The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Treatment of Highly Drug-Resistant Pulmonary Tuberculosis
Open accessAbstract
BACKGROUND: Patients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes. METHODS: In an open-label, single-group study in which follow-up is ongoing at three South African sites, we investigated treatment with three oral drugs - bedaquiline, pretomanid, and linezolid - that have bactericidal activity against tuberculosis and to which there is little preexisting resistance. We evaluated the safety and efficacy of the drug combination for 26 weeks in patients with extensively drug-resistant tuberculosis and patients with multidrug-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. The primary end point was the incidence of an unfavorable outcome, defined as treatment failure (bacteriologic or clinical) or relapse during follow-up, which continued until 6 months after the end of treatment. Patients were classified as having a favorable outcome at 6 months if they had resolution of clinical disease, a negative culture status, and had not already been classified as having had an unfavorable outcome. Other efficacy end points and safety were also evaluated. RESULTS: A total of 109 patients were enrolled in the study and were included in the evaluation of efficacy and safety end points. At 6 months after the end of treatment in the intention-to-treat analysis, 11 patients (10%) had an unfavorable outcome and 98 patients (90%; 95% confidence interval, 83 to 95) had a favorable outcome. The 11 unfavorable outcomes were 7 deaths (6 during treatment and 1 from an unknown cause during follow-up), 1 withdrawal of consent during treatment, 2 relapses during follow-up, and 1 loss to follow-up. The expected linezolid toxic effects of peripheral neuropathy (occurring in 81% of patients) and myelosuppression (48%), although common, were manageable, often leading to dose reductions or interruptions in treatment with linezolid. CONCLUSIONS: The combination of bedaquiline, pretomanid, and linezolid led to a favorable outcome at 6 months after the end of therapy in a high percentage of patients with highly drug-resistant forms of tuberculosis; some associated toxic effects were observed. (Funded by the TB Alliance and others; ClinicalTrials.gov number, NCT02333799.).
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A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis
Stover, C. K., Warrener, P., VanDevanter, D. R., Sherman, D. R., Arain, T. M., Langhorne, M. H., Anderson, S. W., Towell, J. A., Yuan, Y., McMurray, D. N., et al. (2000) · Nature · doi:10.1038/35016103 · Cited by 1,034
Four-Month Moxifloxacin-Based Regimens for Drug-Sensitive Tuberculosis
Gillespie, S. H., Crook, A. M., McHugh, T. D., Mendel, C. M., Meredith, S. K., Murray, S. R., Pappas, F., Phillips, P. P. J., & Nunn, A. J. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407426 · Cited by 645
Self-citationAhmad, N., Ahuja, S. D., Akkerman, O. W., Alffenaar, J.-W. C., Anderson, L. F., Baghaei, P., Bang, D., Barry, P. M., Bastos, M. L., Behera, D., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31644-1 · Cited by 632
PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release
Singh, R., Manjunatha, U., Boshoff, H. I. M., Ha, Y. H., Niyomrattanakit, P., Ledwidge, R., Dowd, C. S., Lee, I. Y., Kim, P., Zhang, L., et al. (2008) · Science · doi:10.1126/science.1164571 · Cited by 628
Linezolid for Treatment of Chronic Extensively Drug-Resistant Tuberculosis
Lee, M., Lee, J., Carroll, M. W., Choi, H., Min, S., Song, T., Via, L. E., Goldfeder, L. C., Kang, E., Jin, B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1201964 · Cited by 560
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Self-citationHigh-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis
Jindani, A., Harrison, T. S., Nunn, A. J., Phillips, P. P. J., Churchyard, G. J., Charalambous, S., Hatherill, M., Geldenhuys, H., McIlleron, H. M., Zvada, S. P., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1314210 · Cited by 432
Self-citationA Four-Month Gatifloxacin-Containing Regimen for Treating Tuberculosis
Merle, C. S., Fielding, K., Sow, O. B., Gninafon, M., Lo, M. B., Mthiyane, T., Odhiambo, J., Amukoye, E., Bah, B., Kassa, F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1315817 · Cited by 399
A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis
Nunn, A. J., Phillips, P. P. J., Meredith, S. K., Chiang, C.-Y., Conradie, F., Dalai, D., van Deun, A., Dat, P.-T., Lan, N., Master, I., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1811867 · Cited by 390
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Cited by
Bedaquiline–Pretomanid–Linezolid Regimens for Drug-Resistant Tuberculosis
Conradie, F., Bagdasaryan, T. R., Borisov, S., Howell, P., Mikiashvili, L., Ngubane, N., Samoilova, A., Skornykova, S., Tudor, E., Variava, E., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2119430 · Cited by 578
Self-citationAnti-tuberculosis treatment strategies and drug development: challenges and priorities
Dartois, V. A., & Rubin, E. J. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00731-y · Cited by 490
Mirzayev, F., Viney, K., Linh, N. N., Gonzalez-Angulo, L., Gegia, M., Jaramillo, E., Zignol, M., & Kasaeva, T. (2021) · European Respiratory Journal · doi:10.1183/13993003.03300-2020 · Cited by 301
Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline
Guo, H., Courbon, G. M., Bueler, S. A., Mai, J., Liu, J., & Rubinstein, J. L. (2021) · Nature · doi:10.1038/s41586-020-3004-3 · Cited by 200
Scientific advances and the end of tuberculosis: a report from the Lancet Commission on Tuberculosis
Reid, M., Agbassi, Y. J. P., Arinaminpathy, N., Bercasio, A., Bhargava, A., Bhargava, M., Bloom, A., Cattamanchi, A., Chaisson, R., Chin, D., et al. (2023) · The Lancet · doi:10.1016/s0140-6736(23)01379-x · Cited by 87
Metadata
- Authors
- Conradie, F., Diacon, A. H., Ngubane, N., Howell, P., Everitt, D., Crook, A. M., Mendel, C. M., Egizi, E., Moreira, J., Timm, J., McHugh, T. D., Wills, G. H., Bateson, A., Hunt, R., Van Niekerk, C., Li, M., Olugbosi, M., & Spigelman, M.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-03-05
- Volume
- 382
- Issue
- 10
- Pages
- 893-902
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3009599329
- Cited by
- 1,044
- References
- 19
- FWCI
- 16.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Conradie, F., Diacon, A. H., Ngubane, N., Howell, P., Everitt, D., Crook, A. M., Mendel, C. M., Egizi, E., Moreira, J., Timm, J., McHugh, T. D., Wills, G. H., Bateson, A., Hunt, R., Van Niekerk, C., Li, M., Olugbosi, M., & Spigelman, M. (2020). Treatment of Highly Drug-Resistant Pulmonary Tuberculosis. New England Journal of Medicine. https://doi.org/10.1056/nejmoa1901814
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