Department of Clinical Pharmacy, University of Southern California (USC) School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA, 90089, USA.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA.
BMC Infect Dis. 2021 Apr 5;21(1):317. doi: 10.1186/s12879-021-06010-0.
We demonstrated that an early dysregulated cytokine response [high interleukin-10 to tissue necrosis factor (IL-10/TNF) ratio] predicted poor outcomes in patients with Staphylococcus aureus bacteremia (SAB). However, high interpatient variability in cytokine levels were observed. We grouped cytokine measurements in quartiles and assessed their additive value to clinical variables for predicting bacterial persistence and 30-day mortality in patients with SAB.
A multicenter observational study was conducted in hospitalized patients with SAB. Medical charts were reviewed for relevant information. Blood samples were obtained for cytokine measurements by ELISA: interferon-gamma (IFNγ), interleukin (IL-1β, IL-6, IL-8, IL-10, IL-17) and tissue necrosis factor (TNF). Cytokine measurements were grouped into quartiles. Significant predictors for bacterial persistence and 30-day mortality were determined by multivariable logistic regression analysis. Area under the ROC curve (AUC) analysis was performed and predictive performance was compared between models with and without cytokine quartiles.
Among 606 patients with SAB, a subset of patients (n = 239) had Day 1 cytokine measurements and clinical data collected; of those, 53 (22%) had persistent bacteremia. Accounting for septic shock, the addition of either IL-10 (AUC 0.708) or TNF (AUC 0.714) quartiles measured on Day 1 improved model performance for predicting bacterial persistence. All patients had Day 4 cytokine measurements; 52 patients (8.5%) died within 30-days of SAB onset. Inclusion of either IL-10 (AUC 0.873) or TNF (AUC 0.879) quartiles, but not both, measured on Day 4 to the significant clinical predictors (coronary artery disease, Pitt bacteremia score ≥ 4, and septic shock) improved model performance for mortality.
IL-10 or TNF levels falling within the range in the upper quartiles, when combined with clinical variables, improved model performance for predicting outcomes, and may potentially be used to support aggressive management and biomarker-guided studies to evaluate the benefit of adjunctive immunotherapy for SAB in the future.
我们发现，细胞因子反应早期失调[白细胞介素-10 与组织坏死因子（IL-10/TNF）比值高]可预测金黄色葡萄球菌菌血症（SAB）患者的不良结局。然而，细胞因子水平的个体间变异性很大。我们将细胞因子测量值分为四组，并评估其对临床变量的附加价值，以预测 SAB 患者的细菌持续存在和 30 天死亡率。
进行了一项多中心观察性研究，纳入了 SAB 住院患者。回顾病历以获取相关信息。通过 ELISA 测定血液样本中的细胞因子：干扰素-γ（IFNγ）、白细胞介素（IL-1β、IL-6、IL-8、IL-10、IL-17）和肿瘤坏死因子（TNF）。将细胞因子测量值分为四组。通过多变量逻辑回归分析确定细菌持续存在和 30 天死亡率的显著预测因素。进行 ROC 曲线下面积（AUC）分析，并比较有和无细胞因子四分位数的模型的预测性能。
在 606 例 SAB 患者中，有一部分患者（n=239）在第 1 天采集了细胞因子测量值和临床数据；其中，53 例（22%）发生持续菌血症。在考虑感染性休克的情况下，第 1 天测量的 IL-10（AUC 0.708）或 TNF（AUC 0.714）四分位数的加入均改善了预测细菌持续存在的模型性能。所有患者均在第 4 天进行了细胞因子测量；52 例（8.5%）在 SAB 发病后 30 天内死亡。在包括 IL-10（AUC 0.873）或 TNF（AUC 0.879）四分位数在内的模型中，仅纳入第 4 天测量的 IL-10 或 TNF 四分位数，而不是两者，与显著的临床预测因素（冠状动脉疾病、Pitt 菌血症评分≥4 和感染性休克）相结合，提高了死亡率的模型性能。
当与临床变量结合使用时，IL-10 或 TNF 水平处于四分位数的较高范围，可改善预测结局的模型性能，并且可能有助于支持积极的管理和生物标志物指导的研究，以评估未来 SAB 辅助免疫治疗的获益。
