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，患有严重疾病住院的儿童在出院后的发病率和死亡率都很高。这些儿童是可接触的高危人群，针对他们采取有针对性的干预措施，预防发病和死亡，可能会产生巨大影响。在撒哈拉以南非洲沙眼流行地区的大规模药物给药规划中进行的一项大型集群随机试验表明，在接受治疗的社区中，1-9岁儿童的死亡率降低了近50%。然而，阿奇霉素的大量用药导致治疗社区内大环内酯类药物耐药性的迅速出现，而且费用昂贵。在儿童出院时靶向给药阿奇霉素可能是一种新的和实用的干预措施，以最大限度地提高效益，同时最大限度地降低抗生素耐药性的风险。我们提出了一项随机、双盲、安慰剂对照试验，以确定与安慰剂相比，出院时提供阿奇霉素在降低肯尼亚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在这一人群中降低发病率和死亡率的潜在机制，并将评估在接受治疗的个体及其主要照顾者中出现的抗生素耐药性。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.