Azithromycin to prevent post-discharge morbidity and mortality in Kenyan children

描述（由申请人提供）：在撒哈拉以南非洲，因严重疾病住院的儿童在出院后的发病率和死亡率风险较高。这些儿童是一个容易接触的高风险人群，预防发病率和死亡率的有针对性的干预措施可能会产生巨大的影响。在撒哈拉以南非洲沙眼流行地区的一项大规模药物管理计划中进行的一项大型阿奇霉素随机分组试验表明，在接受治疗的社区中，1-9岁儿童的死亡率几乎提高了50%。然而，阿奇霉素的大规模给药导致治疗社区内大环内酯类药物耐药性的迅速出现，并且价格昂贵。在出院时将阿奇霉素靶向输送给儿童可能是一种新颖实用的干预措施，可以最大限度地提高获益，同时最大限度地降低抗生素耐药性的风险。我们提出一项随机、双盲、安慰剂对照试验，以确定出院时提供阿奇霉素与安慰剂相比在降低肯尼亚1-59个月儿童死亡率和再住院率方面的疗效。该研究还将调查阿奇霉素可能降低该人群发病率和死亡率的潜在机制，并将评估治疗个体及其主要照顾者中抗生素耐药性的出现。还将对干预措施进行成本效益分析。

DESCRIPTION (provided by applicant): Children hospitalized with severe illness in sub-Saharan Africa are at high risk of morbidity and mortality following discharge from hospital. These children represent an accessible high-risk population in which targeted interventions to prevent morbidity and mortality could have dramatic impact. A large cluster randomized trial of azithromycin delivered in a mass drug administration program within trachoma endemic areas in sub-Saharan Africa demonstrated an almost 50% mortality benefit in children 1-9 years of age in treated communities. However, mass drug administration of azithromycin leads to the rapid emergence of macrolide resistance within treated communities and is expensive. The targeted delivery of azithromycin to children at hospital discharge may be a novel and practical intervention to maximize benefit while minimizing risk of antibiotic resistance. We propose a randomized, double-blind, placebo-controlled trial to determine the efficacy of azithromycin provided at discharge, compared to placebo, in reducing mortality and re-hospitalization rates in children age 1-59 months in Kenya. The study will also investigate potential mechanisms by which azithromycin may reduce morbidity and mortality in this population and will assess the emergence of antibiotic resistance among treated individuals and their primary caregivers. A cost-effectiveness analysis of the intervention will also be conducted.