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System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

Published on: April 5, 2017

Effectiveness of a bedaquiline, linezolid, clofazimine 'core' for multidrug-resistant TB

C Zeng¹, M A Hernán², L Trevisi¹

¹Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.

|May 14, 2025

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.

Keywords:

MDR-TB endTB observational study fluoroquinolone resistance inverse-probability weighting rifampicin resistance target trial tuberculosis

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