有并发症的产单核细胞李斯特菌脑膜炎三例临床特点与二代测序结果分析  

Clinical characteristics and next generation sequencing of three cases of Listeria monocytogenes meningitis with complications

作　　者：李牧寒 李永军 胡冰[1] 郭凌云[1] 郭欣[1] 关鸿志[3] 张建昭[4] 刘钢[1] Li Muhan;Li Yongjun;Hu Bing;Guo Lingyun;Guo Xin;Guan Hongzhi;Zhang Jianzhao;Liu Gang(Department of Infectious Diseases, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing 100045, China;Shenzhen Huada Gene Research Institute, Shenzhen 518083, China;Department of Neurology, Chinese Academy of Medical Sciences, Peking Union Medical College, Peking Union Medical College Hospital, Beijing 100730, China;Department of Neurology, Children′s Hospital Affiliated to Capital Institute of Pediatrics, Beijing 100020, China)

机构地区：[1]国家儿童医学中心,首都医科大学附属北京儿童医院感染内科,儿科重大疾病研究教育部重点实验室,100045 [2]深圳华大基因研究院,518083 [3]中国医学科学院,北京协和医学院,北京协和医院神经科,100730 [4]首都儿科研究所附属儿童医院神经内科,北京100020

出　　处：《中华儿科杂志》2019年第8期603-606,607,共5页Chinese Journal of Pediatrics

基　　金：北京市医院管理中心儿科学科协同发展中心专项经费(XTZD20180501);北京市医院管理局"登峰"人才培养计划(DFL20181201).

摘　　要：目的总结分析有并发症的产单核细胞李斯特菌脑膜炎(LMM)的临床特点及二代测序结果。方法对2015年7月至2017年11月在首都医科大学附属北京儿童医院感染内科诊断为LMM的3例患儿临床特点、实验室检查、影像学特征、药物治疗、脑脊液二代测序情况进行回顾性分析。结果3例患儿分别为1岁女童、2岁女童、9岁男童,免疫功能均正常,发病前食用过冰箱冷藏食物或牛奶或奶制品。症状有发热、头痛、腹痛、腹泻、呕吐、抽搐等。例1合并败血症、肺炎,例2、3患儿分别于病初和病程中分别诊断为阑尾炎和美克尔憩室炎。3例患儿脑脊液白细胞数均升高,头颅磁共振成像显示脑膜或脑室周围受累。患儿均由脑脊液培养阳性结果确诊,脑脊液二代测序送检时间较晚,送检时均应用碳青霉烯类抗菌药物,但均显示了阳性结果,比传统培养分别提前2、2、9 d回报。基因覆盖度分别为5.00%、7.00%、0.04%,序列数分别为2 561、1 011、8。3例患儿病初应用头孢类抗菌药物经验性治疗仍然反复高热,相关实验室指标进一步升高,应用碳青霉烯类抗菌药物治疗后最终好转出院。结论LMM可发生于免疫功能正常儿童,易合并存在消化系统症状,脑脊液病原二代测序技术可以快速、准确地检测脑脊液中的产单核细胞李斯特菌,同时不受限于采样时间以及抗菌药物的应用。Objective To summarize the clinical characteristics of Listeria monocytogenes meningitis (LMM) with complications, and analyze the outcomes of next generation sequencing. Methods Clinical characteristics, laboratory findings, imaging features, antibiotics treatment, and next generation sequencing of cerebrospinal fluid were analyzed in 3 LMM patients who were hospitalized in the Department of Infectious Diseases of Beijing Children′s Hospital Affiliated to Capital Medical University from July 2015 to November 2017. Results The three patients were 1-year-old girl, 2-year-old girl, and 9-year-old boy, with normal immune function. They had eaten refrigerated food, milk or dairy products before onset. Symptoms included fever, headache, abdominal pain, diarrhea, vomiting, and convulsions, etc. The complications of two cases (case 2 and 3) were appendicitis and Meckel′s diverticulitis. The other one (case 1) was with sepsis and pneumonia. Leukocyte counts in cerebrospinal fluid were elevated in all the three cases, and cranial magnetic resonance imaging showed meningeal or periventricular involvement. All the children were diagnosed with LMM by positive CSF culture. CSF for next generation sequencing was sent after carbapenem antibiotics using, yet all the results were positive. The positive results were returned 2, 9, and 9 days earlier than culture results, respectively. The gene coverage was 5.00%, 7.00%, 0.04%, and the reads was 2 561, 1 011 and 8, respectively. All the three children had recurrent fever despite using cephalosporin. Levels of leukocytes in the blood and CSF further elevated. After using carbapenem antibiotics, patients improved eventually and were discharged from hospital. Conclusions LMM can occur in children with normal immune function and is usually associated with digestive system symptoms. Listeria monocytogenes can be detected quickly and accurately by the next generation sequencing technology, without being limited to sampling time and antibiotics application.

关 键 词：儿童 脑膜炎 利斯特菌性 新一代测序技术 

分 类 号：R72[医药卫生—儿科] R742[医药卫生—临床医学]