Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam.

IF 96.2 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Greg J Fox, Nguyen Viet Nhung, Nguyen Cam Binh, Nguyen Binh Hoa, Frances L Garden, Andrea Benedetti, Pham Ngoc Yen, Nguyen Kim Cuong, Emily L MacLean, H Manisha Yapa, David W Dowdy, Nguyen Huu Lan, Elyse Guevara-Rattray, Pham Duc Cuong, Ori Solomon, Marcel A Behr, Ben J Marais, Steven M Graham, Dick Menzies, Nguyen Thu Anh, Guy B Marks
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引用次数: 0

Abstract

Background: Prevention of drug-resistant tuberculosis is a global health priority. However, trials evaluating the effectiveness of treating Mycobacterium tuberculosis infection among contacts of persons with drug-resistant tuberculosis are lacking.

Methods: We conducted a double-blind, randomized, controlled trial comparing 6 months of daily levofloxacin (weight-based doses) with placebo to treat M. tuberculosis infection. The trial population comprised household contacts of persons with bacteriologically confirmed rifampicin-resistant or multidrug-resistant (MDR) tuberculosis in Vietnam. Contacts of any age with a positive tuberculin skin test or immunologic impairment were eligible. The primary end point was bacteriologically confirmed tuberculosis within 30 months. Secondary end points included grade 3 or 4 adverse events, death from any cause, and acquired drug resistance.

Results: Of 3948 persons screened for eligibility, 61 (1.5%) had coprevalent tuberculosis (defined as active tuberculosis disease diagnosed before randomization) and 2041 underwent randomization. Of these 2041 participants, 1995 (97.7%) completed 30 months of follow-up, had a primary end-point event, or died. Confirmed tuberculosis occurred in 6 participants (0.6%) in the levofloxacin group and 11 (1.1%) in the placebo group (incidence rate ratio, 0.55; 95% confidence interval [CI], 0.19 to 1.62); this difference was not significant. There was little difference in grade 3 or 4 adverse events between the two groups (risk difference, 1.0 percentage point; 95% CI, -0.3 to 2.4). Adverse events of any grade were reported in 306 participants (31.9%) taking levofloxacin and 125 (13.0%) taking placebo (risk difference, 18.9 percentage points; 95% CI, 14.2 to 23.6). No acquired fluoroquinolone resistance was observed.

Conclusions: Although the incidence of tuberculosis was lower in the levofloxacin group than in the placebo group at 30 months, the difference was not significant. (Funded by the National Health and Medical Research Council of Australia; VQUIN MDR Australia New Zealand Clinical Trials Registry number, ACTRN12616000215426.).

左氧氟沙星在越南预防耐多药结核病。
背景:预防耐药结核病是一项全球卫生优先事项。然而,缺乏评估在耐药结核病患者接触者中治疗结核分枝杆菌感染有效性的试验。方法:我们进行了一项双盲、随机、对照试验,比较6个月每日左氧氟沙星(以体重为基础剂量)与安慰剂治疗结核分枝杆菌感染的疗效。试验人群包括越南细菌学证实的利福平耐药或耐多药结核病患者的家庭接触者。结核菌素皮肤试验阳性或免疫缺陷的任何年龄的接触者都是合格的。主要终点是30个月内细菌学证实的结核病。次要终点包括3级或4级不良事件、任何原因导致的死亡和获得性耐药。结果:在筛选的3948人中,61人(1.5%)患有共价结核(定义为随机化前诊断的活动性结核病),2041人接受了随机化。在这2041名参与者中,1995名(97.7%)完成了30个月的随访,发生了主要终点事件或死亡。左氧氟沙星组确诊结核病患者6人(0.6%),安慰剂组确诊结核病患者11人(1.1%)(发病率比0.55;95%可信区间[CI], 0.19 ~ 1.62);这一差异并不显著。两组3级或4级不良事件发生率差异不大(风险差异1.0个百分点;95% CI, -0.3 ~ 2.4)。服用左氧氟沙星的306名参与者(31.9%)和服用安慰剂的125名参与者(13.0%)报告了任何级别的不良事件(风险差异为18.9个百分点;95% CI, 14.2 ~ 23.6)。未见获得性氟喹诺酮类药物耐药。结论:虽然30个月时左氧氟沙星组结核发病率低于安慰剂组,但差异不显著。(由澳大利亚国家卫生和医学研究委员会资助;VQUIN MDR澳大利亚新西兰临床试验注册号,ACTRN12616000215426)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
New England Journal of Medicine
New England Journal of Medicine 医学-医学:内科
CiteScore
145.40
自引率
0.60%
发文量
1839
审稿时长
1 months
期刊介绍: The New England Journal of Medicine (NEJM) stands as the foremost medical journal and website worldwide. With an impressive history spanning over two centuries, NEJM boasts a consistent publication of superb, peer-reviewed research and engaging clinical content. Our primary objective revolves around delivering high-caliber information and findings at the juncture of biomedical science and clinical practice. We strive to present this knowledge in formats that are not only comprehensible but also hold practical value, effectively influencing healthcare practices and ultimately enhancing patient outcomes.
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