Effect of Long-term, Low-Dose Erythromycin on Pulmonary Exacerbations Among Patients With Non-Cystic Fibrosis Bronchiectasis The BLESS Randomized Controlled Trial
Effect of Long-term, Low-Dose Erythromycin on Pulmonary Exacerbations Among Patients With Non-Cystic Fibrosis Bronchiectasis The BLESS Randomized Controlled Trial
复制标题
DOI：
10.1001/jama.2013.2290
复制
发表时间：
2013-03-27
影响因子：
120.7
通讯作者：
Bowler, Simon D.
中科院分区：
文献类型：
--
作者：
Serisier, David J.;Martin, Megan L.;Bowler, Simon D.
重要性大环内酯类抗生素如红霉素可改善非囊性纤维化（CF）支气管扩张的临床结局，尽管大环内酯类耐药的相关风险定义不清。目的评价对有频繁肺加重病史的非CF支气管扩张患者给予低剂量红霉素12个月的临床疗效和抗菌药物耐药性成本。一项随机（1：1）、双盲、安慰剂对照试验，在当前不吸烟、前一年有2次或2次以上感染加重史的非CF支气管扩张成人患者中评价红霉素。这项澳大利亚研究于2008年10月至2011年12月在一所大学教学医院进行，参与者也通过其他中心的呼吸内科医生和公共广播广告招募。干预措施每日两次琥乙红霉素（400 mg）或匹配安慰剂。主要结果测量主要结果是每例患者的方案定义的肺加重（PDPEs）的年平均率。次要结果包括大环内酯类药物耐药的口腔口咽链球菌和肺function.Results六百七十九例患者进行了筛选，117例随机（58安慰剂，59红霉素），107（91.5%）完成了研究。总的来说，红霉素显著降低了PDPE（平均值，1.29[95%CI，0.93-1.65] vs 1.97[95%CI，1.45-2.48]/例患者/年;发生率比[IRR]，0.57 [95%CI，0.42-0.77]; P=. 001）。003），而在预先指定的基线铜绿假单胞菌气道感染亚组中（平均差异，1. 32 [95% CI，0. 19 - 2. 46]; P=. 02）。红霉素可减少24小时痰量（中位差异为4.3 g [四分位距[IQR]，1 - 7.8]，P=. 01)与安慰剂组相比，肺功能下降减轻（呼气第一秒内支气管扩张剂后用力呼气量变化的平均绝对差异，2.2%预测值[95% CI，0.1%至4.3%]; P= 0.04）。红霉素增加了大环内酯类耐药口咽链球菌的比例（中位数变化，27.7% [IQR，0.04%至41.1%] vs 0.04% [IQR，-1.6%至1.5%];差异，25.5% [IQR，15.0%至33.7%]; P
Importance Macrolide antibiotics such as erythromycin may improve clinical outcomes in non-cystic fibrosis (CF) bronchiectasis, although associated risks of macrolide resistance are poorly defined.Objective To evaluate the clinical efficacy and antimicrobial resistance cost of low-dose erythromycin given for 12 months to patients with non-CF bronchiectasis with a history of frequent pulmonary exacerbations.Design, Setting, and Participants Twelve-month, randomized (1: 1), double-blind, placebo-controlled trial of erythromycin in currently nonsmoking, adult patients with non-CF bronchiectasis with a history of 2 or more infective exacerbations in the preceding year. This Australian study was undertaken between October 2008 and December 2011 in a university teaching hospital, with participants also recruited via respiratory physicians at other centers and from public radio advertisements.Interventions Twice-daily erythromycin ethylsuccinate (400mg) or matching placebo.Main Outcome Measures The primary outcome was the annualized mean rate of protocol-defined pulmonary exacerbations (PDPEs) per patient. Secondary outcomes included macrolide resistance in commensal oropharyngeal streptococci and lung function.Results Six-hundred seventy-nine patients were screened, 117 were randomized (58 placebo, 59 erythromycin), and 107 (91.5%) completed the study. Erythromycin significantly reduced PDPEs both overall (mean, 1.29[95% CI, 0.93-1.65] vs 1.97[95% CI, 1.45-2.48] per patient per year; incidence rate ratio [IRR], 0.57 [95% CI, 0.42-0.77]; P=. 003), and in the prespecified subgroup with baseline Pseudomonas aeruginosa airway infection (mean difference, 1.32[95% CI, 0.19-2.46]; P=. 02). Erythromycin reduced 24-hour sputum production (median difference, 4.3 g [interquartile range [IQR], 1 to 7.8], P=. 01) and attenuated lung function decline(mean absolute difference for change in postbronchodilator forced expiratory volume in the first second of expiration, 2.2 percent predicted [95% CI, 0.1% to 4.3%]; P=.04) compared with placebo. Erythromycin increased the proportion of macrolide-resistant oropharyngeal streptococci (median change, 27.7% [IQR, 0.04% to 41.1%] vs 0.04% [IQR, -1.6% to 1.5%]; difference, 25.5% [IQR, 15.0% to 33.7%]; P