儿童碳青霉烯类耐药肠杆菌目细菌感染的临床特征及分子流行研究

doi:10.7499/j.issn.1008-8830.2203145

摘要
图/表
参考文献(28)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (645 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的探讨儿童碳青霉烯类耐药肠杆菌目细菌（carbapenem-resistant Enterobacterales，CRE）感染的临床特征与分离株的分子特征。方法回顾性分析广东省人民医院2018年1月至2021年6月住院患儿的相关临床资料及感染情况，共获得非重复肠杆菌目细菌菌株1 098株。对所分离的66株CRE菌株进行药敏试验、PCR扩增和耐药相关基因测序，以研究分子流行情况。结果 1 098株肠杆菌目细菌中，CRE检出率为6.01%（66/1 098）。66株CRE来自66例患儿，其中男37例（56%），女29例（44%）；年龄2 d至14岁，其中<1月龄16例（24%），1月龄~ 28例（42%），12月龄~ 11例（17%），>36月龄11例（17%）。被检出CRE的患儿主要分布于新生儿科（38例，58%）、儿科重症监护室（17例，26%）等科室；呼吸道标本（48%）、中段尿标本（21%）、血液标本（17%）位于标本检出前3位。CRE菌株以肺炎克雷伯菌（45株，68%）、大肠埃希菌（12株，18%）、阴沟肠杆菌（6株，9%）为主，对亚胺培南和厄他培南等碳青霉烯类及青霉素头孢类高度耐药，对常见抗菌药物耐药性均普遍偏高，仅对阿米卡星（14%）、左旋氧氟沙星（23%）、妥布霉素（33%）等耐药率相对较低。肺炎克雷伯菌碳青霉烯酶基因型以bla_NDM（20株，44%）、bla_IMP（10株，22%）及bla_KPC（5株，11%）为主；大肠埃希菌碳青霉烯酶基因型以bla_NDM为主（10株，83%）；经测序，bla_NDM-1 24株，bla_NDM-5 6株，bla_IMP-4 5株，bla_KPC-2 3株，部分基因型尚未明确。结论儿童CRE感染发生率高，且集中于1~12月龄婴儿；CRE对抗菌药物的耐药性普遍偏高，儿童感染CRE菌株的碳青霉烯酶以金属酶为主。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	叶龙
	张莉滟
	赵越
	顾兵
	吴渚
	彭永正

关键词 ：碳青霉烯耐药肠杆菌目细菌, 耐药性, 分子流行病学, 儿童

Abstract：Objective To study the clinical features of children with carbapenem-resistant Enterobacterales (CRE) infection and the molecular characteristics of isolated strains. Methods A retrospective analysis was performed on the clinical data and infection status of the children who were hospitalized in Guangdong Provincial People's Hospital from January 2018 to June 2021. A total of 1 098 non-repetitive strains of Enterobacterales were obtained. Drug sensitivity test, PCR amplification, and resistance-related gene sequencing were performed for 66 isolated CRE strains to observe molecular epidemiology. Results Among the 1 098 strains of Enterobacterales, the detection rate of CRE was 6.01% (66/1 098). The 66 CRE strains were isolated from 66 children, among whom there were 37 boys (56%) and 29 girls (44%), with an age of 2 days to 14 years. Among these 66 children, 16 (24%) had an age of <1 month, 28 (42%) had an age of 1-12 months, 11 (17%) had an age of 12-36 months, and 11 (17%) had an age of >36 months. The children with CRE were mainly distributed in the department of neonatology (38 children, 58%) and the pediatric intensive care unit (17 children, 26%). The top three types of specimens with CRE detection were respiratory specimens (48%), midstream urine specimens (21%), and blood specimens (17%). The CRE strains were mainly Klebsiella pneumoniae (45 strains, 68%), Escherichia coli (12 strains, 18%), and Enterobacter cloacae (6 strains, 9%), with high resistance to carbapenems (such as imipenem and ertapenem), penicillin, and cephalosporins, slightly high resistance to commonly used antibiotics, and relatively low resistance to amikacin (14%), levofloxacin (23%), and tobramycin (33%). The carbapenemase genotypes of Klebsiella pneumoniae strains were mainly blaNDM (20 strains, 44%), blaIMP (10 strains, 22%), and blaKPC (5 strains, 11%), and the carbapenemase genotypes of Escherichia coli strains were mainly blaNDM (10 strains, 83%). After sequencing, there were 24 blaNDM-1 strains, 6 blaNDM-5 strains, 5 blaIMP-4 strains, and 3 blaKPC-2 strains, and some genotypes were not identified. Conclusions There is a high incidence rate of CRE infection among children, mainly those aged 1-12 months. CRE generally has high resistance to antibacterial drugs, and metalloenzymes are the main type of carbapenemases for CRE strains in children.

