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
Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
CAUSALab, Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
IJTLD Open. 2025 May 12;2(5):269-275. doi: 10.5588/ijtldopen.24.0515. eCollection 2025 May.
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.
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.
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).
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.
耐多药/利福平耐药结核病（MDR/RR-TB）且对氟喹诺酮（FQ）耐药的个体治疗效果可能不佳。在FQ不太可能有效的人群中，我们比较了由5 - 8个月的贝达喹啉（Bdq）、利奈唑胺和氯法齐明组成的较长个体化方案与至少加用1种C组药物和/或延长Bdq疗程方案的有效性。
我们模拟了一项目标试验，比较起始并维持核心方案与以下强化方案的有效性：1）Bdq治疗≥9个月，2）Bdq治疗≥9个月加德拉马尼（Dlm），3）亚胺培南（Imp），4）二线注射剂，或5）Bdq治疗≥9个月、Dlm和Imp。我们使用克隆、删失和逆概率加权来估计成功治疗的概率。
调整后的成功治疗概率范围为0.75（95%置信区间0.61 - 0.89）至0.84（95%置信区间0.76 - 0.91）。治疗成功率的比值范围为：用Bdq≥9个月（95%置信区间0.79 - 1.28）和Bdq≥9个月加Dlm（95%置信区间0.81 - 1.31）强化的方案为1.01，用注射剂（95%置信区间0.92 - 1.39）和Bdq≥9个月、Dlm和Imp（95%置信区间0.90 - 1.41）强化的方案为1.11。
一些强化方案的治疗成功率略高，但估计值不准确。需要对耐FQ个体中最大化治疗成功的策略进行更多研究。
