Department of Paediatrics, Children Hospital V. Buzzi, University of Milan, 20154 Milan, Italy.
Division of Neonatology, "F. Del Ponte" Hospital, Woman and Child Department, University of Insubria, 21100 Varese, Italy.
Int J Mol Sci. 2022 Oct 8;23(19):11930. doi: 10.3390/ijms231911930.
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 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.
新生儿败血症是一种危及生命的疾病，死亡率很高。导致革兰氏阴性（GN）新生儿败血症的毒力决定因素仍未得到很好的描述。更好地了解与 GN 新生儿败血症相关的毒力因子（VFs）可能为治疗干预提供新的目标。本综述的目的是评估 GN VFs 在新生儿败血症中的作用。我们主要旨在研究导致不良结局的主要 VFs，并评估与新生儿侵袭性/致病性增加相关的 VFs。系统地检索了 MEDLINE、Embase 和 Cochrane Library 中的研究，以报告关于在 0-90 天龄的新生儿和婴儿中血流感染的病毒组/ VFs 对病毒血症的作用的数据。有 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的关联数据，而 16 项研究被纳入次要分析。已发表研究的报告质量绝大多数都不理想。未发现毒力决定因素与引起新生儿败血症的 GN 菌株之间存在一致的关联。在分析和报告的 VFs、纳入人群和微生物学方法方面存在相当大的异质性，所纳入的研究经常显示出相互矛盾的数据。这种变异性阻碍了结果的比较。总之，导致新生儿败血症的病原体具有广泛的异质性，并且可以使用不同的途径发展侵袭性疾病。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，对 VF 基因谱进行分析而不是单个 VF 基因，以及全面收集临床信息。更好地了解毒力基因在新生儿 GN 菌血症中的作用可能为新的疫苗靶点和高度毒力菌株的新标志物提供依据。这些信息可用于筛选和预防干预措施以及抗毒力抗生素节约疗法的新靶点。
