Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital and University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Pediatrics, Spaarne Gasthuis, Hoofddorp and Haarlem, the Netherlands.
Nat Commun. 2022 Feb 16;13(1):893. doi: 10.1038/s41467-022-28525-z.
Broad-spectrum antibiotics for suspected early-onset neonatal sepsis (sEONS) may have pronounced effects on gut microbiome development and selection of antimicrobial resistance when administered in the first week of life, during the assembly phase of the neonatal microbiome. Here, 147 infants born at ≥36 weeks of gestational age, requiring broad-spectrum antibiotics for treatment of sEONS in their first week of life were randomized 1:1:1 to receive three commonly prescribed intravenous antibiotic combinations, namely penicillin + gentamicin, co-amoxiclav + gentamicin or amoxicillin + cefotaxime (ZEBRA study, Trial Register NL4882). Average antibiotic treatment duration was 48 hours. A subset of 80 non-antibiotic treated infants from a healthy birth cohort served as controls (MUIS study, Trial Register NL3821). Rectal swabs and/or faeces were collected before and immediately after treatment, and at 1, 4 and 12 months of life. Microbiota were characterized by 16S rRNA-based sequencing and a panel of 31 antimicrobial resistance genes was tested using targeted qPCR. Confirmatory shotgun metagenomic sequencing was executed on a subset of samples. The overall gut microbial community composition and antimicrobial resistance gene profile majorly shift directly following treatment (R= 9.5%, adjusted p-value = 0.001 and R= 7.5%, adjusted p-value = 0.001, respectively) and normalize over 12 months (R = 1.1%, adjusted p-value = 0.03 and R= 0.6%, adjusted p-value = 0.23, respectively). We find a decreased abundance of Bifidobacterium spp. and increased abundance of Klebsiella and Enterococcus spp. in the antibiotic treated infants compared to controls. Amoxicillin + cefotaxime shows the largest effects on both microbial community composition and antimicrobial resistance gene profile, whereas penicillin + gentamicin exhibits the least effects. These data suggest that the choice of empirical antibiotics is relevant for adverse ecological side-effects.
广谱抗生素用于疑似早发性新生儿败血症（sEONS）的治疗，可能会对肠道微生物组的发展产生显著影响，并在新生儿微生物组的组装阶段（即生命的第一周）选择抗生素耐药性。在此，147 名胎龄≥36 周、需要在生命的第一周内接受广谱抗生素治疗 sEONS 的婴儿，按照 1:1:1 的比例随机分为三组，分别接受三种常用的静脉注射抗生素组合，即青霉素+庆大霉素、复方阿莫西林+庆大霉素或阿莫西林+头孢噻肟（ZEBRA 研究，临床试验注册 NL4882）。平均抗生素治疗持续时间为 48 小时。作为对照，从健康出生队列中选择了 80 名未接受抗生素治疗的婴儿（MUIS 研究，临床试验注册 NL3821）。在治疗前、治疗后即刻以及 1、4 和 12 个月时采集直肠拭子和/或粪便。通过 16S rRNA 测序对微生物组进行特征分析，并使用靶向 qPCR 检测 31 种抗生素耐药基因。对部分样本进行了确认性的宏基因组测序。治疗后，肠道微生物群落组成和抗生素耐药基因谱主要发生变化（R=9.5%，调整后的 p 值=0.001 和 R=7.5%，调整后的 p 值=0.001），并在 12 个月内恢复正常（R=1.1%，调整后的 p 值=0.03 和 R=0.6%，调整后的 p 值=0.23）。与对照组相比，在接受抗生素治疗的婴儿中，双歧杆菌属的丰度降低，而克雷伯氏菌属和肠球菌属的丰度增加。与其他抗生素相比，阿莫西林+头孢噻肟对微生物群落组成和抗生素耐药基因谱的影响最大，而青霉素+庆大霉素的影响最小。这些数据表明，经验性抗生素的选择与不良的生态副作用有关。
