新生儿难治性化脓性脑膜炎临床及影像学特点分析

Clinical and imaging characteristics in neonatal refractory purulent meningitis

目的：探讨新生儿难治性化脓性脑膜炎的临床及影像学特点。方法本研究为回顾性研究。收集2009年1月到2014年12月复旦大学附属儿科医院新生儿科收治的70例新生儿化脓性脑膜炎患儿的临床资料。根据所需抗感染治疗的疗程，分为难治组28例和普通组42例。分析新生儿难治性化脓性脑膜炎的临床和头颅MRI影像学特点。采用χ2检验、Fisher精确概率法、t检验或秩和检验进行统计学分析。将是否发生难治性化脓性脑膜炎作为因变量，结合新生儿的自身特点选取可能的影响因素进行分析。对单因素分析中有统计学意义的变量，采用Logistic回归分析进行变量筛选。结果70例患儿中，31例（44.3%）脑脊液和（或）血病原菌培养阳性。难治组病原菌以大肠埃希菌[8例（38.1%）]和B族链球菌[5例（23.8%）]为主，普通组病原菌以屎肠球菌为主（4例）。难治组与普通组比较，病程中惊厥发生率更高[53.6%（15/28）比7.1%（3/42），χ2=18.958，P＜0.01]，脑脊液白细胞数增多、蛋白含量增高、糖含量降低程度更显著[965.0（463.0~2200.0）×106/L 与116.5（61.0~327.5）×106/L，Z=－4.724；3221.1（2354.3~4633.5）与1487.6（988.2~1924.1）mg/L，Z=－4.669；0.2（0.1~0.8）与1.5（1.2~1.8）mmol/L，Z=－5.730；P值均＜0.01]，脑脊液/血病原学培养阳性率高[75%（21/28）比23.8%（10/42），χ2=17.843， P＜0.01]。Logistic回归分析表明，病程中出现惊厥、脑脊液糖含量降低、脑脊液或血液病原菌培养阳性提示易发展为新生儿难治性化脓性脑膜炎[OR值（95%CI）分别为9.6（1.2~76.0）、15.0（5.6~63.3）和7.3（1.5~36.0）]。与难治组头颅MRI异常发生率较普通组高[100.0%（28/28）与61.9%（26/42），χ2=13.827，P＜0.01]。难治组患儿头颅MRI更易出现脑外间隙异常[64.3%（18/28）与21.4%（9/42），χ2=13.023，P＜0.01]、脑室扩大[60.7%（17/28）与19.0%（8/42），χ2=12.704，P＜0.01]，脑室周围白质减少[28.6%（8/28）与2.4%（1/42），Fisher精确概率法， P=0.002]。难治组与普通组比较，住院时间长，近期不良预后发生率高[（48.0±17.4）与（26.0±10.2）d，t=6.016，P＜0.01；67.9%（19/28）与31.0%（13/42），χ2=9.220，P=0.002]，尤其为听力损害及需要神经外科干预的比例高[14/18耳与21.7%（10/46耳），χ2=4.292，P=0.038]。2组患儿住院期间均未发生感染相关死亡，在视觉损害及脑电图异常发生率差异无统计学意义，脑干诱发电位、视觉诱发电位以及脑电图检查时间差异亦均无统计学意义。结论新生儿化脓性脑膜炎病程中出现惊厥、脑脊液糖含量减低、脑脊液或血培养阳性提示可能发生新生儿难治性化脓性脑膜炎。难治性化脓性脑膜炎头颅MRI异常表现率高，尤其易出现脑外间隙异常、脑室扩大或脑室周围白质减少表现。

Objective To identify the clinical and imaging characteristics in neonatal refractory purulent meningitis. Methods Clinical data of 70 cases of neonatal purulent meningitis admitted to the neonatal intensive care unit at Children＆#39;s Hospital of Fudan University from January, 2009 to December, 2014 were reviewed retrospectively. The patients were divided into refractory group （n=28） and non-refractory group （n=42） according to the course of antimicrobial therapy.The clinical and brain MRI characteristics of neonatal refractory purulent meningitis were analyzed. Parameters were compared between the two groups using Chi-square or Fisher＆#39;s exact tests, and Wilcoxon tests where appropriate. Risk factors of neonatal refractory purulent meningitis were investigated by univariate and multivariate Logistic regression analysis. Results Among the 70 cases, 31（44.3%） were positive for cerebrospinal fluid （CSF）/blood culture. The positive rate was higher in the refractory group than in the non-refractory group [75.0%（21/28） vs 23.8%（10/42）,χ2=17.843, P〈0.01]. The most common pathogenic bacteria isolated in the refractory group were Escherichia coli [8 cases （38.1%）] and group B streptococci [5 cases （23.8%）]. Compared to the non-refractory group, patients in the refractory group were more likely to have seizure, higher CSF white blood cell count, higher CSF protein concentration and lower CSF glucose concentration [53.6%（15/28） vs 7.1% （3/42）, 965.0 （463.0-2 200.0）×106/L vs 116.5 （61.0-327.5）×106/L, 3 221.1（2 354.3-4 633.5） mg/L vs 1 487.6（988.2-1 924.1） mg/L, and 0.2 （0.1-0.8） mmol/L vs 1.5 （1.2-1.8） mmol/L; all P〈0.01]. Multivariate Logistic regression analysis showed that seizure, low CSF glucose concentration on admission, and a positive CSF/blood culture result neonatal refractory purulent meningitis （OR=9.6, 95%CI： 1.2-76.0; OR=15.0, 95%CI： 5.6-63.3; and OR=7.3, 95%CI： 1.5-36.0, respectively）. Abnormal brain MRI findings, including intracranial extracerebral space abnormality, ventricular dilatation and periventricular white matter injury, were more common in the refractory group [100.0%（28/28） vs 61.9%（26/42）, χ2=13.827 totally; 64.3%（18/28） vs 21.4%（9/42）, χ2=13.023 for intracranial extracerebral space abnormality; 60.7%（17/28） vs 19.0%（8/42）, χ2=12.704 for ventricular dilation and 28.6%（8/28） vs 2.4%（1/42） for periventricular white matter injury; all P 〈0.01]. Compared with the non-refractory group, the refractory group had a longer hospital stay [（48.0±17.4） d vs （26.0±10.2） d, t=6.016, P〈0.01] and more adverse events [67.9%（19/28） vs 31.0%（13/42）, χ2=9.220, P=0.002], including hearing impairment and requirement of neurosurgical intervention [14/18 ears vs 10/46 ears （21.7%）, χ2=4.292, P=0.038]. There was no death in both groups during hospitalization. Conclusions Neonates with seizure, low CSF glucose concentration and positive CSF/blood culture results are more likely to have refractory purulent meningitis. Brain MRI abnormalities are more common in neonatal refractory purulent meningitis.