Department of Pharmacology, B. J. Medical College & Civil Hospital, Ahmedabad, 380016, India.
Department of Pharmacology, B. J. Medical College & Civil Hospital, Ahmedabad, 380016, India.
Indian J Tuberc. 2020 Apr;67(2):222-230. doi: 10.1016/j.ijtb.2020.03.002. Epub 2020 Mar 24.
Bedaquiline (BDQ) has been recently approved for drug resistant tuberculosis with active drug safety monitoring under programmatic condition. The present study was conducted to evaluate safety, tolerability and efficacy of bedaquiline plus optimised background regimen.
A prospective study was conducted on cohort of pre-extensively drug resistant (XDR) and XDR pulmonary TB patients. Eligible patients were closely monitored for cardiac safety, adverse events (AEs), clinical and microbiological improvement during BDQ (6 months) and post BDQ phase for twelve months.
Of 127 patients enrolled, a significant increase in mean QTc interval was observed on 13th day and 3rd week as compared to baseline (p < 0.0001). Mean maximum increase of QTc was 37.92ms (95% CI, 14.1-61.74ms). Concomitant anti-TB medications, age, gender, low body mass index (BMI) had significant effect on QTc prolongation (p < 0.0001, p < 0.05). However, none of the patient required discontinuation of BDQ. Majority of AEs (86.3%) were non-serious and not preventable 108 (87.1%). The median time for sputum-culture conversion was 40.89 ± 3.5 days (95% CI, 34-48 days) and the treatment outcome was successful in 102 (80.3%) patients with negative sputum culture conversion.
Bedaquiline containing regimen achieved favourable outcome. Although, bedaquiline along with concomitant anti-TB medications has the potential to prolong QTc interval, the benefit certainly outweighs the risk. This calls for a through pre-treatment cardiovascular and biochemical evaluation as a preventive measure and appropriate selection of patients for safe use of BDQ and successful outcome.
贝达喹啉（BDQ）最近已在计划条件下获得耐药结核病的药物安全监测批准。本研究旨在评估贝达喹啉联合优化背景方案的安全性、耐受性和疗效。
对一组预广泛耐药（XDR）和 XDR 肺结核患者进行前瞻性研究。密切监测合格患者的心脏安全性、不良反应（AE）、BDQ（6 个月）期间的临床和微生物学改善以及 BDQ 后 12 个月的情况。
在 127 名入组患者中，与基线相比，第 13 天和第 3 周观察到平均 QTc 间隔明显增加（p<0.0001）。平均最大 QTc 增加 37.92ms（95%CI，14.1-61.74ms）。同时使用抗结核药物、年龄、性别、低体重指数（BMI）对 QTc 延长有显著影响（p<0.0001，p<0.05）。然而，没有患者需要停止使用 BDQ。大多数不良反应（86.3%）是非严重且不可预防的，共 108 例（87.1%）。痰培养转阴的中位时间为 40.89±3.5 天（95%CI，34-48 天），102 例（80.3%）患者痰培养转阴，治疗结果成功。
含贝达喹啉的方案取得了良好的结果。虽然贝达喹啉与同时使用的抗结核药物有延长 QTc 间隔的潜力，但益处肯定大于风险。这需要在治疗前进行全面的心血管和生化评估，作为预防措施，并适当选择患者安全使用 BDQ 并取得成功。
