BACKGROUND Acute diarrhoea is a common cause of illness and death among children in low- to middle-income settings. World Health Organization guidelines for the clinical management of acute watery diarrhoea in children focus on oral rehydration, supplemental zinc and feeding advice. Routine use of antibiotics is not recommended except when diarrhoea is bloody or cholera is suspected. Young children who are undernourished or have a dehydrating diarrhoea are more susceptible to death at 90 days after onset of diarrhoea. Given the mortality risk associated with diarrhoea in children with malnutrition or dehydrating diarrhoea, expanding the use of antibiotics for this subset of children could be an important intervention to reduce diarrhoea-associated mortality and morbidity. We designed the Antibiotics for Childhood Diarrhoea (ABCD) trial to test this intervention. METHODS ABCD is a double-blind, randomised trial recruiting 11,500 children aged 2-23 months presenting with acute non-bloody diarrhoea who are dehydrated and/or undernourished (i.e. have a high risk for mortality). Enrolled children in Bangladesh, India, Kenya, Malawi, Mali, Pakistan and Tanzania are randomised (1:1) to oral azithromycin 10 mg/kg or placebo once daily for 3 days and followed-up for 180 days. Primary efficacy endpoints are all-cause mortality during the 180 days post-enrolment and change in linear growth 90 days post-enrolment. DISCUSSION Expanding the treatment of acute watery diarrhoea in high-risk children to include an antibiotic may offer an opportunity to reduce deaths. These benefits may result from direct antimicrobial effects on pathogens or other incompletely understood mechanisms including improved nutrition, alterations in immune responsiveness or improved enteric function. The expansion of indications for antibiotic use raises concerns about the emergence of antimicrobial resistance both within treated children and the communities in which they live. ABCD will monitor antimicrobial resistance. The ABCD trial has important policy implications. If the trial shows significant benefits of azithromycin use, this may provide evidence to support reconsideration of antibiotic indications in the present World Health Organization diarrhoea management guidelines. Conversely, if there is no evidence of benefit, these results will support the current avoidance of antibiotics except in dysentery or cholera, thereby avoiding inappropriate use of antibiotics and reaffirming the current guidelines. TRIAL REGISTRATION Clinicaltrials.gov, NCT03130114. Registered on April 26 2017.

中文翻译：

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在资源匮乏的环境中，阿奇霉素的双盲安慰剂对照试验可降低死亡率和改善非血性腹泻的高危幼儿的生长：腹泻儿童抗生素（ABCD）试验方案。

背景技术急性腹泻是中低收入儿童中疾病和死亡的常见原因。世界卫生组织儿童急性水样腹泻的临床管理指南侧重于口服补液，补充锌和喂养建议。不建议常规使用抗生素，除非腹泻是血腥的或怀疑是霍乱。营养不良或脱水腹泻的幼儿在腹泻发作后90天更容易死亡。鉴于营养不良或脱水腹泻的儿童有腹泻的死亡风险，因此扩大对这一部分儿童抗生素的使用可能是减少腹泻相关死亡率和发病率的重要干预措施。我们设计了用于儿童腹泻的抗生素（ABCD）试验来测试该干预措施。方法ABCD是一项双盲，随机试验，招募了11,500名2-23个月大的儿童，他们患有脱水和/或营养不良（即高死亡风险）的急性非血性腹泻。将孟加拉国，印度，肯尼亚，马拉维，马里，巴基斯坦和坦桑尼亚的入学儿童随机（1：1）口服阿奇霉素10 mg / kg或安慰剂，每天一次，连续3天，随后进行180天。主要功效终点是入院后180天内的全因死亡率和入院90天后的线性增长变化。讨论将高危儿童的急性水样腹泻治疗扩大到包括抗生素在内，可能会提供减少死亡的机会。这些益处可能来自对病原体的直接抗菌作用或其他未完全理解的机制，包括改善的营养，免疫应答的改变或改善的肠功能。抗生素使用适应症的扩大引起了人们对在治疗的儿童及其居住社区中出现抗菌素耐药性的担忧。ABCD将监测抗菌素耐药性。ABCD试验具有重要的政策含义。如果试验显示出使用阿奇霉素的显着益处，则可能为支持重新考虑目前世界卫生组织腹泻管理指南中的抗生素适应症提供证据。相反，如果没有证据表明有益处，这些结果将支持目前避免使用抗生素，除非是痢疾或霍乱，从而避免了抗生素的不当使用，并重申了当前的指南。试验注册Clinicaltrials.gov，NCT03130114。2017年4月26日注册。