Early Inflammatory Markers for the Diagnosis of Late-Onset Sepsis in Neonates: The Nosodiag Study
Early Inflammatory Markers for the Diagnosis of Late-Onset Sepsis in Neonates: The Nosodiag Study
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DOI：
10.3389/fped.2018.00346
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发表时间：
2018-11-13
影响因子：
2.6
通讯作者：
Kuhn, Pierre
中科院分区：
文献类型：
--
作者：
Dillenseger, Laurence;Langlet, Claire;Kuhn, Pierre
背景：早期诊断对于改善新生儿院内细菌感染的治疗和预后至关重要。虽然细胞因子和降钙素原（PCT）已被评估为早期炎症标志物，但它们的诊断特性很少被比较。目的：本研究评估并比较了临床医生可用的单个炎症标志物的能力（PCT，IL-8的半定量测定）和标志物的组合（CRPi加IL-6或定量或半定量测定IL-8）来诊断新生儿细菌性医院感染。这项前瞻性双中心研究纳入了2008年9月至2012年1月期间疑似院内感染的新生儿。在怀疑医院感染时最初测量炎症标志物，并在12-24小时后再次测量CRP。新生儿被回顾性地分为两组：那些谁是感染（肯定或可能）和未感染（肯定或可能）。结果：该研究包括130例中位胎龄28周（范围，24-41周）的婴儿。其中34人被列为感染者，96人未被感染。敏感性、特异性、阳性和阴性预测值（PPV和NPV）以及阳性和阴性似然比PCT的LR+和LA-为59.3%（95%置信区间[Cl]，38.8-77.6%），78.5%（95% Cl，67.8-86.9%）、48.5%（95% Cl，30.8-66.5%）、84.9%（95% Cl，74.6-92.2%）、2.7（95% Cl，1.6-4.9）和0.5（95% Cl，0.3-0.8）。半定量IL-8的特异性最高（92.19%; 95% CI，82.70-97.41%），PPV（72.22%; 95% CI，46.52-90.30%）和LR+（6.17，95% CI，2.67-28.44），但特异性较低（48.15%; 95% CI，28.67-68.05%）。在所有检测的标志物中，IL-6和CRP的组合具有最高的灵敏度（78.12%; 95%CI，60.03-90.72%）、NPV（91.3%; 95%CI，82.38-96.32%）和LR-（0.29; 95%CI，0.12-0.49）。结论：IL-6和CRPi联合检测对新生儿医院感染的早期诊断具有上级优势，但单独检测仍有不足。IL-8的半定量测定具有良好的诊断特性，但其灵敏度太低，不能用于临床实践。
Background: Early diagnosis is essential to improve the treatment and prognosis of newborn infants with nosocomial bacterial infections. Although cytokines and procalcitonin (PCT) have been evaluated as early inflammatory markers, their diagnostic properties have rarely been compared.Objectives: This study evaluated and compared the ability of individual inflammatory markers available for clinician (PCT, semi-quantitative determination of IL-8) and of combinations of markers (CRPi plus IL-6 or quantitative or semi-quantitative determination of IL-8) to diagnose bacterial nosocomial infections in neonates.Methods: This prospective two-center study included neonates suspected of nosocomial infections from September 2008 to January 2012. Inflammatory markers were measured initially upon suspicion of nosocomial infection, and CRP was again measured 12-24 h later. Newborns were retrospectively classified into two groups: those who were infected (certainly or probably) and uninfected (certainly or probably).Results: The study included 130 infants of median gestational age 28 weeks (range, 24-41 weeks). Of these, 34 were classified as infected and 96 as uninfected. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LA-) for PCT were 59.3% (95% confidence interval [Cl], 38.8-77.6%), 78.5% (95% Cl, 67.8-86.9%), 48.5% (95% Cl, 30.8-66.5%), 84.9% (95% Cl, 74.6-92.2%), 2.7 (95% Cl, 1.6-4.9), and 0.5 (95% Cl, 0.3-0.8), respectively. Semi-quantitative IL-8 had the highest specificity (92.19%; 95% Cl, 82.70-97.41%), PPV (72.22%; 95% Cl, 46.52-90.30%) and LR+ (6.17, 95% Cl, 2.67-28.44), but had low specificity (48.15%; 95% Cl, 28.67-68.05%). Of all markers tested, the combination of IL-6 and CRP, had the highest sensitivity (78.12%; 95% Cl, 60.03-90.72%), NPV (91.3%; 95% Cl, 82.38-96.32%) and LR- (0.29; 95% Cl, 0.12-0.49). The combination of IL-6 and CRPi had a higher area under the curve than PCT, but with borderline significance (rho = 0.055).Conclusions: The combination of IL-6 and CRPi was superior to other methods, including PCT, for the early diagnosis of nosocomial infection in neonates, but was not sufficient for sole use. The semi-quantitative determination of IL-8 had good diagnostic properties but its sensitivity was too low for use in clinical practice.