There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of diagnosis. The levels of 17 cytokines in plasma were measured in 341 CDI inpatients. The primary outcome of interest was 90-day mortality. Increased tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 5 (CCL-5), suppression of tumorigenicity 2 receptor (sST-2), IL-8, and IL-15 predicted mortality by univariate analysis. After adjusting for demographics and clinical characteristics, the mortality risk (as indicated by the hazard ratio [HR]) was higher for patients in the top 25th percentile for TNF-α (HR = 8.35, P = 0.005) and IL-8 (HR = 4.45, P = 0.01) and lower for CCL-5 (HR = 0.18, P ≤ 0.008). A logistic regression risk prediction model was developed and had an area under the receiver operating characteristic curve (AUC) of 0.91 for 90-day mortality and 0.77 for 90-day recurrence. While limited by being single site and retrospective, our work resulted in a model with a substantially greater predictive ability than white blood cell count. In conclusion, immune profiling demonstrated differences between patients in their response to CDI, offering the promise for precision medicine individualized treatment.

中文翻译：

---

免疫分析预测艰难梭菌感染的结果。

迫切需要基于生物标志物的模型来预测艰难梭菌的死亡率和复发率感染（CDI）。风险分层将使有针对性的干预措施成为可能，例如对高危人群进行粪便微生物群移植、抗毒素抗体和结肠切除术。由于 CDI 的严重程度与免疫反应相关，我们在诊断时对患者进行免疫分析。在 341 名 CDI 住院患者中测量了血浆中 17 种细胞因子的水平。感兴趣的主要结果是 90 天死亡率。肿瘤坏死因子 α (TNF-α)、白介素 6 (IL-6)、CC 基序趋化因子配体 5 (CCL-5)、致瘤性 2 受体 (sST-2)、IL-8 和 IL-15 预测的抑制增加单变量分析死亡率。在调整人口统计学和临床​​特征后，TNF-α 处于前 25 个百分位的患者的死亡风险（如风险比 [HR] 所示）更高（HR = 8.35，P= 0.005) 和 IL-8 (HR = 4.45, P = 0.01) 和更低的 CCL-5 (HR = 0.18, P ≤ 0.008)。开发了逻辑回归风险预测模型，90 天死亡率的受试者操作特征曲线 (AUC) 下面积为 0.91，90 天复发率为 0.77。虽然受到单一站点和回顾性的限制，但我们的工作产生了一个比白细胞计数具有更大预测能力的模型。总之，免疫分析表明患者对 CDI 的反应存在差异，为精准医学个体化治疗提供了希望。