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新生儿肺炎克雷伯菌败血症的临床与菌株分子特征研究
Clinical and molecular characteristics of neonatal Klebsiella pneumoniae sepsis
目的 探讨导致新生儿败血症的肺炎克雷伯菌的分子特征,分析其临床影响。 方法 收集河北省4家医院于2020—2024年间收治的新生儿肺炎克雷伯菌败血症患儿的临床资料及其血培养菌株,通过全基因组测序分析致病菌株的分子特征。比较毒力基因携带组与非携带组病例的临床特征,应用测序数据构建系统发育树,探究菌株潜在的传播方式。 结果 共纳入37例患儿及其临床分离肺炎克雷伯菌菌株。33例(89%)患儿为晚发型感染,其中32例(86%)为医院获得性感染。早产儿占95%,28例(76%)接受过侵入性操作,13例(35%)发病前有广谱抗菌药物暴露。所有患儿经过治疗后均治愈。菌株对第三代头孢菌素与碳青霉烯类药物的耐药率分别为89%、27%。ST45是致病菌株最常见的类型。超广谱β-内酰胺酶及碳青霉烯酶编码基因携带率分别为84%、24%。耐药基因与耐药表型一致率为86%,临床抗菌药物使用与耐药表型、耐药基因携带情况不完全一致。毒力基因中,ybt携带率最高(54%)。毒力基因携带组与非携带组合并其他部位感染的比例差异无统计学意义(50% vs 29%,P=0.315)。通过构建系统发育树,发现新生儿肺炎克雷伯菌败血症菌株存在院内与院际传播现象。 结论 菌株耐药基因与毒力基因检测有助于进一步加深对菌株致病机制的理解,为优化区域内感染防控策略及用药策略提供依据。
Objective To characterize the molecular profiles of Klebsiella pneumoniae isolates causing neonatal sepsis and assess their clinical implications. Methods Clinical data and bloodstream isolates from neonates with Klebsiella pneumoniae sepsis admitted to four hospitals in Hebei Province from 2020 to 2024 were collected. Whole-genome sequencing was performed to analyze molecular characteristics of the pathogenic strains. Clinical features were compared between virulence gene-carrying and non-carrying groups. A phylogenetic tree based on sequencing data was constructed to explore potential transmission routes. Results A total of 37 infants and their clinical bloodstream isolates were included. Thirty-three (89%) had late-onset infection, and 32 (86%) were hospital-acquired. Preterm infants accounted for 95%. Twenty-eight (76%) underwent invasive procedures, and 13 (35%) had prior exposure to broad-spectrum antimicrobials. All infants were cured after treatment. Resistance rates to third-generation cephalosporins and carbapenems were 89% and 27%, respectively. ST45 was the most common sequence type. The carriage rates of extended-spectrum β-lactamase and carbapenemase genes were 84% and 24%, respectively. Concordance between resistance genes and phenotypic resistance was 86%. Clinical antimicrobial use was not fully consistent with resistance phenotypes or gene carriage. Among virulence genes, ybt had the highest carriage rate (54%). The proportion of concurrent infections at other sites did not differ significantly between the virulence gene-carrying and non-carrying groups (50% vs 29%, P=0.315). Phylogenetic analysis revealed intra-hospital and inter-hospital transmission of Klebsiella pneumoniae strains causing neonatal sepsis. Conclusions Detection of antimicrobial resistance and virulence genes facilitates deeper understanding of bacterial pathogenesis and provides a basis for optimizing regional infection control and antimicrobial treatment strategies.
新生儿败血症 / 肺炎克雷伯菌 / 全基因组测序 / 多重耐药
Neonatal sepsis / Klebsiella pneumoniae / Whole-genome sequencing / Multidrug resistance
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所有作者声明无利益冲突。