70例新生儿难治性化脓性脑膜炎临床特征分析

Clinical characteristics in 70 cases of neonatal refractory purulent meningitis

目的探讨新生儿难治性化脓性脑膜炎的临床特征,为指导临床实践提供参考。方法收集2017年1月至2020年6月成都市妇女儿童中心医院新生儿科收治的难治性新生儿化脓性脑膜炎病例的临床资料,进行回顾性研究。共诊断新生儿化脓性脑膜炎374例,其中72例为难治性新生儿化脓性脑膜炎;排除2例合并先天畸形者,最终纳入70例进行本研究。根据出生胎龄分为早产组(胎龄<37周)21例、足月组(胎龄≥37周)49例。比较两组患儿的临床资料(性别、胎龄、出生体质量、起病日龄、脑膜炎治疗时间、临床症状)、化验检查(血常规、病原菌培养、脑脊液常规和生化检查)、头颅磁共振成像(magnetic resonance imaging,MRI)结果。采用χ2检验、t检验、Mann-Whitney秩和检验进行统计分析。结果70例患儿平均治疗时间(33±12)d;中位发病日龄6.5(3.0,17.3)d,早产组发病日龄早于足月组[4.0(0.0,11.5)与8.0(4.5,18.0)d,Z=-2.314,P<0.05]。70例患儿中,发热、惊厥、呼吸道症状、休克分别有50例(71.4%)、4例(5.7%)、20例(28.6%)和3例(4.3%);足月组发热比例高于早产组[85.7%(42/49)与38.1%(8/21),χ2=16.333,P<0.05];早产组3例休克,足月组无休克病例;两组惊厥、出现呼吸道症状的比例差异均无统计学意义(P>0.05)。早产组血小板计数水平低于足月组[(205±179)×109与(300±165)×109/L,t=2.145,P<0.05],异常比例高于足月组[38.1%(8/21)与10.2%(5/49),χ2=5.830,P<0.05];两组白细胞计数及C-反应蛋白水平比较,差异无统计学意义(P>0.05)。早产组脑脊液中蛋白含量高于足月组[(2.17±1.03)与(1.57±1.01)g/L,t=2.238,P<0.05];糖含量低于足月组[1.73(0.85,2.50)与2.45(1.83,2.80)mmol/L,Z=-2.012,P<0.05]。两组脑脊液有核细胞数[332(106,2454)×106与226(77,553)×106/L]均显著高于正常范围。脑脊液培养阳性9例(12.9%),血培养阳性12例(17.1%);病原菌以大肠埃希菌及B族链球菌为主。头颅MRI检查74.3%(52/70)发现异常。87.1%(61/70)治愈,4.3%(3/70)好转,8.6%(6/70)中断治疗出院。结论新生儿化脓性脑膜炎临床症状不典型,对于发热的新生儿需警惕颅内感染可能。难治性病例中病原菌以大肠埃希菌及B族链球菌为主,需警惕耐药菌感染。

Objective To explore the clinical characteristics of refractory purulent meningitis in neonates,and provide clues for clinical management.Methods Clinical data of neonatal refractory purulent meningitis admitted from January 2017 to June 2020 were analyzed retrospectively.A total of 374 cases of neonatal purulent meningitis were diagnosed,of which 72 cases were refractory neonatal purulent meningitis.Two cases with congenital malformations were excluded,and 70 cases were included in this study.70 cases were divided into preterm group(gestational age<37 weeks,21 cases)and full-term group(gestational age≥37 weeks,49 cases)according to gestational age.The clinical characteristics(gender,gestational age,birth weight,age of onset,treatment duration,clinical symptoms),laboratory examination(routine blood test,pathogen culture,examination of cerebrospinal fluid),and results of magnetic resonance imaging(MRI)of two groups were compared.χ2 test,t-test,and Mann-Whitney test were used for statistical analysis.Results In the 70 cases,the average duration for meningitis therapy was(33±12)d,the median age of onset was 6.5(3.00,17.25)d,and the onset time in premature group was earlier than full-term group[4.0(0.0,11.5)vs 8.0(4.5,18.0)d,Z=-2.314,P<0.05].Among the 70 cases,50 cases(71.4%),4 cases(5.7%),20 cases(28.6%),and 3 cases(4.3%)had fever,convulsion,respiratory symptoms,and shock,respectively.The incidence of fever in full-term group was higher than that in preterm group[85.7%(42/49)vs 38.1%(8/21),χ2=16.333,P<0.05];there were 3 cases of shock in preterm group,but no shock in full-term group(P<0.05);there was no significant difference in the incidence of seizure and respiratory symptoms between the two groups(P>0.05).The average peripheral blood platelet count in preterm group was lower than that in term group[(205±179)×109 vs(300±165)×109/L,t=2.145,P<0.05],and the incidence of abnormal platelet count in preterm group was higher than that in full-term group[38.1%(8/21)vs 10.2%(5/49),χ2=5.830,P<0.05];while there was no significant difference in white blood cell count and C-reactive protein between the two groups(P>0.05).The preterm group had higher cerebrospinal fluid(CSF)protein than full-term group[(2.17±1.03)vs(1.57±1.01)g/L,t=2.238,P<0.05],while the CSF glucose was significantly lower than full-term group[1.73(0.85,2.50)vs 2.45(1.83,2.80)mmol/L,Z=-2.012,P<0.05].The number of nucleated cells in CSF of the two groups[332(106,2454)×106 and 226(77,553)×106/L]was significantly higher than the normal range.Among 70 cases,9 cases(12.9%)were positive in CSF culture and 12 cases(17.1%)were positive in blood culture.Escherichia coli and group B Streptococcus were the most common bacteria.Abnormal findings were found in 74.3%(52/70)of cranial MRI.The outcomes of these neonates were:87.1%(61/70)were cured,4.3%(3/70)improved,and 8.6%(6/70)discontinued treatment and discharged from hospital.Conclusions The clinical symptoms of neonatal purulent meningitis are not typical.It is necessary to be aware of intracranial infection if a neonate has fever.Escherichia coli and group B streptococcus are most common in refractory cases.In addition,we should be alert to drug-resistant bacterial infections.