Substitution of Moxifloxacin for Isoniazid during Intensive Phase Treatment of Pulmonary Tuberculosis
Substitution of Moxifloxacin for Isoniazid during Intensive Phase Treatment of Pulmonary Tuberculosis
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DOI：
10.1164/rccm.200901-0078oc
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发表时间：
2009-08-01
影响因子：
24.7
通讯作者：
Chaisson, Richard E.
中科院分区：
文献类型：
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作者：
Dorman, Susan E.;Johnson, John L.;Chaisson, Richard E.
基本原理 莫西沙星在体外和抗结核 (TB) 化疗小鼠模型中具有有效的抗结核分枝杆菌活性，但有关其在人体中活性的数据有限。目的：我们的目的是比较莫西沙星与异烟肼在肺结核联合治疗的前 8 周内的抗菌活性和安全性。方法：痰涂片阳性肺结核成人患者被随机分配接受莫西沙星 400 mg 加异烟肼安慰剂，或异烟肼 300 环加莫西沙星安慰剂，每周 5 天，持续 8 周，此外还接受利福平，吡嗪酰胺和乙胺丁醇。直接观察所有剂量。每2周收集痰液进行培养。主要结果是 8 周治疗完成后痰培养呈阴性。测量和主要结果：在 433 名参与者中，328 名符合主要疗效分析的条件。其中，35 例 (11%) 呈 HIV 阳性，248 例 (76%) 基线胸部 X 光片显示有空洞，213 例 (65%) 在非洲站点登记。第 8 周时，异烟肼组 90/164 (54.9%) 参与者和莫西沙星组 99/164 (60.4%) 参与者观察到培养阴性 (P = 0.37)。在多变量分析中，非洲地点的空化和入组与第 8 周培养阴性的可能性较低相关。莫西沙星组停止指定治疗的参与者比例为 31/214 (14.5%)，而异烟肼组则为 22/205 (10.7%)（RR，1.35；95% CI，0.81，2.25）。 结论：用莫西沙星替代异烟肼导致第 8 周培养值出现小幅但无统计学意义的增加消极情绪。
Rationale Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited. Objectives: Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB.Methods: Adults with sputum smear-positive pulmonary TB were randomly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo, or isoniazid 300 ring plus moxifloxacin placebo, administered 5 days/week for 8 weeks, in addition to rifampin, pyrazinamide, and ethambutol. All doses were directly observed. Sputum was collected for culture every 2 weeks. The primary outcome was negative sputum culture at completion of 8 weeks of treatment.Measurements and Main Results: Of 433 participants enrolled, 328 were eligible for the primary efficacy analysis. Of these, 35 (11%) were HIV positive, 248 (76%) had cavitation on baseline chest radiograph, and 213 (65%) were enrolled at African sites. Negative Cultures at Week 8 were observed in 90/164 (54.9%) participants in the isoniazid arm, and 99/164 (60.4%) in the moxifloxacin arm (P = 0.37). In multivariate analysis, cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity. The proportion of participants who discontinued assigned treatment was 31/214 (14.5%) for the moxifloxacin group versus 22/205 (10.7%) for the isoniazid group (RR, 1.35; 95% CI, 0.81, 2.25).Conclusions: Substitution of moxifloxacin for isoniazid resulted in a small but statistically nonsignificant increase in Week-8 culture negativity.