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

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.