目的 探究产时抗菌药物预防(IAP)对6月龄内婴儿肠道菌群抗生素耐药基因(ARGs)的影响及纵向变化,为抗生素的规范性使用和耐药性控制提供理论依据。方法 基于母婴队列2018年1月—2019年6月数据,采集新生儿3日龄内、2月龄及6月龄粪便,使用qPCR技术检测6种常见ARGs(aac(6')-Ib、qnrS、blaTEM、ermB、mecA、tetM),计算ARGs丰度及阳性检出例数。采用非参数检验及线性混合效应模型(LMM)分析IAP在3个时间点对ARGs绝对丰度的影响,以及ARGs丰度在3个时间点的纵向变化。结果 共65名单胎婴儿的157个样本纳入分析,其中15名母亲(23.1%)接受了IAP。婴幼儿在出生后半年内ARGs检出率较高,丰度随时间呈增加趋势。IAP可显著增加经阴道分娩婴儿肠道菌群6月龄时mecA基因丰度(VDIAP组6.1±1.1 vs. VDno-IAP组 3.8±4.6, P=0.046),剖宫产婴儿的aac(6')-Ib 基因丰度则在2月龄(β=3.81,Sx-=1.45,P<0.05)、6月龄(β=4.89,Sx-=1.11,P<0.001)较3日龄有显著升高。结论 IAP可增加6月龄婴儿ARGs丰度,调整分娩方式影响后,该效应依然显著,提示合理规范使用产时抗菌药物可能减少抗生素耐药的形成。
Abstract
Objective To explore the impact of intrapartum antibiotic prophylaxis (IAP) on antibiotic resistance genes (ARGs) in the gut microbiota of infants up to 6 months of age and their longitudinal changes, in order to provide theoretical basis for the rational use of antibiotics and antibiotic resistance control. Methods Fecal samples were collected within 3 days, 2 months, and 6 months from a maternal and birth cohort conducted between January 2018 and June 2019. A panel of 6 common ARGs (aac(6')-Ib, qnrS, blaTEM, ermB, mecA, tetM) were tested, the absolute abundance and positive detection rate by qPCR were calculated. Nonparametric and linear mixed model (LMM) analysis were used to assess the influence of IAP on the absolute abundance of antibiotic resistance genes and the longitudinal changes in their abundance at the three time points. Results A total of 157 samples from 65 singleton infants were analyzed, including 15 mothers (23.1%) who received IAP. The detection rate of ARGs was high in infants up to six months of age, and the abundance of ARGs tended to increase over time. IAP significantly increased the abundance of the mecA gene in the gut microbiota of vaginally delivered infants at 6 months of age (6.1±1.1 in the VDIAP group vs. 3.8±4.6 in the VDno-IAP group, P=0.046). Additionally, in cesarean section infants, there was a significant increase in the abundance of aac(6')-Ib genes at 2 months(β=3.81, Sx-=1.45, P<0.05), P<0.05] and 6 months of age (β=4.89, Sx-=1.11, P<0.001), P<0.001) compared to 3 days of age. Conclusions The findings suggest that IAP can increase the abundance of ARGs in 6-month-old infants, and this effect is still significant after stratifying by delivery mode. Therefore, the rational and standardized use of intrapartum antibiotics may help reduce the development of antibiotic resistance.
关键词
产时抗菌药物预防 /
肠道菌群 /
婴儿 /
耐药性
Key words
intrapartum antimicrobial prophylaxis /
gut microbiota /
infants /
antibiotic resistance
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基金
:国家自然科学基金(81872633);陕西省创新能力支撑计划(2023-CX-PT-47);国家留学基金委(CSC)资助项目(202006280219);中国博士后科学基金(2021M702578)
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