://doi.org/10.1186/s12879-019-4378-4

Saeed, D. K., Shakoor, S., Razzak, S. A., Hasan, Z., Sabzwari, S. F., Azizullah, Z., Kanji, A., Nasir, A., Shafiq, S., Ghanchi, N. K., & Hasan, R. (2022). Variants associated with Bedaquiline (BDQ) resistance identified in Rv0678 and efflux pump genes in Mycobacterium tuberculosis isolates from BDQ naïve TB patients in Pakistan. BMC microbiology, 22(1), 62. https://doi.org/10.1186/s12866-022-02475-4

Guo, Q., Bi, J., Lin, Q., Ye, T., Wang, Z., Wang, Z., Liu, L., & Zhang, G. (2022). Whole Genome Sequencing Identifies Novel Mutations Associated With Bedaquiline Resistance in Mycobacterium tuberculosis. Frontiers in cellular and infection microbiology, 12, 807095. https://doi.org/10.3389/fcimb.2022.807095

Downloads

Published

2023-03-06

How to Cite

1.
Raznatovska OM, Yasinskyi RM, Shalmin OS, Fedorets AV, Svitlytska OA. Bedaquiline resistance in Mycobacterium tuberculosis during antimycobacterial therapy and its impact on clinical outcomes (clinical cases). Zaporozhye medical journal [Internet]. 2023Mar.6 [cited 2024Mar.29];25(1):87-96. Available from: http://zmj.zsmu.edu.ua/article/view/268009