Groeneveld Nina S, Bijlsma Merijn W, van de Beek Diederik, Brouwer Matthijs C
Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Centres, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands.
Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Centres, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands; Department of Paediatrics, Amsterdam Neuroscience, Amsterdam University Medical Centres, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands.
Clin Microbiol Infect. 2025 May;31(5):702-712. doi: 10.1016/j.cmi.2024.12.009. Epub 2024 Dec 12.
Biomarkers for paediatric bacterial meningitis are essential for an accurate diagnosis.
To perform a systematic review of diagnostic accuracy on cerebrospinal fluid (CSF) and blood biomarkers for paediatric bacterial meningitis.
Databases Medline, Excerpta Medica Database, Scopus, and Web of Science were used.
Eligible studies were those on novel diagnostic CSF and blood biomarkers from which data on biomarker concentration or diagnostic accuracy could be abstracted.
Paediatric patients (0-18 years) suspected of a central nervous system (CNS) infection.
The Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS)-2 tool was used to assess risk of bias.
The difference in biomarker concentrations were assessed by calculating standardized and weighted mean differences. A random-effects meta-analysis model was used. Hierarchical summary receiver-operating characteristic curves were constructed.
We identified 3435 studies, of which 112 articles on 113 individual biomarkers (CSF n = 90 and blood n = 23) were included. In CSF, C-reactive protein (CRP), Interleukin (IL)-6, Tumor necrosis factor (TNF)-α, and Interleukin (IL)-8 showed the largest mean differences between bacterial meningitis and viral meningitis and IL-6, TNF-α, and IL-8 between bacterial meningitis and no CNS infection/inflammation. CSF CRP and ferritin showed excellent discrimination for bacterial versus viral meningitis (summary area under the curve [sAUC] 0.94; 95% CI, 0.92-0.97, sAUC 0.94; 95% CI, 0.90-1.0). CSF IL-6 and procalcitonin showed excellent discrimination for bacterial versus nonbacterial meningitis and versus no CNS infection/inflammation (sAUC IL-6: 0.98; 95% CI, 0.96-1.00, sAUC procalcitonin: 0.96; 95% CI, 0.94-0.99). Procalcitonin in blood showed good discrimination (AUC, 0.89; 95% CI, 0.68-1.00).
We identified several CSF biomarkers with high diagnostic accuracy for the diagnosis of bacterial meningitis, including IL-6, procalcitonin, CRP, and ferritin. None of the blood biomarkers exhibited excellent discrimination for paediatric bacterial meningitis. Validation of these biomarkers in prospective, well-designed studies of diagnostic accuracy performed in children with suspected meningitis is needed.
小儿细菌性脑膜炎的生物标志物对于准确诊断至关重要。
对小儿细菌性脑膜炎脑脊液（CSF）和血液生物标志物的诊断准确性进行系统评价。
使用了Medline、医学文摘数据库、Scopus和科学引文索引数据库。
符合条件的研究为关于新型诊断性CSF和血液生物标志物的研究，从中可提取生物标志物浓度或诊断准确性的数据。
疑似中枢神经系统（CNS）感染的儿科患者（0 - 18岁）。
使用诊断准确性研究质量评估工具（QUADAS）-2工具评估偏倚风险。
通过计算标准化和加权平均差异来评估生物标志物浓度的差异。使用随机效应荟萃分析模型。构建分层汇总受试者工作特征曲线。
我们识别出3435项研究，其中纳入了112篇关于113种个体生物标志物的文章（CSF中90种，血液中23种）。在CSF中，C反应蛋白（CRP）、白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-8在细菌性脑膜炎和病毒性脑膜炎之间显示出最大的平均差异，IL-6、TNF-α和IL-8在细菌性脑膜炎和无CNS感染/炎症之间显示出最大的平均差异。CSF CRP和铁蛋白对细菌性与病毒性脑膜炎具有出色的鉴别能力（曲线下面积汇总值[sAUC] 0.94；95%置信区间，0.92 - 0.97，sAUC 0.94；95%置信区间，0.90 - 1.0）。CSF IL-6和降钙素原对细菌性与非细菌性脑膜炎以及与无CNS感染/炎症具有出色的鉴别能力（sAUC IL-6：0.98；95%置信区间，0.96 - 1.00，sAUC降钙素原：0.96；95%置信区间，0.94 - 0.99）。血液中的降钙素原显示出良好的鉴别能力（AUC，0.89；95%置信区间，0.68 - 1.00）。
我们识别出几种对细菌性脑膜炎诊断具有高诊断准确性的CSF生物标志物，包括IL-6、降钙素原、CRP和铁蛋白。没有一种血液生物标志物对小儿细菌性脑膜炎具有出色的鉴别能力。需要在对疑似脑膜炎儿童进行的前瞻性、设计良好的诊断准确性研究中对这些生物标志物进行验证。
