Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Feb;80(1):98-105.
doi: 10.1002/ddr.21498. Epub 2018 Dec 11.

Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: Promising but challenging

Yang Li  1 , Feng Sun  1 , Wenhong Zhang  1   2
Affiliations
Review

Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: Promising but challenging

Yang Li et al. Drug Dev Res. 2019 Feb.

Abstract

Improving treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) is partly hampered by inadequate effective antitubercular agents. Development of bedaquiline and delamanid has potentially changed the treatment landscape for MDR-TB. This review provides an update on the progress of these novel antitubercular agents. We review published studies aimed at evaluating clinical efficacy and effectiveness of bedaquiline and delamanid. Five prospective clinical studies and seven retrospective studies on bedaquiline showed that patients treated with a bedaquiline-containing regimen had a high culture conversion rate ranging from 65 to 100% and a satisfactory treatment outcome. The combined use with linezolid might add to the effectiveness of bedaquiline. Controversies about bedaquiline resistance are discussed. Three clinical trials have reported outcomes on delamanid and showed that introducing delamanid to a background regimen improved culture conversion rate at 2 months from 29.6% to more than 40%. A higher favorable treatment rate was also observed among patients who received delamanid for more than 6 months, but about a quarter of patients defaulted in the control group. Seven retrospective studies were summarized and found a treatment benefit as well. More reliable evidence from randomized clinical trials reporting on the treatment outcomes is needed urgently to support a strong recommendation for the use of delamanid. Advances in the combined use of bedaquiline and delamanid are also reviewed, and the combination may be well tolerated but requires electrocardiograph monitoring.

Keywords: bedaquiline; delamanid; multidrug-resistant tuberculosis.

PubMed Disclaimer

Conflict of interest statement

We declare no competing interests.

Figures

Figure 1
Figure 1
Summary of prospective and retrospective studies reporting on the sputum conversion rate at week 24 among patients treated with the bedaquiline‐containing regimen. Each circle represents one clinical study, and spotted circles were retrospective studies. The number in the middle of circle is the sample size enrolled into studies. The shade of color represents the proportion of patients with XDR‐TB in the study, like the circle in indigo blue means that the corresponding study only enrolled patients with XDR‐TB and the circle in red means that all participants were simple MDR‐TB. MDR‐TB = multidrug‐resistant tuberculosis; XDR‐TB = extensively drug‐resistant tuberculosis
See this image and copyright information in PMC

References

    1. Andries, K. , Verhasselt, P. , Guillemont, J. , Göhlmann, H. W. H. , Neefs, J. M. , Winkler, H. , … Jarlier, V. (2005). A diarylquinoline drug active on the ATP synthase of mycobacterium tuberculosis. Science, 307(5707), 223–227. 10.1126/science.1106753 - DOI - PubMed
    1. Bloemberg, G. V. , Keller, P. M. , Stucki, D. , Trauner, A. , Borrell, S. , Latshang, T. , … Böttger, E. C. (2015). Acquired resistance to bedaquiline and delamanid in therapy for tuberculosis. New England Journal of Medicine, 373(20), 1986–1988. 10.1056/NEJMc1505196 - DOI - PMC - PubMed
    1. Borisov, S. E. , Dheda, K. , Enwerem, M. , Leyet, R. R. , D'Ambrosio, L. , Centis, R. , … Migliori, G. B. (2017). Effectiveness and safety of bedaquilinecontaining regimens in the treatment of MDR‐ and XDR‐TB: A multicentre study. European Respiratory Journal, 49(5), 1700387 10.1183/13993003.00387-2017 - DOI - PubMed
    1. Caminero, J. A. , Piubello, A. , Scardigli, A. , & Migliori, G. B. (2017). Bedaquiline: How better to use it. European Respiratory Journal, 50(5), 1701670. Retrieved from http://erj.ersjournals.com/content/50/5/1701670.abstract - PubMed
    1. Cegielski, J. P. , Dalton, T. , Yagui, M. , Wattanaamornkiet, W. , Volchenkov, G. V. , Via, L. E. , … Akksilp, S. (2014). Extensive drug resistance acquired during treatment of multidrug‐resistant tuberculosis. Clinical Infectious Diseases, 59(8), 1049–1063. 10.1093/cid/ciu572 - DOI - PMC - PubMed

MeSH terms