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Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts
BACKGROUND: There are no data comparing the 6–9 month oral three-drug Nix regimen (bedaquiline, pretomanid and linezolid [BPaL]) to conventional regimens containing bedaquiline (B, BDQ) and linezolid (L, LZD). METHODS: Six-month post end-of-treatment outcomes were compared between Nix-TB (n = 109) a...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union Against Tuberculosis and Lung Disease
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171246/ https://www.ncbi.nlm.nih.gov/pubmed/34049607 http://dx.doi.org/10.5588/ijtld.21.0035 |
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author | Oelofse, S. Esmail, A. Diacon, A. H. Conradie, F. Olayanju, O. Ngubane, N. Howell, P. Everitt, D. Crook, A. M. Mendel, C. M. Wills, G. H. Olugbosi, M. del Parigi, A. Sun, E. Calatroni, A. Spigelman, M. Dheda, K. |
author_facet | Oelofse, S. Esmail, A. Diacon, A. H. Conradie, F. Olayanju, O. Ngubane, N. Howell, P. Everitt, D. Crook, A. M. Mendel, C. M. Wills, G. H. Olugbosi, M. del Parigi, A. Sun, E. Calatroni, A. Spigelman, M. Dheda, K. |
author_sort | Oelofse, S. |
collection | PubMed |
description | BACKGROUND: There are no data comparing the 6–9 month oral three-drug Nix regimen (bedaquiline, pretomanid and linezolid [BPaL]) to conventional regimens containing bedaquiline (B, BDQ) and linezolid (L, LZD). METHODS: Six-month post end-of-treatment outcomes were compared between Nix-TB (n = 109) and 102 prospectively recruited extensively drug-resistant TB patients who received an ~18-month BDQ-based regimen (median of 8 drugs). A subset of patients received BDQ and LZD (n = 86), and a subgroup of these (n = 75) served as individually matched controls in a pairwise comparison to determine differences in regimen efficacy. RESULTS: Favourable outcomes (%) were significantly better with BPaL than with the B–L-based combination regimen (98/109, 89.9% vs. 56/86, 65.1%; adjusted relative risk ratio [aRRR] 1.35; P < 0.001) and in the matched pairwise analysis (67/75, 89.3% vs. 48/75, 64.0%; aRRR 1.39; P = 0.001), despite significantly higher baseline bacterial load and prior second-line drug exposure in the BPaL cohort. Time to culture conversion (P < 0.001), time to unfavourable outcome (P < 0.01) and time to death (P < 0.03) were significantly better or lower with BPaL than the B-L-based combinations. CONCLUSION: The BPaL regimen (and hence substitution of multiple other drugs by pretomanid and/or higher starting-dose LZD) may improve outcomes in drug-resistant TB patients with poor prognostic features. However, prospective controlled studies are required to definitively answer this question. |
format | Online Article Text |
id | pubmed-8171246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | International Union Against Tuberculosis and Lung Disease |
record_format | MEDLINE/PubMed |
spelling | pubmed-81712462021-06-02 Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts Oelofse, S. Esmail, A. Diacon, A. H. Conradie, F. Olayanju, O. Ngubane, N. Howell, P. Everitt, D. Crook, A. M. Mendel, C. M. Wills, G. H. Olugbosi, M. del Parigi, A. Sun, E. Calatroni, A. Spigelman, M. Dheda, K. Int J Tuberc Lung Dis Original Articles BACKGROUND: There are no data comparing the 6–9 month oral three-drug Nix regimen (bedaquiline, pretomanid and linezolid [BPaL]) to conventional regimens containing bedaquiline (B, BDQ) and linezolid (L, LZD). METHODS: Six-month post end-of-treatment outcomes were compared between Nix-TB (n = 109) and 102 prospectively recruited extensively drug-resistant TB patients who received an ~18-month BDQ-based regimen (median of 8 drugs). A subset of patients received BDQ and LZD (n = 86), and a subgroup of these (n = 75) served as individually matched controls in a pairwise comparison to determine differences in regimen efficacy. RESULTS: Favourable outcomes (%) were significantly better with BPaL than with the B–L-based combination regimen (98/109, 89.9% vs. 56/86, 65.1%; adjusted relative risk ratio [aRRR] 1.35; P < 0.001) and in the matched pairwise analysis (67/75, 89.3% vs. 48/75, 64.0%; aRRR 1.39; P = 0.001), despite significantly higher baseline bacterial load and prior second-line drug exposure in the BPaL cohort. Time to culture conversion (P < 0.001), time to unfavourable outcome (P < 0.01) and time to death (P < 0.03) were significantly better or lower with BPaL than the B-L-based combinations. CONCLUSION: The BPaL regimen (and hence substitution of multiple other drugs by pretomanid and/or higher starting-dose LZD) may improve outcomes in drug-resistant TB patients with poor prognostic features. However, prospective controlled studies are required to definitively answer this question. International Union Against Tuberculosis and Lung Disease 2021-06-01 2021-06-01 /pmc/articles/PMC8171246/ /pubmed/34049607 http://dx.doi.org/10.5588/ijtld.21.0035 Text en © 2021 The Union https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Original Articles Oelofse, S. Esmail, A. Diacon, A. H. Conradie, F. Olayanju, O. Ngubane, N. Howell, P. Everitt, D. Crook, A. M. Mendel, C. M. Wills, G. H. Olugbosi, M. del Parigi, A. Sun, E. Calatroni, A. Spigelman, M. Dheda, K. Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts |
title | Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts |
title_full | Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts |
title_fullStr | Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts |
title_full_unstemmed | Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts |
title_short | Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts |
title_sort | pretomanid with bedaquiline and linezolid for drug-resistant tb: a comparison of prospective cohorts |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171246/ https://www.ncbi.nlm.nih.gov/pubmed/34049607 http://dx.doi.org/10.5588/ijtld.21.0035 |
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