Background Diagnosis of bacterial meningitis (BM) is challenging in newborn infants. Presently, biomarkers of BM have limited diagnostic accuracy. Analysis of cerebrospinal fluid (CSF) metabolites may be a useful diagnostic tool in BM. Methods In a nested case–control study, we examined >400 metabolites in CSF of uninfected infants and infants with culture-confirmed BM using gas and liquid chromatography mass spectrometry. Preterm and full-term infants in a Level III or IV Neonatal Intensive Care Unit were prospectively enrolled when evaluated for serious bacterial infection. Results Over 200 CSF metabolites significantly differed in uninfected infants and infants with BM. Using machine learning, we found that as few as 6 metabolites distinguished infants with BM from uninfected infants in this pilot cohort. Further analysis demonstrated three metabolites associated with Group B Streptococcal meningitis. Conclusions We report the first comprehensive metabolic analysis of CSF in infants with BM. In our pilot cohort, we derived a metabolic signature that predicted the presence or absence of BM, irrespective of gestational age, postnatal age, sex, race and ethnicity, presence of neurosurgical hardware, white blood cell count in CSF, and red blood cell contamination in CSF. Metabolic analysis may aid diagnosis of BM and facilitate clinical decision-making in infants. Impact In a pilot cohort, metabolites in cerebrospinal fluid distinguished infants with bacterial meningitis from uninfected infants. We report the first comprehensive metabolic analysis of cerebrospinal fluid in infants with bacterial meningitis. Our findings may be used to improve diagnosis of bacterial meningitis and to offer mechanistic insights into the pathophysiology of bacterial meningitis in infants.

中文翻译：

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推导与婴儿细菌性脑膜炎相关的代谢特征

背景 新生儿细菌性脑膜炎 (BM) 的诊断具有挑战性。目前，BM 的生物标志物的诊断准确性有限。脑脊液 (CSF) 代谢物的分析可能是 BM 中有用的诊断工具。方法 在一项巢式病例对照研究中，我们使用气相和液相色谱质谱法检测了未感染婴儿和经培养证实为 BM 的婴儿脑脊液中超过 400 种代谢物。在评估严重细菌感染时，前瞻性招募了 III 级或 IV 级新生儿重症监护室的早产儿和足月儿。结果 200 多种 CSF 代谢物在未感染婴儿和 BM 婴儿中存在显着差异。使用机器学习，我们发现在这个试点队列中，只有 6 种代谢物可以区分患有 BM 的婴儿和未感染的婴儿。进一步的分析表明，三种代谢物与 B 组链球菌性脑膜炎有关。结论 我们报告了 BM 婴儿脑脊液的首次综合代谢分析。在我们的试点队列中，我们得出了预测 BM 存在或不存在的代谢特征，与胎龄、产后年龄、性别、种族和民族、神经外科硬件的存在、CSF 中的白细胞计数和红细胞污染无关在脑脊液中。代谢分析可能有助于诊断 BM 并促进婴儿的临床决策。影响 在一个试点队列中，脑脊液中的代谢物将患有细菌性脑膜炎的婴儿与未感染的婴儿区分开来。我们报告了对细菌性脑膜炎婴儿脑脊液的首次综合代谢分析。