Key words： Carbapenem-resistant Enterobacterales Drug resistance Molecular epidemiology Child

收稿日期: 2022-03-25

基金资助:国家自然科学基金（81871734；82072380）；广东省基础与应用基础研究基金（2021A1515220022）。

通讯作者: 彭永正，男，主任技师。Email：yzpeng1981@126.com。 E-mail: yzpeng1981@126.com

作者简介: 叶龙，男，硕士研究生，技；

引用本文:

叶龙,张莉滟,赵越等. 儿童碳青霉烯类耐药肠杆菌目细菌感染的临床特征及分子流行研究[J]. 中国当代儿科杂志, 2022, 24(8): 881-886.

YE Long,ZHANG Li-Yan,ZHAO Yue et al. Clinical features and molecular epidemiology of carbapenem-resistant Enterobacterales infection in children[J]. CJCP, 2022, 24(8): 881-886.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2203145 或 http://www.zgddek.com/CN/Y2022/V24/I8/881

	Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae[J]. Emerg Infect Dis, 2011, 17(10): 1791-1798. PMID: 22000347. PMCID: PMC3310682. DOI: 10.3201/eid1710.110655.
	Brennan-Krohn T, Manetsch R, O'Doherty GA, et al. New strategies and structural considerations in development of therapeutics for carbapenem-resistant Enterobacteriaceae[J]. Transl Res, 2020, 220: 14-32. PMID: 32201344. PMCID: PMC7293954. DOI: 10.1016/j.trsl.2020.02.008.
	Chiotos K, Hayes M, Gerber JS, et al. Treatment of carbapenem-resistant Enterobacteriaceae infections in children[J]. J Pediatric Infect Dis Soc, 2020, 9(1): 56-66. PMID: 31872226. PMCID: PMC7047006. DOI: 10.1093/jpids/piz085.
	4 付盼, 王传清, 俞蕙, 等. 中国儿童细菌耐药监测组2018年儿童细菌感染及耐药监测[J]. 中国循证儿科杂志, 2019, 14(5): 321-326. DOI: 10.3969/j.issn.1673-5501.2019.05.001.
	5 尚红, 王毓三, 申子瑜, 等. 全国临床检验操作规程[M]. 4版. 北京: 人民卫生出版社, 2015.
	6 Clinical and Laboratory Standards Institute. M100: performance standards for antimicrobial susceptibility testing, 32nd edition[EB/OL]. [2022-06-07]. https://www.clsi.org/standards/products/microbiology/documents/m100/.
	Cornaglia G, Giamarellou H, Rossolini GM. Metallo-β-lactamases: a last frontier for β-lactams?[J]. Lancet Infect Dis, 2011, 11(5): 381-393. PMID: 21530894. DOI: 10.1016/S1473-3099(11)70056-1.
	Dallenne C, Da Costa A, Decré D, et al. Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae[J]. J Antimicrob Chemother, 2010, 65(3): 490-495. PMID: 20071363. DOI: 10.1093/jac/dkp498.
	9 胡付品. CHINET中国细菌耐药监测结果: (2021年1-12月)[EB/OL]. [2022-06-07]. https://www.chinets.com/Document.
	10 杨欣, 鲁利群, 黄莉, 等. 儿科碳青霉烯类耐药肺炎克雷伯菌感染危险因素及其耐药性[J]. 中华医院感染学杂志, 2020, 30(22): 3470-3473. DOI: 10.11816/cn.ni.2020-206730.
	11 全国细菌耐药监测网. 2020年全国细菌耐药监测报告[J]. 中华检验医学杂志, 2022, 45(2): 122-136. DOI: 10.3760/cma.j.cn114452-20211118-00721.
	Mrowiec P, Klesiewicz K, Ma?ek M, et al. Antimicrobial susceptibility and prevalence of extended-spectrum beta-lactamases in clinical strains of Klebsiella pneumoniae isolated from pediatric and adult patients of two Polish hospitals[J]. New Microbiol, 2019, 42(4): 197-204. PMID: 31609454.
	13 何磊燕, 付盼, 吴霞, 等. 中国儿童细菌耐药监测组2020年儿童细菌耐药监测[J]. 中国循证儿科杂志, 2021, 16(6): 414-420. DOI: 10.3969/j.issn.1673-5501.2021.06.002.
	14 付盼, 何磊燕, 王传清, 等. 中国儿童细菌耐药监测组2019年儿童细菌耐药监测[J]. 中国循证儿科杂志, 2021, 16(1): 43-49. DOI: 10.3969/j.issn.1673-5501.2021.01.002.
