摘要
目的 了解全国临床分离碳青霉烯类耐药肠杆菌目细菌(carbapenem-resistant Enterobacterales,CRE)(除外肺炎克雷伯菌)对抗菌药物的敏感性、耐药机制和分子特征.方法 收集全国31个省、直辖市和自治区151所医疗机构2021年1-6月临床分离的CRE(除外肺炎克雷伯菌),按区域分别运送至三个中心实验室.中心实验室按照统一的实验方案进行菌种复核鉴定,肉汤微量稀释法测定CRE对抗菌药物的敏感性,所有菌株进行全基因组测序分析菌株产生的碳青霉烯酶基因和多位点序列分型(multilocus sequence typing,MLST).结果 共收集CRE菌株946株,其中大肠埃希菌、阴沟肠杆菌和其他肠杆菌目细菌分别占41.1％(389/946)、34.4％(325/946)和24.5％(232/946).药敏试验结果显示,大肠埃希菌、阴沟肠杆菌及其他肠杆菌目细菌对氨曲南-阿维巴坦、阿米卡星、黏菌素、多黏菌素B和替加环素均高度敏感,敏感率范围为87.1％～95.5％.全基因组测序显示blaNDM-5(71.7％,279/389)和blaNDM-1(64.3％,209/325)分别是大肠埃希菌和阴沟肠杆菌中主要流行的碳青霉烯酶基因类型.弗劳地枸橼酸杆菌和产气克雷伯菌中均以blaNDM-1为主,分别占73.8％(31/42)和57.8％(37/64);产酸克雷伯菌中,blaKPC-2和blaNDM-1分别占30.4％(14/46)和26.1％(12/46).MLST分型及地域分布显示大肠埃希菌共存在87种分型,主要以ST410(22.1％,86/389)和ST167(10.5％,41/389)型为主,前者主要分布在福建、河北、湖南、内蒙古、云南等地,后者主要分布在北京、海南、河南、辽宁、青海等地;阴沟肠杆菌共存在54种分型,主要以ST171(17.8％,58/325)和ST78(7.1％,23/325)型菌株为主,前者分布在安徽、河北、黑龙江、河南等地,后者多见于湖北、广西、贵州等地区.结论 产碳青霉烯酶是中国临床分离肠杆菌目细菌对碳青霉烯类药物耐药最主要的机制.中国不同省市分离的菌株克隆型存在较大差异.
Abstract
Objective To investigate the antimicrobial susceptibility,resistance mechanisms,and molecular characteristics of clinical isolates of carbapenem-resistant Enterobacterales(CRE)(except Klebsiella pneumoniae)in China.Methods The CRE strains(except K.pneumoniae)were isolated from 151 medical institutions in 31 provinces,municipalities and autonomous regions of China from January to June 2021 and tested in 3 central laboratories.The antimicrobial susceptibility of CRE was determined by broth microdilution method.Whole genome sequencing was performed to analyze the carbapenemase genes and multilocus sequence typing(MLST)of all strains.Results A total of 946 CRE strains were collected,among which Escherichia coli,Enterobacter cloacae and other Enterobacterales accounted for 41.1％(389/946),34.4％(325/946)and 24.5％(232/946),respectively.Antimicrobial susceptibility testing showed that E.coli,E.cloacae and other Enterobacterales were highly sensitive to aztreonam-avibactam,amikacin,colistin,polymyxin B and tigecycline,and 87.1％-95.5％of the strains were susceptible to these drugs.Whole genome sequencing indicated that blaNDM-5(71.7％,279/389)and blaNDM-1(64.3％,209/325)were the predominant carbapenemase gene types in E.coli and E.cloacae,respectively,while blaNDM-1 was predominant in C.freundii and K.aerogenes strains,accounting for 73.8％(31/42)and 57.8％(37/64),respectively.Among K.oxytogenes,blaKPC-2 and blaNDM-1 accounted for 30.4％(14/46)and 26.1％(12/46),respectively.A total of 87 ST types of E.coli were identified,mainly ST410(22.1％,86/389)and ST167(10.5％,41/389).ST410 E.coli was mainly isolated in Fujian,Hebei,Hunan,Inner Mongolia and Yunnan provinces,and ST167 E.coli was mainly isolated in Beijing,Hainan,Henan,Liaoning and Qinghai provinces.There were 54 ST types of E.cloacae,mainly ST171(17.8％,58/325)and ST78(7.1％,23/325).ST171 E.cloacae was mainly found in Anhui,Hebei,Heilongjiang and Henan provinces,while ST78 E.cloacae was mainly found in Hubei,Guangxi and Guizhou provinces.Conclusions Carbapenemase production is the main mechanism underlying carbapenem resistance of Enterobacterales in China.The clonotypes of CRE strains varied with geographic regions of China.
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