Novel Biomarkers, Including tcdB PCR Cycle Threshold, for Predicting Recurrent Clostridioides difficile Infection.
Novel Biomarkers, Including tcdB PCR Cycle Threshold, for Predicting Recurrent Clostridioides difficile Infection.
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DOI：
10.1128/iai.00092-23
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发表时间：
2023-04-18
影响因子：
3.1
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中科院分区：
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预测复发性艰难梭菌感染的传统临床模型表现不佳，可能是由于涉及复杂的宿主-病原体相互作用。使用新型生物标志物进行准确的风险分层可以通过改善有效疗法（即粪便移植、非达索霉素、bezlotoxumab）的利用不足来帮助预防复发。我们使用了257名住院患者的生物库，在诊断时收集了24个特征，包括17个血浆细胞因子、总/中和抗毒素B IgG、粪便毒素和PCR周期阈值（CT）（粪便微生物负担的代表）。通过贝叶斯模型平均选出复发感染的最佳预测因子集，纳入最终的贝叶斯逻辑回归模型。然后，我们使用大量仅PCR的数据集来证实PCR CT使用Cox比例风险回归预测无复发生存的发现。最高的模型平均特征为（概率为>.05，从大到小）：白细胞介素6 （IL-6）、PCR CT、内皮生长因子、IL-8、eotaxin、IL-10、肝细胞生长因子和IL-4。最终模型的精度为0.88。在仅有pcr数据的1,660例患者中，周期阈值与无复发生存显著相关（风险比，0.95;P < 0.005）。某些与艰难梭菌感染严重程度相关的生物标志物对预测复发尤其重要；PCR CT和2型免疫标志物（内皮生长因子[EGF]， eotaxin）是复发的阳性预测因子，而17型免疫标志物（IL-6, IL-8）是复发的阴性预测因子。除了新的血清生物标志物（特别是IL-6， EGF和IL-8），现成的PCR CT可能对增加表现不佳的艰难梭菌复发的临床模型至关重要。
Traditional clinical models for predicting recurrent Clostridioides difficile infection do not perform well, likely owing to the complex host-pathogen interactions involved. Accurate risk stratification using novel biomarkers could help prevent recurrence by improving underutilization of effective therapies (i.e., fecal transplant, fidaxomicin, bezlotoxumab). We used a biorepository of 257 hospitalized patients with 24 features collected at diagnosis, including 17 plasma cytokines, total/neutralizing anti-toxin B IgG, stool toxins, and PCR cycle threshold (CT) (a proxy for stool organism burden). The best set of predictors for recurrent infection was selected by Bayesian model averaging for inclusion in a final Bayesian logistic regression model. We then used a large PCR-only data set to confirm the finding that PCR CT predicts recurrence-free survival using Cox proportional hazards regression. The top model-averaged features were (probabilities of >0.05, greatest to least): interleukin 6 (IL-6), PCR CT, endothelial growth factor, IL-8, eotaxin, IL-10, hepatocyte growth factor, and IL-4. The accuracy of the final model was 0.88. Among 1,660 cases with PCR-only data, cycle threshold was significantly associated with recurrence-free survival (hazard ratio, 0.95; P < 0.005). Certain biomarkers associated with C. difficile infection severity were especially important for predicting recurrence; PCR CT and markers of type 2 immunity (endothelial growth factor [EGF], eotaxin) emerged as positive predictors of recurrence, while type 17 immune markers (IL-6, IL-8) were negative predictors. In addition to novel serum biomarkers (particularly, IL-6, EGF, and IL-8), the readily available PCR CT may be critical to augment underperforming clinical models for C. difficile recurrence.
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影响因子：
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