Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Clinical Trial Centre, Department of Dermatology, University of Zurich, Zurich, Switzerland.
Lancet Infect Dis. 2017 Mar;17(3):322-329. doi: 10.1016/S1473-3099(16)30529-1. Epub 2016 Dec 20.
Lyme borreliosis develops in 1-5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings.
In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39.
Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42-2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0·87), and most adverse events were mild.
Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks.
Ixodes AG.
在被蜱虫叮咬的人群中，约有 1%-5%会发展为莱姆病，但由于诊断存在空白，多达 30%的患者未得到确诊，因此我们需要一种广泛适用的药理学预防策略。在临床前研究中，局部使用阿奇霉素可有效清除伯氏疏螺旋体。我们评估了其在人体中的疗效。
在这项于德国和奥地利 28 个研究点进行的随机、双盲、安慰剂对照、多中心试验中，成年人被平均分配，在确诊被蜱虫叮咬后 72 小时内，连续 3 天每日两次接受局部使用 10%阿奇霉素或安慰剂治疗。通过一个互动语音应答系统，药剂师不参与研究，按研究点分层的随机号码在研究中心被接入。主要终点是在基线时血清阴性、研究期间没有发生其他蜱虫叮咬且在 8 周时有血清学结果的参与者中，治疗失败的数量，定义为游走性红斑、血清转换或两者兼有（意向治疗人群）。这项研究在 EudraCT 注册，编号 2011-000117-39。
在 2011 年 7 月 7 日至 2012 年 12 月 3 日期间，共有 1371 名参与者被随机分配接受治疗，其中 995 名被纳入意向治疗人群。由于接受阿奇霉素治疗的组中主要终点没有改善，该试验提前停止。在 8 周时，阿奇霉素组的 505 名参与者中有 11 名（2%）和安慰剂组的 490 名参与者中有 11 名（2%）治疗失败（比值比 0.97，95%CI 0.42-2.26，p=0.47）。局部阿奇霉素耐受性良好。两组出现不良反应的患者数量相似（阿奇霉素组 175 例[26%]，安慰剂组 177 例[26%]，p=0.87），大多数不良反应为轻度。
局部阿奇霉素耐受性良好，安全性良好。将无症状血清转换纳入主要疗效分析中，并没有显示局部阿奇霉素具有预防效果。应考虑进行适当的、仅评估游走性红斑的、有足够效力的研究。本研究的亚组分析表明，局部使用阿奇霉素可减少感染蜱虫叮咬后的游走性红斑。
Ixodes AG。
