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标题：Frequency of bystander exposure to antibiotics for enteropathogenic bacteria among young children in low-resource settings
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作者：Elizabeth T. Rogawski McQuade ; Stephanie A. Brennhofer ; Sarah E. Elwood 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：36
DOI：10.1073/pnas.2208972119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance Antimicrobial resistance is a pressing concern, and while antibiotic stewardship interventions are intended to limit unnecessary antibiotic exposures, including to asymptomatically carried pathogens (i.e., bystander exposure), the frequency and characteristics of these bystander exposures have not been well described. We quantified the frequency that bacterial enteric pathogens were exposed to antibiotics when not the target of treatment in a study of children in low-resource settings. Our analysis demonstrated that almost all enteropathogen exposures to antibiotics occurred when the bacteria were carried asymptomatically, and respiratory infections were responsible for the largest proportion of exposures. Interventions to reduce antibiotic use and the illnesses that prompt treatment could have the ancillary benefit of reducing selection pressure for antimicrobial resistance among pathogens carried asymptomatically. Children in low-resource settings carry enteric pathogens asymptomatically and are frequently treated with antibiotics, resulting in opportunities for pathogens to be exposed to antibiotics when not the target of treatment (i.e., bystander exposure). We quantified the frequency of bystander antibiotic exposures for enteric pathogens and estimated associations with resistance among children in eight low-resource settings. We analyzed 15,697 antibiotic courses from 1,715 children aged 0 to 2 y from the MAL-ED birth cohort. We calculated the incidence of bystander exposures and attributed exposures to respiratory and diarrheal illnesses. We associated bystander exposure with phenotypic susceptibility of E. coli isolates in the 30 d following exposure and at the level of the study site. There were 744.1 subclinical pathogen exposures to antibiotics per 100 child-years. Enteroaggregative Escherichia coli was the most frequently exposed pathogen, with 229.6 exposures per 100 child-years. Almost all antibiotic exposures for Campylobacter (98.8%), enterotoxigenic E. coli (95.6%), and typical enteropathogenic E. coli (99.4%), and the majority for Shigella (77.6%), occurred when the pathogens were not the target of treatment. Respiratory infections accounted for half (49.9%) and diarrheal illnesses accounted for one-fourth (24.6%) of subclinical enteric bacteria exposures to antibiotics. Bystander exposure of E. coli to class-specific antibiotics was associated with the prevalence of phenotypic resistance at the community level. Antimicrobial stewardship and illness-prevention interventions among children in low-resource settings would have a large ancillary benefit of reducing bystander selection that may contribute to antimicrobial resistance.
关键词：enantimicrobial resistanceantibioticsbystander exposureenteric infectionschildren