Olie Sabine E, Staal Steven L, Groeneveld Nina S, Schotman Hans H M, Bodilsen Jacob, Nielsen Henrik, Bijlsma Merijn W, van de Beek Diederik, Brouwer Matthijs C
Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
European Society for Clinical Microbiology and Infectious Disease (ESCMID) Study Group on Infections of the Brain (ESGIB), Basel, Switzerland.
Lancet Reg Health Eur. 2025 Apr 29;53:101309. doi: 10.1016/j.lanepe.2025.101309. eCollection 2025 Jun.
C-reactive protein (CRP) in cerebrospinal fluid (CSF) was previously shown to be predictive for bacterial meningitis in patients with a suspected central nervous system (CNS) infection in an experimental study. We aimed to assess the diagnostic accuracy of CRP in CSF in a validation and clinical implementation study.
We validated CRP measurements in CSF for the diagnosis of bacterial meningitis in a Danish cohort of patients with acute CNS infections, and a Dutch cohort of pediatric patients suspected of a CNS infection. Subsequently, we evaluated the implementation of CRP measurements in CSF in clinical practice.
CRP in CSF was measured in 103 adult patients from Denmark, which included 34 (33%) bacterial meningitis patients. The AUC was 0.92 (95% CI: 0.85-0.99), and with a predefined cut-off of 0.3 mg/L, sensitivity was 85% (95% CI: 69-95) with a specificity of 96% (95% CI: 88-99). In 77 Dutch children, including 17 (22%) patients with bacterial meningitis, the AUC was 0.95 (95% CI: 0.87-1.00) and sensitivity and specificity were 94% (95% CI: 71-100) and 98% (95% CI: 91-100), respectively. From June 2024 to November 2024, we included 80 patients in our clinical implementation cohort, of which 15 (19%) were diagnosed with bacterial meningitis. The AUC for CRP in CSF was 0.99 (95% CI: 0.97-1.00), and sensitivity was 100% (95% CI: 78-100) with a specificity of 94% (95% CI: 85-99). Across all cohorts, the combination of CSF leukocytes and CSF CRP improved diagnostic accuracy compared to CSF leukocytes alone (p ≤ 0.001 in all cohorts).
CRP in CSF is a highly reliable predictor for bacterial meningitis, offering incremental value in addition to CSF leukocytes. Clinical implementation is straightforward and can be achieved at low costs in laboratories where CRP in blood is already routinely measured.
Supported by the European Research Council (ERC Consolidator grant 101001237 to MB) and the Netherlands Organisation for Health Research and Development (ZonMw; NWO-Vidi Grant [917.17.308] to MCB; NWO-Vici-Grant Grant [918.19.627] to DvdB).
在一项实验研究中，脑脊液（CSF）中的C反应蛋白（CRP）先前已被证明对疑似中枢神经系统（CNS）感染的患者的细菌性脑膜炎具有预测作用。我们旨在通过一项验证和临床实施研究来评估CSF中CRP的诊断准确性。
我们在丹麦一组急性CNS感染患者以及荷兰一组疑似CNS感染的儿科患者中验证了CSF中CRP测量对细菌性脑膜炎的诊断价值。随后，我们评估了CSF中CRP测量在临床实践中的实施情况。
对来自丹麦的103例成年患者的CSF进行了CRP测量，其中包括34例（33%）细菌性脑膜炎患者。曲线下面积（AUC）为0.92（95%置信区间：0.85 - 0.99），预定义临界值为0.3 mg/L时，敏感性为85%（95%置信区间：69 - 95），特异性为96%（95%置信区间：88 - 99）。在77例荷兰儿童中，包括17例（22%）细菌性脑膜炎患者，AUC为0.95（95%置信区间：0.87 - 1.00），敏感性和特异性分别为94%（95%置信区间：71 - 100）和98%（95%置信区间：91 - 100）。从2024年6月至2024年11月，我们的临床实施队列纳入了80例患者，其中15例（19%）被诊断为细菌性脑膜炎。CSF中CRP的AUC为0.99（95%置信区间：0.97 - 1.00），敏感性为100%（95%置信区间：78 - 100），特异性为94%（95%置信区间：85 - 99）。在所有队列中，与单独的CSF白细胞相比，CSF白细胞和CSF CRP的联合使用提高了诊断准确性（所有队列中p≤0.001）。
CSF中的CRP是细菌性脑膜炎的高度可靠预测指标，除CSF白细胞外还具有额外价值。临床实施简单直接，在已常规测量血液中CRP的实验室中可以低成本实现。
由欧洲研究理事会（ERC整合者资助项目101001237给MB）和荷兰卫生研究与发展组织（ZonMw；NWO - Vidi资助项目[917.17.308]给MCB；NWO - Vici资助项目[918.19.627]给DvdB）提供支持。
