水、环境卫生、个人卫生和营养干预措施减少幼儿抗生素使用的途径：一项嵌套于整群随机试验中的队列研究的中介分析

Pathways through which water, sanitation, hygiene, and nutrition interventions reduce antibiotic use in young children: a mediation analysis of a cohort nested within a cluster-randomized trial.

作者信息

Nguyen Anna T, Heitmann Gabby Barratt, Mertens Andrew, Ashraf Sania, Rahman Md Ziaur, Ali Shahjahan, Rahman Mahbub, Arnold Benjamin F, Grembi Jessica A, Lin Audrie, Ercumen Ayse, Benjamin-Chung Jade

机构信息

Department of Epidemiology and Population Health, School of Medicine, Stanford University, Stanford, CA, USA.

Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.

出版信息

EClinicalMedicine. 2025 Mar 6;82:103147. doi: 10.1016/j.eclinm.2025.103147. eCollection 2025 Apr.

DOI:10.1016/j.eclinm.2025.103147

PMID:40123738

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11928822/

Abstract

BACKGROUND

Low-cost, household-level water, sanitation, and hygiene (WASH) and nutrition interventions can reduce pediatric antibiotic use, but the mechanism through which interventions reduce antibiotic use has not been investigated.

METHODS

We conducted a causal mediation analysis using data collected between September 2013 and October 2015 from a cohort nested within the WASH Benefits Bangladesh cluster-randomized trial (NCT01590095). Among a subsample of children within the WASH, nutrition, nutrition + WASH, and control arms (N = 1409 children; 267 clusters), we recorded caregiver-reported antibiotic use at ages 14 and 28 months and collected stool at age 14 months. Our primary outcome was any caregiver-reported antibiotic use by index children within the past 30 or 90 days measured at age 14 and 28 months. Mediators included caregiver-reported child diarrhea, acute respiratory infection (ARI), and fever; and enteric pathogen carriage in stool measured by qPCR. Both intervention-mediator and mediator-outcome models were controlled for mediator-outcome confounders.

FINDINGS

The receipt of any WASH or nutrition intervention reduced caregiver-reported antibiotic use through all pathways in the past month by 5.5 percentage points (95% CI 1.2, 9.9), from 49.5% (95% CI 45.9%, 53.0%) in the control group to 45.0% (95% CI 42.7%, 47.2%) in the pooled intervention group. When separating this effect into different pathways, we found that interventions reduced antibiotic use by 0.6 percentage points (95% CI 0.1, 1.3) through reduced diarrhea, 0.7 percentage points (95% CI 0.1, 1.5) through reduced ARI with fever, and 1.5 percentage points (95% CI 0.4, 3.0) through reduced prevalence of enteric viruses. Interventions reduced antibiotic use through any of these measured mediators by 2.1 percentage points (95% CI -0.3, 4.5).

INTERPRETATION

WASH and nutrition interventions reduced pediatric antibiotic use through the prevention of enteric and respiratory infections in a rural, low-income population. Given that many of these infections are caused by viruses or parasites, WASH and nutrition interventions may help reduce inappropriate antibiotic use in similar settings.

FUNDING

Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases.

摘要

背景

低成本的家庭层面的水、环境卫生和个人卫生（WASH）及营养干预措施可减少儿科抗生素的使用，但干预措施减少抗生素使用的机制尚未得到研究。

方法

我们利用2013年9月至2015年10月期间从孟加拉国WASH福利整群随机试验（NCT01590095）中的一个队列收集的数据进行了因果中介分析。在WASH、营养、营养+WASH和对照组的儿童子样本中（N = 1409名儿童；267个群组），我们记录了照护者报告的14个月和28个月大时儿童使用抗生素的情况，并在14个月大时收集了粪便。我们的主要结局是在14个月和28个月时测量的索引儿童在过去30天或90天内照护者报告的任何抗生素使用情况。中介变量包括照护者报告的儿童腹泻、急性呼吸道感染（ARI）和发烧；以及通过定量聚合酶链反应（qPCR）测量的粪便中肠道病原体携带情况。干预-中介变量模型和中介变量-结局模型均对中介变量-结局混杂因素进行了控制。

结果

接受任何WASH或营养干预措施通过所有途径使过去一个月照护者报告的抗生素使用减少了5.5个百分点（95%置信区间1.2，9.9），从对照组的49.5%（95%置信区间45.9%，53.0%）降至合并干预组的45.0%（95%置信区间42.7%，47.2%）。当将这种效应分为不同途径时，我们发现干预措施通过减少腹泻使抗生素使用减少了0.6个百分点（95%置信区间0.1，1.3），通过减少伴有发烧的ARI使抗生素使用减少了0.7个百分点（95%置信区间0.1，1.5），通过降低肠道病毒流行率使抗生素使用减少了1.5个百分点（95%置信区间0.4，3.0）。干预措施通过这些测量的中介变量中的任何一个使抗生素使用减少了2.1个百分点（95%置信区间-0.3，4.5）。