Sehgal Neha, Pajuelo Monica J, Gilman Robert H, Pickering Amy J, Earl Ashlee M, Worby Colin J, Nadimpalli Maya L
Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Laboratorio de Microbiología Molecular, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias e Ingeniería, Universidad Peruana Cayetano Heredia, Lima, Peru.
medRxiv. 2024 Dec 14:2024.12.13.24317790. doi: 10.1101/2024.12.13.24317790.
The effects of antibiotic use on children's gut microbiomes and resistomes are not well characterized in middle-income countries, where pediatric antibiotic consumption is exceptionally common. We characterized the effects of antibiotics commonly used by Peruvian children (i.e., amoxicillin, azithromycin, cefalexin, sulfa-trimethoprim) on gut diversity, genera, and antibiotic resistance gene (ARG) abundance from 3-16 months.
This study included 54 children from a prospective cohort of enteric infections in peri-urban Lima, 2016-2019. Stool collected at 3, 6, 7, 9, 12, and 16 months underwent DNA extraction and short-read metagenomic sequencing. We profiled the taxonomy of stool metagenomes and assessed ARG abundance by aligning reads to the ResFinder database. We used daily surveillance data (40,662 observations) to tabulate the number of antibiotic courses consumed in the 30 days prior to stool sampling. Using linear mixed models, the association of recent antibiotic use with species richness, diversity, gut genera, and ARG abundance over time was examined.
Most children were vaginally delivered (73%), received breastmilk almost daily over the study period, and belonged to socioeconomically diverse households. Amoxicillin, azithromycin, cefalexin, and sulfa-trimethoprim did not impact gut diversity or genera abundance. Azithromycin use significantly impacted ARGs from the macrolide, aminoglycoside, and folate pathway antagonist classes. Amoxicillin use significantly increased total ARGs. Antibiotics' effects on ARGs appeared to be independent of gut microbiome changes.
Common antibiotics like amoxicillin and azithromycin may be key drivers of the gut resistome but not the microbiome during early childhood in this setting with frequent breastfeeding.
在儿科抗生素消费异常普遍的中等收入国家，抗生素使用对儿童肠道微生物群和耐药基因组的影响尚未得到充分描述。我们描述了秘鲁儿童常用的抗生素（即阿莫西林、阿奇霉素、头孢氨苄、磺胺甲恶唑）对3至16个月儿童肠道多样性、属和抗生素抗性基因（ARG）丰度的影响。
本研究纳入了2016 - 2019年利马城郊肠道感染前瞻性队列中的54名儿童。在3、6、7、9、12和16个月时收集的粪便进行DNA提取和短读长宏基因组测序。我们对粪便宏基因组的分类学进行了分析，并通过将读数与ResFinder数据库比对来评估ARG丰度。我们使用每日监测数据（40662条观察记录）来统计粪便采样前30天内服用的抗生素疗程数。使用线性混合模型，研究了近期抗生素使用与物种丰富度、多样性、肠道属以及随时间变化的ARG丰度之间的关联。
大多数儿童通过阴道分娩（73%），在研究期间几乎每天都接受母乳喂养，并且来自社会经济背景多样的家庭。阿莫西林、阿奇霉素、头孢氨苄和磺胺甲恶唑对肠道多样性或属丰度没有影响。使用阿奇霉素显著影响了大环内酯类、氨基糖苷类和叶酸途径拮抗剂类的ARG。使用阿莫西林显著增加了总ARG。抗生素对ARG的影响似乎独立于肠道微生物群的变化。
在这种频繁母乳喂养的环境中，阿莫西林和阿奇霉素等常用抗生素可能是儿童早期肠道耐药基因组而非微生物群的关键驱动因素。
