Effectiveness and implementation challenges of short-course all-oral BPaL and BPaLM regimens for drug-resistant tuberculosis: A systematic literature review

DOI: https://doi.org/10.33024/minh.v8i11.1998

Authors

  • Fikria Adiputri Fakultas Farmasi, Universitas Indonesia
  • Rani Sauriasari Fakultas Farmasi, Universitas Indonesia
  • Dewi Danawati Fakultas Farmasi, Universitas Indonesia

BPaL BPaLM Drug-Resistant Implementation Challenges Tuberculosis

Abstract

Background: Drug-resistant tuberculosis (TB-RO), including MDR and XDR forms, remains a major global health burden due to prolonged, toxic, and often ineffective conventional regimens. The introduction of short-course all-oral therapies BPaL (bedaquiline, pretomanid, linezolid) and BPaLM (with moxifloxacin) has offered a promising alternative, with evidence of superior efficacy, safety, and patient adherence. However, implementation across countries continues to face challenges, including limited access to pretomanid, insufficient laboratory capacity, and scarce evidence for special populations.

Purpose: To synthesize global evidence on the effectiveness, implementation challenges, and supporting factors associated with BPaL and BPaLM regimens for drug-resistant tuberculosis.

Method: A Systematic Literature Review (SLR) following the PRISMA protocol was conducted to identify, screen, and include relevant studies published from 2016–2024. Data sources consisted of clinical trials, operational studies, cost-effectiveness analyses, bibliometric reviews, and qualitative stakeholder assessments. Thematic analysis was applied to summarize findings on treatment outcomes, adverse effects, operational barriers, and socio-economic influences that shape implementation across different health system contexts.

Results: Regimens BPaL and BPaLM demonstrated high treatment success rates ranging from 84% to 97.6%, with rapid sputum culture conversion. Linezolid-related toxicities—such as neuropathy and myelosuppression—were common but manageable through dose adjustment and active monitoring. Cost-effectiveness analyses indicated up to a 25% reduction in per-patient expenditure compared with conventional regimens. Supporting factors included patient-centred care, psychosocial support, strengthened pharmacovigilance, and international technical collaboration. Key barriers comprised limited pretomanid access, inadequate laboratory capacity for drug-susceptibility testing, variable readiness of health systems, and limited evidence in special populations (children, pregnant women, and extrapulmonary TB cases).

Conclusion: The global adoption of BPaL and BPaLM regimens marks a significant advancement in the treatment of drug-resistant tuberculosis by enabling shorter, safer, and more cost-effective therapy with consistently high treatment success and improved operational feasibility across diverse settings.

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References

Burhan, E., Sugiharto, J., Soemarno, M., Juan, A., Runtu, Y., Yuvensia, A., & Gebhard, A. (2025). Treatment success rate and time to culture conversion under a prospective BPaL cohort study. IJTLD open, 2(5), 284-290.

Connors, W., Nishi, C., Sekirov, I., Cook, V., & Johnston, J. (2023). Novel six-month all oral treatment of pre-extensively drug-resistant tuberculosis in Canada: New treatment options present new implementation challenges. Canada Communicable Disease Report, 49(1), 15.

Conradie, F., Bagdasaryan, T. R., Borisov, S., Howell, P., Mikiashvili, L., Ngubane, N., & Spigelman, M. (2022). Bedaquiline–pretomanid–linezolid regimens for drug-resistant tuberculosis. New England Journal of Medicine, 387(9), 810-823.

Conradie, F., Diacon, A. H., Ngubane, N., Howell, P., Everitt, D., Crook, A. M., & Spigelman, M. (2020). Treatment of highly drug-resistant pulmonary tuberculosis. New England Journal of Medicine, 382(10), 893-902.

Evans, D., Hirasen, K., Casalme, D. J., Gler, M. T., Gupta, A., & Juneja, S. (2024). Cost and cost-effectiveness of BPaL regimen used in drug-resistant TB treatment in the Philippines. IJTLD open, 1(6), 242-249.

Feshchenko, Y. I., Lytvynenko, N. A., Pohrebna, M. V, Senko, Y. O., Lafeta, A. S., Lyubevych, R. L., Gamazin, Y. О., & Terleeva, Y. S. (2023). BPаL: the first program results of operational study within the framework of the project ICF «Оrganization for Appropriate Technology in Health» and facilitating the expansion this regimen in Ukraine. Tuberculosis, Lung Diseases, HIV Infection, 2023(1), 5–10. Retrieved from: http://tubvil.com.ua/article/view/275368

Gomez, G. B., Siapka, M., Conradie, F., Ndjeka, N., Garfin, A. M. C., Lomtadze, N., & Vassall, A. (2021). Cost-effectiveness of bedaquiline, pretomanid and linezolid for treatment of extensively drug-resistant tuberculosis in South Africa, Georgia and the Philippines. BMJ open, 11(12), e051521.

Gupta, A., Juneja, S., Babawale, V., Majidovich, N. R., Ndjeka, N., Nguyen, P. T. M., & Sahu, S. (2024). Global adoption of 6-month drug-resistant TB regimens: projected uptake by 2026. PLoS One, 19(1), e0296448.

Haley, C. A., Schechter, M. C., Ashkin, D., Peloquin, C. A., Peter Cegielski, J., Andrino, B. B., & Goswami, N. D. (2023). Implementation of bedaquiline, pretomanid, and linezolid in the United States: experience using a novel all-oral treatment regimen for treatment of rifampin-resistant or rifampin-intolerant tuberculosis disease. Clinical Infectious Diseases, 77(7), 1053-1062.

