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

Clinical features and molecular epidemiology of carbapenem-resistant Enterobacterales infection in children

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。

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.