北京某医院耐碳青霉烯类抗生素肺炎克雷伯菌分子流行病学研究

Molecular epidemiology of carbapenem resistant KlebsieUa pneumoniae in a hospital in Beijing

目的 分析北京某医院分离的耐碳青霉烯类抗生素肺炎克雷伯菌（CRKP）的分子流行病学特征。方法 实验菌株来源于2010年5月至2015年10月在北京某三甲医院分离的所有对碳青霉烯类抗生素呈现耐药性的肺炎克雷伯菌。同一患者剔除相同部位的重复分离菌株后，一共375株被纳入本研究。采用PFGE对CRKP进行分型，并挑选不同PFGE型别的代表菌株开展多位点序列分型（MLST）、常见碳青霉烯类抗生素耐药基因（blaKPC、blaNDM、blaIMP、blaVIM、blaOXA-48）检测和全基因组测序分析；挑选1株CRKP（A1502）进行基于全基因组的分型，分析该菌株和其他医院和其他地区分离株之间的遗传进化关系。结果 375株CRKP分为140个PFGE型别，其中5个型别包含的菌株数大于5株，为优势型别，分别为KPX01.CN0058（128株）、KPX01.CN0014（36株）、KPX01.CN0268（16株）、KPX01.CN0265（12株）和KPX01.CN0438（7株）。不同的优势PFGE型别分布在不同的时间段和病区。MLST分型结果显示，15株代表菌株中有13株为ST11型KPC-2菌株。在全基因组分型聚类树中，A1502与分离自北京其他医院的菌株聚集成簇，而与分离自上海、杭州的菌株聚类关系较远。结论 该医院CRKP分离株存在优势基因型别，流行的克隆群为携带KPC-2基因的ST11型；该克隆群存在医院内和医院间的传播扩散。

Objective To reveal the molecular epidemiological characteristics of Carbapenem-Resistant Klebsiella pneumoniae （CRKP） isolated from a three level teaching hospital in Beijing.Methods Pulsed field gel electrophoresis （PFGE） was carried out to subtyping 375 CRKP isolated in that hospital between May 2010 and October 2015. Fifteen strains were chose based on the PFGE patterns to be analyzed by multi-locus sequence typing （MLST） and detection of carbapenem-resistance genes. One strain （A1502） was selected for whole genome sequencing and analyzing.Results The 375 CRKP were divided into 140 PFGE types, among which five types contained more than five strains. The dominant types were distributed in different time periods and wards. Among the 15 strains tested by MLST and carbapenem-resistance genes detection, 13 were ST11 strains carrying KPC-2 gene. By genome-based typing, A1502 was clustered together with strains from other hospitals of Beijing but far from the strains from Shanghai and Hangzhou.Conclusion The CRKP epidemic clone （ST11 clone carrying KPC-2） has been spreading within single hospital and across different hospitals in Beijing.