2019—2020年160例儿童肺炎链球菌脑膜炎临床流行病学多中心研究

王彩云; 许红梅; 刘钢; 刘静; 俞蕙; 陈必全; 郑帼; 舒敏; 杜丽君; 徐志伟; 黄丽素; 李海波; 汪东; 白松婷; 单庆文; 朱春晖; 田健美; 郝建华; 林爱伟; 林道炯; 吴谨准; 张新华; 曹清; 陶仲宾; 陈源; 朱国龙; 薛萍; 汤正珍; 苏学文; 曲政海; 赵仕勇; 庞琳; 邓慧玲; 舒赛男; 陈英虎

doi:10.7499/j.issn.1008-8830.2308090

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中国当代儿科杂志 ›› 2024, Vol. 26 ›› Issue (2) : 131-138. DOI: 10.7499/j.issn.1008-8830.2308090

论著·临床研究

2019—2020年160例儿童肺炎链球菌脑膜炎临床流行病学多中心研究

王彩云¹, 许红梅², 刘钢³, 刘静⁴, 俞蕙⁵, 陈必全⁶, 郑帼⁷, 舒敏⁸, 杜丽君⁹, 徐志伟¹⁰, 黄丽素¹¹, 李海波¹², 汪东¹³, 白松婷¹⁴, 单庆文¹⁵, 朱春晖¹⁶, 田健美¹⁷, 郝建华¹⁸, 林爱伟¹⁹, 林道炯²⁰, 吴谨准²¹, 张新华²², 曹清²³, 陶仲宾²⁴, 陈源²⁵, 朱国龙²⁶, 薛萍²⁷, 汤正珍²⁸, 苏学文²⁹, 曲政海³⁰, 赵仕勇³¹, 庞琳³², 邓慧玲³³, 舒赛男³⁴, 陈英虎¹

作者信息 +

1.浙江大学医学院附属儿童医院感染科，浙江杭州 310052
2.重庆医科大学附属儿童医院感染科，重庆 400014
3.首都医科大学附属北京儿童医院感染科，北京 100045
4.湖南省儿童医院感染科，湖南长沙 410007
5.复旦大学附属儿科医院感染科，上海 201102
6.安徽省儿童医院感染科，安徽合肥 230022
7.南京医科大学附属儿童医院神经科，江苏南京 210008
8.四川大学华西第二医院儿科，四川成都 610044
9.山西省儿童医院神经内科，山西太原 030006
10.温州医科大学附属第二医院/ 育英儿童医院普儿科，浙江温州 325027
11.上海交通大学医学院附属新华医院感染科，上海 200092
12.吉林大学第一医院儿科门诊，吉林长春 130061
13.西安交通大学附属儿童医院，陕西西安 710002
14.郑州大学第一附属医院儿科，河南郑州 450052
15.广西医科大学第一附属医院儿科，广西南宁 530021
16.江西省儿童医院感染科，江西南昌 330006
17.苏州大学附属儿童医院感染科，江苏苏州 215002
18.河南开封市儿童医院感染科，河南开封 475000
19.山东大学儿童院感染科，山东济南 250022
20.海南省妇幼保健院感染科，海南海口 571103
21.厦门大学附属妇女儿童医院儿科，福建厦门 361003
22.山西省儿童医院新生儿科，山西太原 030006
23.上海交通大学医学院附属上海儿童医学中心感染科，上海 200127
24.兰州大学第一医院儿科，甘肃兰州 730013
25.河北医科大学第二医院儿科，河北石家庄 050004
26.青海省妇女儿童医院感染消化科，青海西宁 810007
27.太原市妇幼保健院儿内科，山西太原 030012
28.遵义市第一人民医院儿科，贵州遵义 563099
29.内蒙古自治区人民医院儿科，内蒙古呼和浩特 750306
30.青岛大学附属医院儿科，山东青岛 266003
31.杭州市儿童医院感染科，浙江杭州 310005
32.首都医科大学附属北京地坛医院儿科，北京 100102
33.西安市中心医院儿科，陕西西安 710004
34.华中科技大学同济医学院附属同济医院儿科，湖北武汉 430030

