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儿童肺炎链球菌脑膜炎临床特征及药物敏感性单中心临床研究
作者姓名:朱亮  郭欣  王曦  窦珍珍  姚开虎  史伟  刘钢
作者单位:国家儿童医学中心;国家儿童医学中心
基金项目:福棠儿童科学基金项目(FTCSF-2018-01);北京市医院管理中心儿科学科协同发展中心专项经费(XTZD20180501);北京市医院管理中心"登峰"人才培养计划团队(DFL20181201)。
摘    要:目的:了解儿童肺炎链球菌脑膜炎(PM)的临床特点、细菌耐药情况及部分菌株的血清型情况。方法:回顾性分析2012年1月至2017年12月首都医科大学附属北京儿童医院住院PM患儿72例的临床资料、随访结果、分离菌株药物敏感性及血清型分型结果,分析PM死亡的危险因素。结果:72例患儿中男46例,女26例;年龄1个月~9岁;住院天数1~363 d,中位数22.0 d。社区获得性感染71例(98.6%)。有明确基础疾病患儿28例(38.9%),其中前3位为脑脊液鼻漏(6例)、头外伤(4例)和免疫缺陷病(4例)。临床症状以发热为最常见(72例,100.0%),其次为精神萎靡(60例,83.3%)、意识改变(46例,63.9%)、呕吐(45例,62.5%)、抽搐(42例,58.3%)、前囟张力增高(27例,37.5%)及头痛(17例,23.6%)等。神经系统并发症44例(61.1%),以硬膜下积液最多见29例(40.3%)]。再发细菌性脑膜炎2例,均为反复肺炎链球菌感染。脑膜炎和脑膜脑炎占比分别为43.1%(31/72例)和56.9%(41/72例)。脑膜炎菌株对青霉素的不敏感率为74.3%,对红霉素、克林霉素、四环素的耐药率分别为95.7%、95.7%、89.1%;对左氧氟沙星、万古霉素、利奈唑胺均敏感。24例(33.3%)患儿有菌株分型结果,其中19F型8株(33.4%),14型5株,23F型4株,6A型3株,19A型2株,1型和15B型各1株。13价肺炎链球菌结合疫苗(PCV13)覆盖率达95.8%(23/24株)。随访72例,其中好转51例,死亡21例(病死率为29.2%),遗留后遗症患儿21例(29.2%)。多变量Logistic回归分析显示,呼吸衰竭和外周血白细胞数<4×10^9/L为PM患儿死亡的独立危险因素(均P<0.05)。结论:本中心儿童PM病例多发生于5岁以下,脑脊液鼻漏、头外伤和免疫缺陷病是儿童PM常见的基础疾病,病程中有呼吸衰竭或外周血白细胞数减少者可能提示预后不良。

关 键 词:肺炎球菌感染  脑膜炎  儿童

Single center clinical study on clinical characteristics and drug susceptibility of pneumococcal meningitis in children
Authors:Zhu Liang  Guo Xin  Wang Xi  Dou Zhenzhen  Yao Kaihu  Shi Wei  Liu Gang
Institution:(Key Laboratory for Major Disease in Children,Ministry of Education,Department of Infectious Diseases,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China;Key Laboratory of Major Diseases in Children,Ministry of Education,National Key Discipline of Pediatrics(Capital Medical University),Beijing Pediatric Research Institute,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China)
Abstract:Objective To explore the clinical characteristics,drug resistance and the serotype distribution of the isolates from peadiatric patients with pneumococcal meningitis(PM).Methods Clinical data,follow-up outcomes,drug susceptibility of isolated strains and serotyping results of 72 children diagnosed as PM and hospitalized in Beijing Children′s Hospital,Capital Medical University,from January 2012 to December 2017 were retrospectively analyzed,and the independent risk factors of mortality in the PM patients were analyzed.Results There were 46 males and 26 females.In 72 PM cases,with the age ranging from 1 month to 9 years,and hospital stay from 1 to 363 days(median,22.0 d).A total of 71 cases(98.6%)had community-acquired infections.There were 28 cases(38.9%)with definite underlying diseases,the top 3 of which were cerebrospinal fluid rhinorrhea(6 cases),head trauma(4 cases)and immunodeficiency diseases(4 cases).Fever(72 cases,100.0%)was the most common clinical symptom,followed by depression of spirit,change of consciousness(46 cases,63.9%),vomitting(45 cases,62.5%),convulsion(42 cases,58.3%),increased tension of anterior fontanelle(27 cases,37.5%)and headache(17 cases,23.6%).There were 44 cases(61.1%)of neurological complications,including 29 cases(40.3%)of subdural effusion.Bacterial meningitis recurred in 2 cases,both of which were recurrent Streptococcus pneumoniae infection.The intracranial infections were divided into meningitis(43.1%,31/72 cases)and meningoencephalitis(56.9%,41/72 cases).The penicillin nonsensitive rate of meningitis isolates was 74.3%,and their resistance rate to Erythromycin,Clindamycin and Tetracycline were 95.7%,95.7%and 89.1%,respectively.All meningitis isolates were susceptible to Levofloxacin,Vancomycin and Linezolid.The serotypes of 24 cases(33.3%)were identified,among which 8 strains were type 19F(33.4%),5 strains were type 14,4 strains were type 23F,3 strains were type 6A,2 strains were type 19A,1 strain was type 1 and 1 strain was type 15B,with a 13-valent protein-polysaccharide conjugate vaccine(PCV13)coverage rate of 95.8%(23/24 strains).Among all children that were followed up,51 cases got better,21 cases(case fatality rate was 29.2%)were confirmed dead,and 21 children(29.2%)had sequelae.The multiva-riate Logistic regression analysis suggested that respiratory failure and peripheral blood white blood cell count<4×10^9/L were independent risk factors for death of children with PM(all P<0.05).Conclusions Most PM cases in this center are children under 5 years old.Cerebrospinal fluid rhinorrhea,head trauma and immunodeficiency diseases are common underlying diseases in children with PM.Respiratory failure or peripheral blood leukopenia during the course of the disease may indicate a poor prognosis.
Keywords:Pneumococcal infections  Meningitis  Child
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