Hasan, T., Medcalf, E., Nyang'wa, B. T., Egizi, E., Berry, C., Dodd, M., & Fox, G. (2024). The safety and tolerability of linezolid in novel short-course regimens containing bedaquiline, pretomanid, and linezolid to treat rifampicin-resistant tuberculosis: an individual patient data meta-analysis. Clinical Infectious Diseases, 78(3), 730-741.

Horter, S., Stringer, B., Gray, N., Parpieva, N., Safaev, K., Tigay, Z., & Achar, J. (2020). Person-centred care in practice: perspectives from a short course regimen for multi-drug resistant tuberculosis in Karakalpakstan, Uzbekistan. BMC Infectious Diseases, 20(1), 675.

Ikpe, G., Dimang, S., Aduh, U., Omoniyi, P. I., Chukwulobelu, U., Okafor, C., & Nwokocha, G. (2025). Treatment outcomes among patients with drug-resistant tuberculosis managed with BPaL/BPaLM regimen in the Southeast Zone of Nigeria. The Pan African Medical Journal, 51, 86.

Khan, M. A., Ismail, A., Ghafoor, A., Khan, N., Muzaffar, N., Zafar, F., & Shahid, S. (2024). Experience of piloting BPaLM/BPaL for DR-TB care at selected sites in Pakistan. IJTLD open, 1(11), 508-515.

Myrzaliev, B., Ahmatov, M., Duishekeeva, A., Kulzhabaeva, A., Kadyrov, A., Toktogonova, A., & Gebhard, A. (2024). Experiences in the introduction of bedaquiline pretomanid linezolid for drug-resistant tuberculosis in Kyrgyzstan. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 36, 100472.

Nyang’wa, B. T., Berry, C., Kazounis, E., Motta, I., Parpieva, N., Tigay, Z., & Fielding, K. (2022). A 24-week, all-oral regimen for rifampin-resistant tuberculosis. New England Journal of Medicine, 387(25), 2331-2343.

Otto-Knapp, R., Edwards, S., Kuchukhidze, G., Kröger, S., Häcker, B., Bivol, S., & Yedilbayev, A. (2024). Availability of drugs for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis in the World Health Organization European Region, October 2023. Eurosurveillance, 29(17), 2400211.

Porter, M. E. (2010). What is value in health care?. New England Journal of Medicine, 363(26), 2477-2481.

Rashitov, M., Franke, M. F., Trevisi, L., Bekbolatova, G., Shalimova, J., Eshmetov, G., & Rich, M. L. (2024). Safety and Effectiveness of 3 Novel All-Oral Shortened Regimens for Rifampicin-or Multidrug-Resistant Tuberculosis in Kazakhstan. Clinical Infectious Diseases, 79(4), 1046-1053.

Sangsayunh, P., Sanchat, T., Chuchottaworn, C., Cheewakul, K., & Rattanawai, S. (2024). The use of BPaL containing regimen in the MDR/PreXDR TB treatments in Thailand. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 34, 100408.

Silva, D. R., Fernandes, F. F., Ferreira, J. C., Bernando, W., Dalcolmo, M. M. P., Johansen, F. D. C., & Mello, F. C. Q. (2024). Bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) for multidrug-or rifampin-resistant tuberculosis: a systematic review. Brazilian Journal of Pulmonology/Jornal Brasileiro de Pneumologia, 50(6).

Sinha, A., Klebe, R., Rekart, M. L., Alvarez, J. L., Skrahina, A., Yatskevich, N., & Saunders, M. J. (2025). The Effectiveness and Safety of Bedaquiline, Pretomanid, and Linezolid (BPaL)–Based Regimens for Rifampicin-Resistant Tuberculosis in Non-Trial Settings—A Prospective Cohort Study in Belarus and Uzbekistan. Clinical Infectious Diseases, ciaf035.

Sridharan, K., & Sivaramakrishnan, G. (2025). Global research trends in BPaL and BPaLM regimens for drug-resistant tuberculosis: a bibliometric analysis. Tropical Diseases, Travel Medicine and Vaccines, 11(1), 33.

Van De Berg, S. E. J., Pelzer, P. T., Van Der Land, A. J., Abdrakhmanova, E., Ozi, A. M., Arias, M., & van den Hof, S. (2021). Acceptability, feasibility, and likelihood of stakeholders implementing the novel BPaL regimen to treat extensively drug-resistant tuberculosis patients. BMC Public Health, 21(1), 1404.

Vanino, E., Granozzi, B., Akkerman, O. W., Munoz-Torrico, M., Palmieri, F., Seaworth, B., & Tadolini, M. (2023). Update of drug-resistant tuberculosis treatment guidelines: A turning point. International Journal of Infectious Diseases, 130, S12-S15.

World Health Organization. (2022). Rapid communication: key changes to the treatment of drug-resistant tuberculosis. World Health Organization (Issue WHO/UCN/TB/2022.2.). Retrieved from: https://www.who.int/publications/i/item/WHO-UCN-TB-2022-2.

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Published

2026-01-31

How to Cite

Effectiveness and implementation challenges of short-course all-oral BPaL and BPaLM regimens for drug-resistant tuberculosis: A systematic literature review. (2026). MIN, 8(11), 1464-1475. https://doi.org/10.33024/minh.v8i11.1998