作者简介:

王彩云，女，硕士，副主任医师；

折叠

A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020

WANG Cai-Yun, XU Hong-Mei, LIU Gang, LIU Jing, YU Hui, CHEN Bi-Quan, ZHENG Guo, SHU Min, DU Li-Jun, XU Zhi-Wei, HUANG Li-Su, LI Hai-Bo, WANG Dong, BAI Song-Ting, SHAN Qing-Wen, ZHU Chun-Hui, TIAN Jian-Mei, HAO Jian-Hua, LIN Ai-Wei, LIN Dao-Jiong, WU Jin-Zhun, ZHANG Xin-Hua, CAO Qing, TAO Zhong-Bin, CHEN Yuan, ZHU Guo-Long, XUE Ping, TANG Zheng-Zhen, SU Xue-Wen, QU Zheng-Hai, ZHAO Shi-Yong, PANG Lin, DENG Hui-Ling, SHU Sai-Nan, CHEN Ying-Hu

Author information +

文章历史 +

摘要

目的研究中国儿童肺炎链球菌脑膜炎（pneumococcal meningitis, PM）的临床特征、转归和分离菌株肺炎链球菌（Streptococcus pneumoniae, SP）的药物敏感性。方法回顾性分析2019年1月—2020年12月全国33家三级甲等医院160例<15岁的PM住院患儿的临床信息、实验室资料和微生物学资料。结果 160例PM患儿中，男103例，女57例；年龄15 d至15岁，其中3月龄至<3岁109例（68.1%）。脑脊液培养分离SP菌株95例（59.4%），血培养分离SP菌株57例（35.6%）。脑脊液宏基因组二代测序和脑脊液SP抗原检测阳性率分别为40%（35/87）、27%（21/78）。55例（34.4%）患儿存在1个或多个化脓性脑膜炎高危因素；113例（70.6%）患儿有1个或多个颅外感染病灶；18例（11.3%）有明确基础疾病。临床症状以发热最常见（147例，91.9%），其次是精神萎靡（98例，61.3%）、呕吐（61例，38.1%）等。69例（43.1%）患儿住院期间发生颅内并发症，常见并发症为硬膜下积液和/或积脓（43例，26.9%）、脑积水（24例，15.0%）、脑脓肿（23例，14.4%）、脑出血（8例，5.0%）。硬膜下积液和/或积脓和脑积水主要发生在<1岁患儿，分别为91%（39/43）、83%（20/24）。SP菌株对万古霉素（100%，75/75）、利奈唑胺（100%，56/56）、厄他培南（100%，6/6）完全敏感；对左氧氟沙星（81%，22/27）、莫西沙星（82%，14/17）、利福平（96%，25/26）和氯霉素（91%，21/23）敏感率高；对青霉素（16%，11/68）、克林霉素（6%，1/17）敏感率低；对红霉素完全耐药（100%，31/31）。痊愈和好转出院率分别为22.5%（36/160）、66.2%（106/160）；18例（11.3%）出现不良结局。结论儿童PM多见于3月龄至<3岁婴幼儿，颅内并发症多发生在<1岁患儿，发热是PM患儿最常见的临床表现，硬膜下积液和/或积脓、脑积水是最常见的并发症。脑脊液非培养检测方法有助于提高病原菌检出率。超过10% PM患儿出现不良结局。SP菌株对万古霉素、利奈唑胺、厄他培南、左氧氟沙星、莫西沙星、利福平、氯霉素敏感率高。

Abstract

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. Methods A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. Results Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. Conclusions Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

