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

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1098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1098株肠杆菌目细菌中,CRE检出率为6.01%(66/1098)。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。[中国当代儿科杂志,2022,24(8):881-886]

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 1098 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 1098 strains of Enterobacterales,the detection rate of CRE was 6.01%(66/1098).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 bla_(NDM)(20 strains,44%),bla_(IMP)(10 strains,22%),and bla_(KPC)(5 strains,11%),and the carbapenemase genotypes of Escherichia coli strains were mainly bla_(NDM)(10 strains,83%).After sequencing,there were 24 bla_(NDM-1) strains,6 bla_(NDM-5) strains,5 bla_(IMP-4) strains,and 3 bla_(KPC-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.Citaion:[Chinese Journal of Contemporary Pediatrics,2022,24(8):881-886]