OBJECTIVES To identify risk stratification biomarkers to enrich for the subset of Staphylococcus aureus bacteraemia patients who develop deep-seated tissue infections with high morbidity and mortality to guide clinical trial enrolment and clinical management. METHODS We evaluated the prognostic value of eight biomarkers for persistent bacteraemia, mortality and endovascular infection foci in a validation cohort of 160 patients with S. aureus bacteraemia enrolled consecutively over 3 years. RESULTS 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. CONCLUSION 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.

中文翻译：

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金黄色葡萄球菌菌血症的风险分层生物标志物。

目的 确定风险分层生物标志物，以丰富发生深部组织感染且发病率和死亡率高的金黄色葡萄球菌菌血症患者亚群，以指导临床试验入组和临床管理。方法 我们在 160 名金黄色葡萄球菌菌血症患者的验证队列中评估了 8 种生物标志物对持续性菌血症、死亡率和血管内感染病灶的预后价值，该队列连续纳入 3 年以上。结果 菌血症诊断时高水平的 IL-17A、IL-10 或可溶性 E-选择素与阳性血培养的持续时间相关。当应用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有力预测指标。IL-17A 和 IL-10 的高血清水平通常在感染性心内膜炎的放射影像学诊断之前，这表明优先考虑放射影像学诊断的潜在效用。高 IL-8 可预测全因死亡率，而 IL-17A 和 IL-10 在区分可归因死亡率和不可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 确定的发生微生物学失败或死亡的患者更多。结论 这些生物标志物为识别有持续性菌血症风险的患者提供了潜在的效用，以指导诊断成像和临床管理。低生物标志物水平可用于排除感染性心内膜炎风险较低的患者需要更多侵入性 TEE 成像。