Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway.
Paediatric Research Group, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
J Antimicrob Chemother. 2018 Mar 1;73(3):569-580. doi: 10.1093/jac/dkx426.
To systematically review the impact of antibiotic therapy in the neonatal period on changes in the gut microbiota and/or antibiotic resistance development.
Data sources were PubMed, Embase, Medline and the Cochrane Database, supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic treatment (yes versus no, long versus short duration and/or broad- versus narrow-spectrum regimens) and subsequent changes in the gut microbiota and/or antibiotic resistance development. We evaluated risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, we used the vote-counting method to perform semi-quantitative meta-analyses. We applied the Grades of Recommendation, Assessment, Development and Evaluation approach to rate the quality of evidence (QoE). Study protocol registration: PROSPERO CRD42015026743.
We included 48 studies, comprising 3 RCTs and 45 observational studies. Prolonged antibiotic treatment was associated with reduced gut microbial diversity in all three studies investigating this outcome (very low QoE). Antibiotic treatment was associated with reduced colonization rates of protective commensal anaerobic bacteria in four of five studies (very low QoE). However, all three categories of antibiotic treatment were associated with an increased risk of antibiotic resistance development, in particular MDR in Gram-negative bacteria, and we graded the QoE for these outcomes as moderate.
We are moderately confident that antibiotic treatment leads to antibiotic resistance development in neonates and it may also induce potentially disease-promoting gut microbiota alterations. Our findings emphasize the need to reduce unnecessary antibiotic treatment in neonates.
系统综述新生儿期抗生素治疗对肠道微生物群变化和/或抗生素耐药发展的影响。
检索PubMed、Embase、Medline 和 Cochrane 数据库，并辅以手动检索参考文献。纳入了提供不同类别抗生素治疗（是/否、长疗程与短疗程和/或广谱与窄谱方案）以及随后肠道微生物群和/或抗生素耐药发展变化数据的随机对照试验（RCT）和观察性研究。我们使用 Cochrane 手册评估偏倚风险，该手册经过改编以纳入观察性研究。在适当情况下，我们使用投票计数法进行半定量荟萃分析。我们使用推荐、评估、制定和评估分级方法（Grades of Recommendation, Assessment, Development and Evaluation，GRADE）来评估证据质量（quality of evidence，QoE）。研究方案注册：PROSPERO CRD42015026743。
我们纳入了 48 项研究，包括 3 项 RCT 和 45 项观察性研究。三项研究均表明，延长抗生素治疗与所有三种研究结果的肠道微生物多样性降低相关（非常低的 QoE）。五项研究中的四项研究表明，抗生素治疗与保护性共生厌氧菌定植率降低相关（非常低的 QoE）。然而，所有三种类别的抗生素治疗均与抗生素耐药发展风险增加相关，特别是革兰氏阴性菌的 MDR，我们将这些结果的 QoE 评为中等。
我们有一定信心认为抗生素治疗会导致新生儿抗生素耐药发展，并且可能还会引起潜在促进疾病的肠道微生物群改变。我们的研究结果强调需要减少新生儿不必要的抗生素治疗。
