基因组毒力标志物与铜绿假单胞菌血流感染患者的严重预后相关。
Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection.
作者信息
Valik John Karlsson, Giske Christian G, Hasan Badrul, Gozalo-Margüello Mónica, Martínez-Martínez Luis, Premru Manica Mueller, Martinčič Žiga, Beović Bojana, Maraki Sofia, Zacharioudaki Maria, Kofteridis Diamantis, McCarthy Kate, Paterson David, Cueto Marina de, Morales Isabel, Leibovici Leonard, Babich Tanya, Granath Fredrik, Rodríguez-Baño Jesús, Oliver Antonio, Yahav Dafna, Nauclér Pontus
机构信息
Department of Medicine, Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden.
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
出版信息
Commun Med (Lond). 2024 Dec 11;4(1):264. doi: 10.1038/s43856-024-00696-4.
BACKGROUND
Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common healthcare-associated complication linked to antimicrobial resistance and high mortality. Ongoing clinical trials are exploring novel anti-virulence agents, yet studies on how bacterial virulence affects PA infection outcomes is conflicting and data from real-world clinical populations is limited.
METHODS
We studied a multicentre cohort of 773 adult patients with PA BSI consecutively collected during 7-years from sites in Europe and Australia. Comprehensive clinical data and whole-genome sequencing of all bacterial strains were obtained.
RESULTS
Based on the virulence genotype, we identify several virulence clusters, each showing varying proportions of multidrug-resistant phenotypes. Genes tied to biofilm synthesis and epidemic clones ST175 and ST235 are associated with mortality, while the type III secretion system is associated with septic shock. Adding genomic biomarkers to machine learning models based on clinical data indicates improved prediction of severe outcomes in PA BSI patients.
CONCLUSIONS
These findings suggest that virulence markers provide prognostic information with potential applications in guiding adjuvant sepsis treatments.
背景
铜绿假单胞菌（PA）血流感染（BSI）是一种常见的医疗相关并发症，与抗菌药物耐药性和高死亡率相关。正在进行的临床试验正在探索新型抗毒力药物，但关于细菌毒力如何影响PA感染结局的研究存在矛盾，且来自真实临床人群的数据有限。
方法
我们研究了一个多中心队列，该队列由773例成年PA BSI患者组成，这些患者是在7年期间从欧洲和澳大利亚的研究地点连续收集的。获得了所有细菌菌株的综合临床数据和全基因组测序结果。
结果
基于毒力基因型，我们识别出几个毒力簇，每个毒力簇显示出不同比例的多重耐药表型。与生物膜合成相关的基因以及流行克隆ST175和ST235与死亡率相关，而III型分泌系统与感染性休克相关。将基因组生物标志物添加到基于临床数据的机器学习模型中，表明对PA BSI患者严重结局的预测有所改善。
结论
这些发现表明，毒力标志物可提供预后信息，在指导脓毒症辅助治疗方面具有潜在应用价值。
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