导出引用

王彩云, 许红梅, 刘钢, 刘静, 俞蕙, 陈必全, 郑帼, 舒敏, 杜丽君, 徐志伟, 黄丽素, 李海波, 汪东, 白松婷, 单庆文, 朱春晖, 田健美, 郝建华, 林爱伟, 林道炯, 吴谨准, 张新华, 曹清, 陶仲宾, 陈源, 朱国龙, 薛萍, 汤正珍, 苏学文, 曲政海, 赵仕勇, 庞琳, 邓慧玲, 舒赛男, 陈英虎. 2019—2020年160例儿童肺炎链球菌脑膜炎临床流行病学多中心研究[J]. 中国当代儿科杂志. 2024, 26(2): 131-138 https://doi.org/10.7499/j.issn.1008-8830.2308090

WANG Cai-Yun, XU Hong-Mei, LIU Gang, LIU Jing, YU Hui, CHEN Bi-Quan, ZHENG Guo, SHU Min, DU Li-Jun, XU Zhi-Wei, HUANG Li-Su, LI Hai-Bo, WANG Dong, BAI Song-Ting, SHAN Qing-Wen, ZHU Chun-Hui, TIAN Jian-Mei, HAO Jian-Hua, LIN Ai-Wei, LIN Dao-Jiong, WU Jin-Zhun, ZHANG Xin-Hua, CAO Qing, TAO Zhong-Bin, CHEN Yuan, ZHU Guo-Long, XUE Ping, TANG Zheng-Zhen, SU Xue-Wen, QU Zheng-Hai, ZHAO Shi-Yong, PANG Lin, DENG Hui-Ling, SHU Sai-Nan, CHEN Ying-Hu. A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(2): 131-138 https://doi.org/10.7499/j.issn.1008-8830.2308090

