Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial.
Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial.
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DOI：
10.1001/jama.2015.13896
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发表时间：
2015-11-17
期刊：
影响因子：
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通讯作者：
Martinez FD
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作者：
Bacharier LB;Guilbert TW;Mauger DT;Boehmer S;Beigelman A;Fitzpatrick AM;Jackson DJ;Baxi SN;Benson M;Burnham CD;Cabana M;Castro M;Chmiel JF;Covar R;Daines M;Gaffin JM;Gentile DA;Holguin F;Israel E;Kelly HW;Lazarus SC;Lemanske RF Jr;Ly N;Meade K;Morgan W;Moy J;Olin T;Peters SP;Phipatanakul W;Pongracic JA;Raissy HH;Ross K;Sheehan WJ;Sorkness C;Szefler SJ;Teague WG;Thyne S;Martinez FD
许多学龄前儿童会出现反复发作的严重下呼吸道疾病（LRTI）。虽然病毒感染经常存在，但细菌也可能有助于疾病的发病机制。需要采取有效缓解此类事件的战略。评估在重度LRTI症状发作前早期给予阿奇霉素治疗学龄前复发性重度LRTI儿童是否可以预防这些事件的进展。一项随机、双盲、安慰剂对照、平行组试验，在美国国家心脏、肺和血液研究所AsthmaNet网络的9个美国学术医学中心进行，2011年4月开始招募，2014年12月完成随访。参与者是607名年龄在12到71个月之间的儿童，他们有复发性、严重的LRTI和最小的日常损害史。参与者被随机分配接受阿奇霉素（12 mg/kg/d，持续5天; n = 307）或匹配的安慰剂（n = 300），在每个预定义的RTI（LRTI发生前儿童的体征或症状）早期开始，基于个性化的行动计划，在12至18个月的时间内。主要结局指标为未进展为重度LRTI的RTI数量，在RTI水平测量，在临床实践中会触发口服皮质类固醇处方。口咽部样本中阿奇霉素耐药微生物的存在，沿着不良事件，是次要结局指标。443名儿童（阿奇霉素组，223名;安慰剂组，220名）共经历了937例治疗性RTI（阿奇霉素组，473名;安慰剂组，464名），包括92例重度LRTI（阿奇霉素组，35名;安慰剂组，57名）。与安慰剂相比，阿奇霉素显著降低了进展为重度LRTI的风险（风险比，0.64 [95%CI，0.41-0.98]，P = 0.04;首次RTI的绝对风险：阿奇霉素为0.05，安慰剂为0.08;风险差异为0.03 [95%CI，0.00-0.06]）。很少观察到阿奇霉素耐药微生物的诱导和不良事件。在有复发性严重下呼吸道感染病史的幼儿中，与安慰剂相比，在明显的呼吸道感染早期使用阿奇霉素降低了严重下呼吸道感染的可能性。需要更多的信息，对发展的抗药性病原体与这一战略。
Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child’s signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12-through 18-month period. The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed. Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy.