抗生素选择压力对鼻咽大环内酯类耐药组的影响：一项集群随机试验。

The Effect of Antibiotic Selection Pressure on the Nasopharyngeal Macrolide Resistome: A Cluster-randomized Trial.

机构信息

Francis I. Proctor Foundation, University of California, San Francisco.

Department of Ophthalmology, University of California, San Francisco.

出版信息

Clin Infect Dis. 2018 Nov 13;67(11):1736-1742. doi: 10.1093/cid/ciy339.

DOI:10.1093/cid/ciy339

PMID:29897440

Abstract

BACKGROUND

Frequent use of antibiotics is thought to create selection pressure by clearing susceptible bacteria and allowing resistant bacteria to spread in a community. A cluster-randomized trial comparing 2 different frequencies of mass azithromycin distributions for trachoma provided a convenient experiment for determining the causal relationship between antibiotic consumption and antibiotic resistance.

METHODS

Twenty-four communities were randomized to either annual or biannual mass azithromycin distributions for trachoma. Randomization was stratified on health catchment area and trachoma prevalence. Swabs were processed for the genetic macrolide resistance determinants ermB and mefA/E in a masked fashion from a random sample of 120 preschool children before treatment and another 120 children after 2 years of mass antibiotics.

RESULTS

Macrolide resistance determinants were similar in the 12 annually and 12 biannually treated communities before treatment, with a median prevalence among preschool children of 20% (interquartile range [IQR], 10%-40%) in each group. By 24 months, macrolide resistance determinants were found more commonly in the biannually treated communities (median, 60% [IQR, 50%-80%]) than the annually treated communities (median, 40% [IQR, 20%-40%]; P < .001). Adjusting for baseline, the 24-month prevalence of macrolide resistance determinants in the biannual group was 29.4% higher than that of the annual group (95% confidence interval, 10.5%-56.7%).

CONCLUSIONS

This randomized trial used direct genetic methods to confirm the causal relationship of community antibiotic consumption and antibiotic resistance. Communities randomized to less frequent use of antibiotics had a significantly lower prevalence of genetic antibiotic resistance determinants.

CLINICAL TRIALS REGISTRATION

NCT00792922.

摘要

背景

人们认为频繁使用抗生素会通过清除敏感菌并使耐药菌在社区中传播，从而产生选择压力。一项比较两种不同频率的大规模阿奇霉素治疗沙眼的随机对照试验为确定抗生素消耗与抗生素耐药性之间的因果关系提供了一个方便的实验。

方法

24 个社区被随机分为每年或每两年进行一次大规模阿奇霉素治疗沙眼。随机化按照卫生集水区和沙眼流行率进行分层。在治疗前，从每个社区的 120 名学龄前儿童中随机抽取 120 名进行盲法处理，以获得 ermB 和 mefA/E 基因大环内酯类耐药决定因素的拭子，并在 2 年后对另 120 名儿童进行处理。

结果

在治疗前，每年治疗的 12 个社区和每两年治疗的 12 个社区的大环内酯类耐药决定因素相似，每组学龄前儿童的中位数患病率为 20%（四分位间距[IQR]，10%-40%）。24 个月时，在每两年治疗的社区中更常见发现大环内酯类耐药决定因素（中位数，60%[IQR，50%-80%]），而每年治疗的社区中则较常见（中位数，40%[IQR，20%-40%]；P<0.001）。调整基线后，每两年治疗组的大环内酯类耐药决定因素 24 个月的患病率比每年治疗组高 29.4%（95%置信区间，10.5%-56.7%）。