肺炎克雷伯菌血流感染的死亡风险与特定的系统发育谱系有关。
Risk of death in Klebsiella pneumoniae bloodstream infections is associated with specific phylogenetic lineages.
作者信息
Fostervold Aasmund, Raffelsberger Niclas, Hetland Marit A K, Bakksjø Ragna, Bernhoff Eva, Samuelsen Ørjan, Sundsfjord Arnfinn, Afset Jan E, Berntsen Christopher F, Bævre-Jensen Roar, Ebbesen Marit H, Gammelsrud Karianne W, Guleng Anja D, Handal Nina, Jakovljev Aleksandra, Johal Simreen K, Marvik Åshild, Natvik Ane, Sandnes Rolf-Arne, Tofteland Ståle, Bjørnholt Jørgen V, Löhr Iren H
机构信息
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway; Department of Medical Microbiology, Stavanger University Hospital, Stavanger, Norway.
Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway; Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
出版信息
J Infect. 2024 May;88(5):106155. doi: 10.1016/j.jinf.2024.106155. Epub 2024 Apr 2.
BACKGROUND
Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear.
METHODS
In an 18-month nationwide Norwegian prospective study of KpSC BSI episodes in adults, we used whole-genome sequencing to describe the molecular epidemiology of KpSC, and multivariable Cox regression analysis including clinical data to determine adjusted hazard ratios (aHR) for death associated with specific genomic lineages.
FINDINGS
We included 1078 BSI episodes and 1082 bacterial isolates from 1055 patients. The overall 30-day case-fatality rate (CFR) was 12.5%. Median patient age was 73.4, 61.7% of patients were male. Median Charlson comorbidity score was 3. Klebsiella pneumoniae sensu stricto (Kp) (79.3%, n = 858/1082) and K. variicola (15.7%, n = 170/1082) were the dominating phylogroups. Global MDR-associated Kp clonal groups (CGs) were prevalent (25.0%, n = 270/1082) but 78.9% (n = 213/270) were not MDR, and 53.7% (n = 145/270) were community acquired. The major findings were increased risk for death within 30 days in monomicrobial BSIs caused by K. variicola (CFR 16.9%, n = 21; aHR 1.86, CI 1.10-3.17, p = 0.02), and global MDR-associated Kp CGs (CFR 17.0%, n = 36; aHR 1.52, CI 0.98-2.38, p = 0.06) compared to Kp CGs not associated with MDR (CFR 10.1%, n = 46).
CONCLUSION
Bacterial traits, beyond antimicrobial resistance, have a major impact on the clinical outcome of KpSC BSIs. The global spread of MDR-associated Kp CGs is driven by other mechanisms than antibiotic selection alone. Further insights into virulence determinants, and their association with phylogenetic lineages are needed to better understand the epidemiology of KpSC infection and clinical outcome.
背景
肺炎克雷伯菌复合种（KpSC）血流感染（BSIs）与相当高的发病率和死亡率相关，尤其是在老年和患有多种疾病的患者中。多重耐药（MDR）菌株与较差的预后相关。然而，KpSC系统发育谱系对血流感染结局的临床影响尚不清楚。
方法
在一项为期18个月的挪威全国性成人KpSC血流感染事件前瞻性研究中，我们使用全基因组测序来描述KpSC的分子流行病学，并进行多变量Cox回归分析（包括临床数据）以确定与特定基因组谱系相关的死亡调整风险比（aHR）。
结果
我们纳入了1055例患者的1078次血流感染事件和1082株细菌分离株。总体30天病死率（CFR）为12.5%。患者中位年龄为73.4岁，61.7%的患者为男性。Charlson合并症评分中位数为3。肺炎克雷伯菌狭义亚种（Kp）（79.3%，n = 858/1082）和 variicola克雷伯菌（15.7%，n = 170/1082）是主要的系统发育群。全球与MDR相关的Kp克隆群（CGs）很普遍（25.0%，n = 270/1082），但78.9%（n = 213/270）不是MDR，53.7%（n = 145/270）是社区获得性的。主要发现是，由variicola克雷伯菌引起的单微生物血流感染在30天内死亡风险增加（CFR 16.9%，n = 21；aHR 1.86，CI 1.10 - 3.17，p = 0.02），以及与全球MDR相关的Kp CGs（CFR 17.0%，n = 36；aHR 1.52，CI 0.98 - 2.38，p = 0.06）与非MDR相关的Kp CGs相比（CFR 10.1%，n = 46）。
结论
除抗菌药物耐药性外，细菌特征对KpSC血流感染的临床结局有重大影响。与MDR相关的Kp CGs的全球传播不仅仅是由抗生素选择驱动的。需要进一步深入了解毒力决定因素及其与系统发育谱系的关联，以更好地理解KpSC感染的流行病学和临床结局。
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