新生儿败血症是一种高死亡率的危及生命的疾病。与引起革兰氏阴性（GN）新生儿败血症相关的毒力决定因素仍然缺乏表征。更好地了解与GN新生儿败血症相关的毒力因子（VFs）可以为治疗干预提供新的靶点。这篇综述的目的是评估GNVFs在新生儿败血症中的作用。我们的主要目的是调查导致不良结局的主要VFs，其次是评估与新生儿侵袭性/致病性增加相关的VFs。MEDLINE,Embase,和CochraneLibrary进行了系统搜索，以获得有关病毒体/VFs在新生儿和0-90日龄婴儿肠杆菌引起的血流感染中的作用的研究数据。20项研究符合纳入标准。只有4项研究报告了病原体毒力决定因素与新生儿死亡率之间关联的数据，而16项研究纳入次要分析.在绝大多数已发表的研究中，报告的质量并不理想。未发现毒力决定子与引起新生儿败血症的GN菌株之间的一致关联。在分析和报告的VF方面发现了相当大的异质性，包括种群和微生物学方法，纳入的研究经常显示相互矛盾的数据。这种可变性妨碍了结果的比较。在结论中，导致新生儿败血症的病原体具有广泛的异质性，可以使用不同的途径发展为侵袭性疾病。最近的全基因组方法需要包括具有更大样本量的多中心研究，分析VF基因图谱而不是单个VF基因，以及全面的临床信息收集。更好地了解毒力基因在新生儿GN菌血症中的作用可能会提供新的疫苗靶标和高毒力菌株的新标记。该信息可潜在地用于筛查和预防性干预以及抗毒性抗生素保留疗法的新靶标。
Neonatal sepsis is a life-threatening condition with high mortality. Virulence determinants relevant in causing Gram-negative (GN) neonatal sepsis are still poorly characterized. A better understanding of virulence factors (VFs) associated with GN neonatal sepsis could offer new targets for therapeutic interventions. The aim of this
review was to assess the role of GN VFs in neonatal sepsis. We primarily aimed to investigate the main VFs leading to adverse outcome and second to evaluate VFs associated with increased invasiveness/pathogenicity in neonates. MEDLINE, Embase, and Cochrane Library were systematically searched for studies reporting data on the role of
virulome/VFs in bloodstream infections caused by Enterobacterales among neonates and infants aged 0-90 days. Twenty studies fulfilled the inclusion criteria. Only 4 studies reported data on the association between pathogen virulence determinants and neonatal mortality, whereas 16 studies were included in the secondary analyses. The quality of reporting was suboptimal in the great majority of the published studies. No consistent association between virulence determinants and GN strains causing neonatal sepsis was identified. Considerable heterogeneity was found in terms of VFs analysed and reported, included population and microbiological methods, with the included studies often showing conflicting data. This variability hampered the comparison of the results. In conclusions, pathogens responsible for neonatal sepsis are widely heterogenous and can use different pathways to develop invasive disease. The recent genome-wide approach needs to include multicentre studies with larger sample sizes, analyses of VF gene profiles instead of single VF genes, alongside a comprehensive collection of clinical information. A better understanding of the roles of virulence genes in neonatal GN bacteraemia may offer new vaccine targets and new markers of highly virulent strains. This information can potentially be used for screening and preventive interventions as well as for new targets for anti-virulence antibiotic-sparing therapies.
