Cao Yi, Guimaraes Alessander O, Peck Melicent C, Mayba Oleg, Ruffin Felicia, Hong Kyu, Carrasco-Triguero Montserrat, Fowler Vance G, Maskarinec Stacey A, Rosenberger Carrie M
Bioinformatics and Computational Biology Genentech, Inc. South San Francisco CA USA.
Biomarker Discovery Genentech, Inc. South San Francisco CA USA.
Clin Transl Immunology. 2020 Feb 13;9(2):e1110. doi: 10.1002/cti2.1110. eCollection 2020.
To identify risk stratification biomarkers to enrich for the subset of bacteraemia patients who develop deep-seated tissue infections with high morbidity and mortality to guide clinical trial enrolment and clinical management.
We evaluated the prognostic value of eight biomarkers for persistent bacteraemia, mortality and endovascular infection foci in a validation cohort of 160 patients with bacteraemia enrolled consecutively over 3 years.
High levels of IL-17A, IL-10 or soluble E-selectin at bacteraemia diagnosis correlated with the duration of positive blood cultures. When thresholds defined in an independent cohort were applied, these biomarkers were robust predictors of persistent bacteraemia or endovascular infection. High serum levels of IL-17A and IL-10 often preceded the radiographic diagnosis of infective endocarditis, suggesting potential utility for prioritising diagnostic radiographic imaging. High IL-8 was prognostic for all-cause mortality, while IL-17A and IL-10 were superior to clinical metrics in discriminating between attributable mortality and non-attributable mortality. High IL-17A and IL-10 identified more patients who developed microbiological failure or mortality than were identified by infective endocarditis diagnosis.
These biomarkers offer potential utility to identify patients at risk of persistent bacteraemia to guide diagnostic imaging and clinical management. Low biomarker levels could be used to rule out the need for more invasive TEE imaging in patients at lower risk of infective endocarditis. These biomarkers could enable clinical trials by enriching for patients with the greatest need for novel therapies.
识别风险分层生物标志物,以富集发生深部组织感染且发病率和死亡率高的菌血症患者亚组,从而指导临床试验入组和临床管理。
我们评估了8种生物标志物对持续性菌血症、死亡率和血管内感染灶的预后价值,研究对象为连续3年纳入的160例菌血症患者组成的验证队列。
菌血症诊断时白细胞介素-17A(IL-17A)、白细胞介素-10(IL-10)或可溶性E选择素水平升高与血培养阳性持续时间相关。应用在独立队列中定义的阈值时,这些生物标志物是持续性菌血症或血管内感染的可靠预测指标。血清IL-17A和IL-10水平升高常先于感染性心内膜炎的影像学诊断,提示其在优先进行诊断性影像学检查方面的潜在效用。高白细胞介素-8(IL-8)水平对全因死亡率具有预后价值,而IL-17A和IL-10在区分归因死亡率和非归因死亡率方面优于临床指标。与感染性心内膜炎诊断相比,高IL-17A和IL-10水平识别出更多发生微生物学治疗失败或死亡的患者。
这些生物标志物有助于识别有持续性菌血症风险的患者,以指导诊断性影像学检查和临床管理。低生物标志物水平可用于排除感染性心内膜炎风险较低患者进行更具侵入性的经食管超声心动图(TEE)检查的必要性。这些生物标志物可通过富集最需要新疗法的患者来推动临床试验。