Division of Physiology, Department of Medical Biochemistry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Antimicrob Agents Chemother. 2013 May;57(5):2199-203. doi: 10.1128/AAC.02243-12. Epub 2013 Mar 4.
Bedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10 CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P = 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P = 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies.
贝达喹啉是一种针对 ATP 合酶的新型抗结核药物。这项纳入了 68 例痰涂片阳性肺结核患者的随机、双盲研究评估了每日剂量为 100mg、200mg、300mg 和 400mg 的贝达喹啉的 14 天早期杀菌活性，这些剂量分别在第 1 天治疗时给予负荷剂量 200mg、400mg、500mg 和 700mg，以及在第 2 天治疗时给予负荷剂量 100mg、300mg、400mg 和 500mg。所有组均显示出活性，在 14 天内平均（标准差）log10CFU 每日下降分别为 0.040（0.068）、0.056（0.051）、0.077（0.064）和 0.104（0.077），在 100mg、200mg、300mg 和 400mg 组中。剂量的线性趋势具有统计学意义（P=0.001），并且 400mg 剂量组的活性大于 100mg 组（P=0.014）。所有贝达喹啉组均显示出显著的杀菌活性，这种活性持续到 14 天评估期结束。剂量呈线性趋势的发现表明，应考虑安全性因素，选择最高剂量进行更长期的临床研究。
