Effectiveness of a bedaquiline, linezolid, clofazimine 'core' for multidrug-resistant TB.
| Title: | Effectiveness of a bedaquiline, linezolid, clofazimine 'core' for multidrug-resistant TB. |
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| Authors: | Zeng C; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.; Hernán MA; CAUSALab, Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Trevisi L; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.; Sauer S; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.; Mitnick CD; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.; Partners In Health (PIH), Boston, MA, USA.; Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA, USA.; Hewison C; Medical Department, Médecins Sans Frontières (MSF), Paris, France.; Bastard M; Field Epidemiology Department, Epicentre, Paris, France.; Khan P; Interactive Research and Development (IRD) Global, Singapore.; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.; Seung KJ; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.; Partners In Health (PIH), Boston, MA, USA.; Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA, USA.; Rich ML; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.; Partners In Health (PIH), Boston, MA, USA.; Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA, USA.; Law S; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.; Kikvidze M; MSF, Sokhumi, Georgia.; Kirakosyan O; MSF, Yerevan, Armenia.; Miankou A; MSF, Minsk, Belarus.; Thit P; MSF, Yangon, Myanmar.; Mamsa S; Indus Hospital & Health Network (IHHN), Karachi, Pakistan.; Janmohamed A; Interactive Research and Development, Karachi, Pakistan.; Melikyan N; Field Epidemiology Department, Epicentre, Paris, France.; Ahmed S; Interactive Research and Development, Karachi, Pakistan.; Vargas D; PIH/Socios En Salud Sucursal Peru, Lima, Peru.; Binegdie AB; Addis Ababa University College of Health Sciences, Department of Internal Medicine, Addis Ababa, Ethiopia.; Temirova K; PIH, Almaty, Kazakhstan.; Oyewusi L; PIH, Lesotho, Maseru, Lesotho.; Philippe K; PIH, Port-au-Prince, Haiti.; Vilbrun SC; Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti.; Khan U; Interactive Research and Development (IRD) Global, Singapore.; Huerga H; Field Epidemiology Department, Epicentre, Paris, France.; Franke MF; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. |
| Source: | IJTLD open [IJTLD Open] 2025 May 12; Vol. 2 (5), pp. 269-275. Date of Electronic Publication: 2025 May 12 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: International Union against Tuberculosis and Lung Disease Country of Publication: France NLM ID: 9918803487706676 Publication Model: eCollection Cited Medium: Internet ISSN: 3005-7590 (Electronic) Linking ISSN: 30057590 NLM ISO Abbreviation: IJTLD Open Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: [Paris, France] : International Union against Tuberculosis and Lung Disease, [2024]- |
| Abstract: | Background: Treatment outcomes may be compromised among individuals with multidrug/rifampicin-resistant TB (MDR/RR-TB) with fluoroquinolone (FQ) resistance. Among people in whom an FQ was unlikely to be effective, we compared the effectiveness of longer individualised regimens comprised of bedaquiline (Bdq) for 5-8 months, linezolid, and clofazimine to those reinforced with at least 1 Group C drug and/or longer Bdq duration.; Methods: We emulated a target trial to compare the effectiveness of initiating and remaining on the core regimen to a regimen reinforced with 1) Bdq for ≥9 months, 2) Bdq for ≥9 months, and delamanid (Dlm), 3) imipenem (Imp), 4) a second-line injectable, or 5) Bdq for ≥9 months, Dlm and Imp. We used cloning, censoring, and inverse-probability weighting to estimate the probabilities of successful treatment.; Results: Adjusted probabilities of successful treatment ranged from 0.75 (95% CI 0.61-0.89) to 0.84 (95% CI 0.76-0.91). Ratios of treatment success ranged from 1.01 for regimens reinforced with Bdq ≥9 months (95% CI 0.79-1.28) and Bdq ≥9 months plus Dlm (95% CI 0.81-1.31) to 1.11 for regimens reinforced with an injectable (95% CI 0.92-1.39) and Bdq ≥9 months, Dlm and Imp (95% CI 0.90-1.41).; Conclusions: Some reinforced regimens had modestly higher treatment success rates, but estimates were imprecise. Additional studies of strategies for maximising treatment success among individuals with FQ resistance are needed.; (© 2025 The Authors.) |
| Competing Interests: | Conflicts of Interest and Source of Funding: Bdq donations made from Janssen (Beerse, Belgium) to the Global Drug Facility were used for patients in the endTB observational study. Donations of Dlm from Otsuka (Tokyo, Japan) were used for initial patients enrolled in the endTB observational study. The donors did not have any role in the study design, data analyses, data interpretation or manuscript writing. |
| Comments: | Update of: medRxiv. 2024 Jan 19:2024.01.18.24301453. doi: 10.1101/2024.01.18.24301453.. (PMID: 38293100) |
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| Grant Information: | R01 AI146095 United States AI NIAID NIH HHS |
| Contributed Indexing: | Keywords: MDR-TB; endTB observational study; fluoroquinolone resistance; inverse-probability weighting; rifampicin resistance; target trial; tuberculosis |
| Entry Date(s): | Date Created: 20250514 Latest Revision: 20260306 |
| Update Code: | 20260306 |
| PubMed Central ID: | PMC12068452 |
| DOI: | 10.5588/ijtldopen.24.0515 |
| PMID: | 40365032 |
| Database: | MEDLINE |
Journal Article