C Zeng, M A Hernán, L Trevisi, S Sauer, C D Mitnick, C Hewison, M Bastard, P Khan, K J Seung, M L Rich, S Law, M Kikvidze, O Kirakosyan, A Miankou, P Thit, S Mamsa, A Janmohamed, N Melikyan, S Ahmed, D Vargas, A B Binegdie, K Temirova, L Oyewusi, K Philippe, S C Vilbrun, U Khan, H Huerga, M F Franke
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引用次数: 0
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.
背景：多药/利福平耐药结核病（MDR/RR-TB）伴氟喹诺酮（FQ）耐药患者的治疗结果可能会受到影响。在FQ不太可能有效的人群中，我们比较了由贝达喹啉（Bdq） 5-8个月、利奈唑胺和氯法齐明组成的较长个性化方案与至少1种C组药物和/或较长Bdq持续时间的强化方案的有效性。方法：我们模拟了一项目标试验，比较开始和保持核心方案的有效性与1)Bdq≥9个月，2)Bdq≥9个月，以及delamanid （Dlm), 3)亚胺培南（Imp）， 4）二线注射剂，或5)Bdq≥9个月，Dlm和Imp的方案。我们使用克隆，审查和逆概率加权来估计成功治疗的概率。结果：治疗成功的调整概率范围为0.75 （95% CI 0.61-0.89）至0.84 （95% CI 0.76-0.91）。治疗成功率的比值范围从Bdq≥9个月（95% CI 0.79-1.28）和Bdq≥9个月加Dlm （95% CI 0.81-1.31）强化方案的1.01到注射强化方案的1.11 （95% CI 0.92-1.39）和Bdq≥9个月、Dlm和Imp （95% CI 0.90-1.41）。结论：一些强化方案的治疗成功率略高，但估计不准确。需要进一步研究在FQ耐药个体中使治疗成功率最大化的策略。
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