参考文献

1 Guo LY, Zhang ZX, Wang X, et al. Clinical and pathogenic analysis of 507 children with bacterial meningitis in Beijing, 2010-2014[J]. Int J Infect Dis, 2016, 50: 38-43. PMID: 27452172. DOI: 10.1016/j.ijid.2016.07.010.
2 Li C, Feng WY, Lin AW, et al. Clinical characteristics and etiology of bacterial meningitis in Chinese children >28 days of age, January 2014–December 2016: a multicenter retrospective study[J]. Int J Infect Dis, 2018, 74: 47-53. PMID: 30100536. DOI: 10.1016/j.ijid.2018.06.023.
3 World Health Organization. Pneumococcal conjugate vaccines in infants and children under 5 years of age: WHO position paper—February 2019[J]. Wkly Epidemiol Rec, 2019, 94(8): 85-103.
4 World Health Organization. Immunization coverage[EB/OL]. (2023-07-18)[2022-12-10]. https://www.who.int/news-room/fact-sheets/detail/immunization-coverage.
5 GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the global burden of disease study 2016[J]. Lancet, 2017, 390(10100): 1151-1210. PMID: 28919116. PMCID: PMC5605883. DOI: 10.1016/S0140-6736(17)32152-9.
6 Hénaff F, Levy C, Cohen R, et al. Risk factors in children older than 5 years with pneumococcal meningitis: data from a national network[J]. Pediatr Infect Dis J, 2017, 36(5): 457-461. PMID: 28403047. DOI: 10.1097/INF.0000000000001470.
7 GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the global burden of disease study 2016[J]. Lancet Neurol, 2019, 18(5): 459-480. PMID: 30879893. PMCID: PMC6459001. DOI: 10.1016/S1474-4422(18)30499-X.
8 GBD 2016 Brain and Other CNS Cancer Collaborators. Global, regional, and national burden of brain and other CNS cancer, 1990-2016: a systematic analysis for the global burden of disease study 2016[J]. Lancet Neurol, 2019, 18(4): 376-393. PMID: 30797715. PMCID: PMC6416167. DOI: 10.1016/S1474-4422(18)30468-X.
9 Collaborators G2M. Global, regional, and national burden of meningitis, 1990-2016: a systematic analysis for the global burden of disease study 2016[J]. Lancet Neurol, 2018, 17(12): 1061-1082. PMID: 30507391. PMCID: PMC6234314. DOI: 10.1016/S1474-4422(18)30387-9.
10 王天有, 申昆玲, 沈颖. 诸福棠实用儿科学[M]. 9版. 北京: 人民卫生出版社, 2022: 1077-1100.
11 van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis[J]. Clin Microbiol Infect, 2016, 22 (Suppl 3): S37-S62. PMID: 27062097. DOI: 10.1016/j.cmi.2016.01.007.
12 曹云, 程国强, 侯新琳, 等. 新生儿细菌性脑膜炎病因、诊断与治疗[J]. 中华围产医学杂志, 2016, 19(12): 881-884. DOI: 10.3760/cma.j.issn.1007-9408.2016.12.001.
13 中华医学会儿科学分会感染学组, 《中华儿科杂志》编辑委员会. 儿童肺炎链球菌性疾病诊治与防控建议[J]. 中华儿科杂志, 2018, 56(8): 564-570. PMID: 30078235. DOI: 10.3760/cma.j.issn.0578-1310.2018.08.002.
14 中华医学会神经病学分会感染性疾病与脑脊液细胞学学组. 中枢神经系统感染性疾病的脑脊液宏基因组学第二代测序应用专家共识[J]. 中华神经科杂志, 2021, 54(12): 1234-1240. DOI: 10.3760/cma.j.cn113694-20210730-00532.
15 王彩云, 许红梅, 田姣, 等. 儿童急性细菌性脑膜炎多中心流行病学研究[J]. 中华儿科杂志, 2022, 60(10): 1045-1053. PMID: 36207852. DOI: 10.3760/cma.j.cn112140-20220608-00522.
16 WHO Publication. Pneumococcal vaccines WHO position paper:2012—recommendations[J]. Vaccine, 2012, 30(32): 4717-4718. PMID: 22621828. DOI: 10.1016/j.vaccine.2012.04.093.
17 方潮, 陈学军, 周明明, 等. 2016年九家儿童医院肺炎链球菌感染的临床特征及分离株药物敏感性分析[J]. 中华儿科杂志, 2018, 56(8): 582-586. PMID: 30078238. DOI: 10.3760/cma.j.issn.0578-1310.2018.08.005.
18 Ampofo K, Bender J, Sheng X, et al. Seasonal invasive pneumococcal disease in children: role of preceding respiratory viral infection[J]. Pediatrics, 2008, 122(2): 229-237. PMID: 18676537. DOI: 10.1542/peds.2007-3192.
19 Fricke LM, Gl?ckner S, Dreier M, et al. Impact of non-pharmaceutical interventions targeted at COVID-19 pandemic on influenza burden: a systematic review[J]. J Infect, 2021, 82(1): 1-35. PMID: 33278399. PMCID: PMC9183207. DOI: 10.1016/j.jinf.2020.11.039.
20 王彩云, 许红梅, 邓继岿, 等. 儿童肺炎链球菌脑膜炎临床特征及药物敏感性多中心临床研究[J]. 中华儿科杂志, 2019, 57(5): 355-362. PMID: 31060128. DOI: 10.3760/cma.j.issn.0578-1310.2019.05.008.
21 中华医学会儿科学分会神经学组. 儿童社区获得性细菌性脑膜炎诊断与治疗专家共识[J]. 中华儿科杂志, 2019, 57(8): 584-591. PMID: 31352742. DOI: 10.3760/cma.j.issn.0578-1310.2019.08.003.
22 Wilson MR, Sample HA, Zorn KC, et al. Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis[J]. N Engl J Med, 2019, 380(24): 2327-2340. PMID: 31189036. PMCID: PMC6764751. DOI: 10.1056/NEJMoa1803396.