Effectiveness of a bedaquiline, linezolid, clofazimine ‘core’ for multidrug-resistant TB
Zeng C. Hernán M.A. Trevisi L. Sauer S. Mitnick C.D. Hewison C. Bastard M. Khan P. Seung K.J. Rich M.L. Law S. Kikvidze M. Kirakosyan O. Miankou A. Thit P. Mamsa S. Janmohamed A. Melikyan N. Ahmed S. Vargas D. Binegdie A.B. Temirova K. Oyewusi L. Philippe K. Vilbrun S.C. Khan U. Huerga H. Franke M.F.
9 May 2025International Union Against Tuberculosis and Lung Disease
IJTLD Open
2025#2Issue 5269 - 275 pp.
BACKGROUND: Treatment outcomes may be compro-mised 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 indi-vidualised 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 in-jectable (95% CI 0.92–1.39) and Bdq ≥9 months, Dlm and Imp (95% CI 0.90–1.41). CONCLUSIONS: Some reinforced regimens had mod-estly higher treatment success rates, but estimates were imprecise. Additional studies of strategies for maximising treatment success among individuals with FQ resistance are needed.
endTB observational study , fluoroquinolone resistance , inverse-probability weighting , MDR-TB , rifampicin resistance , target trial , tuberculosis
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Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, United States
CAUSALab, Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States
Partners In Health (PIH), Boston, MA, United States
Division of Global Health Equity, Brigham and Women’s Hospital, Boston, MA, United States
Medical Department, Médecins Sans Frontières (MSF), Paris, France
Field Epidemiology Department, Epicentre, Paris, France
Interactive Research and Development (IRD) Global, Singapore
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
MSF, Sokhumi, Georgia
MSF, Yerevan, Armenia
MSF, Minsk, Belarus
MSF, Yangon, Myanmar
Indus Hospital & Health Network (IHHN), Karachi, Pakistan
Interactive Research and Development, Karachi, Pakistan
PIH/Socios En Salud Sucursal Peru, Lima, Peru
Addis Ababa University College of Health Sciences, Department of Internal Medicine, Addis Ababa, Ethiopia
PIH, Almaty, Kazakhstan
PIH, Maseru, Lesotho
PIH, Port-au-Prince, Haiti
Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
Department of Global Health and Social Medicine
CAUSALab
Partners In Health (PIH)
Division of Global Health Equity
Medical Department
Field Epidemiology Department
Interactive Research and Development (IRD) Global
Department of Clinical Research
MSF
MSF
MSF
MSF
Indus Hospital & Health Network (IHHN)
Interactive Research and Development
PIH/Socios En Salud Sucursal Peru
Addis Ababa University College of Health Sciences
PIH
PIH
PIH
Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO)
Department of Epidemiology
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