Srinivasan Lakshmi, Kilpatrick Laurie, Shah Samir S, Abbasi Soraya, Harris Mary C
Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania; Philadelphia, Pennsylvania.
Pediatr Res. 2016 Oct;80(4):566-72. doi: 10.1038/pr.2016.117. Epub 2016 May 26.
Bacterial meningitis poses diagnostic challenges in infants. Antibiotic pretreatment and low bacterial density diminish cerebrospinal fluid (CSF) culture yield, while laboratory parameters do not reliably identify bacterial meningitis. Pro and anti-inflammatory cytokines are elevated in bacterial meningitis and may be useful diagnostic adjuncts when CSF cultures are negative.
In a prospective cohort study of infants, we used cytometric bead arrays to measure tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), IL-6, IL-8, IL-10, and IL-12 in CSF. Receiver operating characteristic (ROC) analyses and Principal component analysis (PCA) were used to determine cytokine combinations that identified bacterial meningitis.
Six hundred and eighty four infants < 6 mo were included; 11 had culture-proven bacterial meningitis. IL-6 and IL-10 were the individual cytokines possessing greatest accuracy in diagnosis of culture proven bacterial meningitis (ROC analyses; area under the concentration-time curve (AUC) 0.91; 0.9103 respectively), and performed as well as, or better than combinations identified using ROC and PCA. CSF cytokines were highly correlated with each other and with CSF white blood cell count (WBC) counts in infants with meningitis. A subset of antibiotic pretreated culture-negative subjects demonstrated cytokine patterns similar to culture positive subjects.
CSF cytokine levels may aid diagnosis of bacterial meningitis, and facilitate decision-making regarding treatment for culture negative meningitis.
细菌性脑膜炎给婴儿的诊断带来挑战。抗生素预处理和低细菌密度会降低脑脊液（CSF）培养的阳性率，而实验室参数不能可靠地识别细菌性脑膜炎。促炎和抗炎细胞因子在细菌性脑膜炎中升高，当CSF培养结果为阴性时，它们可能是有用的诊断辅助指标。
在一项针对婴儿的前瞻性队列研究中，我们使用细胞计数珠阵列来测量CSF中的肿瘤坏死因子α（TNF-α）、白细胞介素1（IL-1）、IL-6、IL-8、IL-10和IL-12。采用受试者工作特征（ROC）分析和主成分分析（PCA）来确定可识别细菌性脑膜炎的细胞因子组合。
纳入了684名6个月以下的婴儿；11名患有经培养证实的细菌性脑膜炎。IL-6和IL-10是在诊断经培养证实的细菌性脑膜炎中准确性最高的单个细胞因子（ROC分析；浓度-时间曲线下面积（AUC）分别为0.91；0.9103），其表现与使用ROC和PCA确定的组合相当或更好。在患有脑膜炎的婴儿中，CSF细胞因子彼此之间以及与CSF白细胞计数（WBC）高度相关。一部分接受抗生素预处理且培养结果为阴性的受试者表现出与培养结果为阳性的受试者相似的细胞因子模式。
CSF细胞因子水平可能有助于细菌性脑膜炎的诊断，并有助于对培养结果为阴性的脑膜炎的治疗决策。
