Ljungström Lars, Pernestig Anna-Karin, Jacobsson Gunnar, Andersson Rune, Usener Barbara, Tilevik Diana
Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
Systems Biology Research Centre, School of Bioscience, University of Skövde, Skövde, Sweden.
PLoS One. 2017 Jul 20;12(7):e0181704. doi: 10.1371/journal.pone.0181704. eCollection 2017.
Early recognition is a key factor to achieve improved outcomes for septic patients. Combinations of biomarkers, as opposed to single ones, may improve timely diagnosis and survival. We investigated the performance characteristics of sepsis biomarkers, alone and in combination, for diagnosis of verified bacterial sepsis using Sepsis-2 and Sepsis-3 criteria, respectively.
Procalcitonin (PCT), neutrophil-lymphocyte count ratio (NLCR), C-reactive protein (CRP), and lactate were determined in a total of 1,572 episodes of adult patients admitted to the emergency department on suspicion of sepsis. All sampling were performed prior to antibiotic administration. Discriminant analysis was used to construct two composite biomarkers consisting of linear combinations of the investigated biomarkers, one including three selected biomarkers (i.e., NLCR, CRP, and lactate), and another including all four (i.e., PCT, NLCR, CRP, and lactate). The diagnostic performances of the composite biomarkers as well as the individual biomarkers were compared using the area under the receiver operating characteristic curve (AUC).
For diagnosis of bacterial sepsis based on Sepsis-3 criteria, the AUC for PCT (0.68; 95% CI 0.65-0.71) was comparable to the AUCs for the both composite biomarkers. Using the Sepsis-2 criteria for bacterial sepsis diagnosis, the AUC for the NLCR (0.68; 95% CI 0.65-0.71) but not for the other single biomarkers, was equal to the AUCs for the both composite biomarkers. For diagnosis of severe bacterial sepsis or septic shock based on the Sepsis-2 criteria, the AUCs for both composite biomarkers were significantly greater than those of the single biomarkers (0.85; 95% CI 0.82-0.88 for the composite three-biomarker, and 0.86; 95% CI 0.83-0.89 for the composite four-biomarker).
Combinations of biomarkers can improve the diagnosis of verified bacterial sepsis in the most critically ill patients, but in less severe septic conditions either the NLCR or PCT alone exhibit equivalent performance.
早期识别是改善脓毒症患者预后的关键因素。与单一生物标志物相比，生物标志物组合可能会改善及时诊断和生存率。我们分别使用脓毒症-2和脓毒症-3标准，研究了脓毒症生物标志物单独及联合用于诊断确诊细菌性脓毒症的性能特征。
对总共1572例因疑似脓毒症而入住急诊科的成年患者进行了降钙素原（PCT）、中性粒细胞与淋巴细胞计数比值（NLCR）、C反应蛋白（CRP）和乳酸的检测。所有样本均在给予抗生素之前采集。采用判别分析构建由所研究生物标志物的线性组合组成的两种复合生物标志物，一种包括三种选定生物标志物（即NLCR、CRP和乳酸），另一种包括所有四种（即PCT、NLCR、CRP和乳酸）。使用受试者工作特征曲线下面积（AUC）比较复合生物标志物以及单个生物标志物的诊断性能。
对于基于脓毒症-3标准诊断细菌性脓毒症，PCT的AUC（0.68；95%CI 0.65-0.71）与两种复合生物标志物的AUC相当。使用脓毒症-2标准诊断细菌性脓毒症，NLCR的AUC（0.68；95%CI 0.65-0.71）与两种复合生物标志物的AUC相等，但其他单个生物标志物的AUC则不然。对于基于脓毒症-2标准诊断严重细菌性脓毒症或脓毒性休克，两种复合生物标志物的AUC均显著高于单个生物标志物（三种生物标志物组合的AUC为0.85；95%CI 0.82-0.88，四种生物标志物组合的AUC为0.86；95%CI 0.83-0.89）。
生物标志物组合可改善对最危重症患者确诊细菌性脓毒症的诊断，但在不太严重的脓毒症情况下，单独的NLCR或PCT表现出同等性能。