	15 胡付品, 郭燕, 朱德妹, 等. 2020年CHINET中国细菌耐药监测[J]. 中国感染与化疗杂志, 2021, 21(4): 377-387. DOI: 10.16718/j.1009-7708.2021.04.001.
	16 胡付品, 郭燕, 朱德妹, 等. 2019年CHINET三级医院细菌耐药监测[J]. 中国感染与化疗杂志, 2020, 20(3): 233-243. DOI: 10.16718/j.1009-7708.2020.03.001.
	Yin L, He L, Miao J, et al. Carbapenem-resistant Enterobacterales colonization and subsequent infection in a neonatal intensive care unit in Shanghai, China[J]. Infect Prev Pract, 2021, 3(3): 100147. PMID: 34647006. PMCID: PMC8498732. DOI: 10.1016/j.infpip.2021.100147.
	Flannery DD, Chiotos K, Gerber JS, et al. Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management[J]. Pediatr Res, 2022, 91(2): 380-391. PMID: 34599280. PMCID: PMC8819496. DOI: 10.1038/s41390-021-01745-7.
	Rozaidi SW, Sukro J, Dan A. The incidence of nosocomial infection in the Intensive Care Unit, Hospital Universiti Kebangsaan Malaysia: ICU-acquired nosocomial infection surveillance program 1998-1999[J]. Med J Malaysia, 2001, 56(2): 207-222. PMID: 11771082.
	Little ML, Qin X, Zerr DM, et al. Molecular diversity in mechanisms of carbapenem resistance in paediatric Enterobacteriaceae[J]. Int J Antimicrob Agents, 2012, 39(1): 52-57. PMID: 22055532. PMCID: PMC3237943. DOI: 10.1016/j.ijantimicag.2011.09.014.
	Wu W, Feng Y, Tang G, et al. NDM metallo-β-lactamases and their bacterial producers in health care settings[J]. Clin Microbiol Rev, 2019, 32(2): e00115-18. PMID: 30700432. PMCID: PMC6431124. DOI: 10.1128/CMR.00115-18.
	Khan AU, Maryam L, Zarrilli R. Structure, genetics and worldwide spread of New Delhi metallo-β-lactamase (NDM): a threat to public health[J]. BMC Microbiol, 2017, 17(1): 101. PMID: 28449650. PMCID: PMC5408368. DOI: 10.1186/s12866-017-1012-8.
	Dong F, Zhang Y, Yao K, et al. Epidemiology of carbapenem-resistant Klebsiella pneumoniae bloodstream infections in a Chinese children's hospital: predominance of New Delhi metallo-β-lactamase-1[J]. Microb Drug Resist, 2018, 24(2): 154-160. PMID: 28594635. DOI: 10.1089/mdr.2017.0031.
	Zhang X, Chen D, Xu G, et al. Molecular epidemiology and drug resistant mechanism in carbapenem-resistant Klebsiella pneumoniae isolated from pediatric patients in Shanghai, China[J]. PLoS One, 2018, 13(3): e0194000. PMID: 29558475. PMCID: PMC5860732. DOI: 10.1371/journal.pone.0194000.
	25 廖兰凯, 廖雪莲, 康焰. 耐碳青霉烯类肠杆菌防控现状及研究进展[J]. 中华医院感染学杂志, 2019, 29(11): 1750-1755. DOI: 10.11816/cn.ni.2019-186124.
	Fritzenwanker M, Imirzalioglu C, Herold S, et al. Treatment options for carbapenem-resistant gram-negative infections[J]. Dtsch Arztebl Int, 2018, 115(20-21): 345-352. PMID: 29914612. PMCID: PMC6172649. DOI: 10.3238/arztebl.2018.0345.
	Alatoom A, Elsayed H, Lawlor K, et al. Comparison of antimicrobial activity between ceftolozane-tazobactam and ceftazidime-avibactam against multidrug-resistant isolates of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa[J]. Int J Infect Dis, 2017, 62: 39-43. PMID: 28610832. DOI: 10.1016/j.ijid.2017.06.007.
	28 余佳佳, 刘婧娴, 李媛睿, 等. 利用MALDI-TOF MS特异质量峰对耐碳青霉烯类肺炎克雷伯菌同源性的快速分型[J]. 中国感染控制杂志, 2019, 18(3): 206-212. DOI: 10.12138/j.issn.1671-9638.20193912.