血流感染肺炎克雷伯菌临床特征、毒力基因及分子流行病学研究

摘要：目的 探讨血流感染肺炎克雷伯菌(KPN)的临床及分子生物学特征。方法 收集2019年1月-2020年12月，血流感染患者血液分离的KPN。应用Microflex LT型质谱仪进行菌种鉴定，Vitek-2分析仪进行药敏试验，结果判定参照CLSI 2019版标准。检测KPN多位点序列分型、荚膜分型及毒力因子等。应用全基因组测序技术分析其中碳青霉烯类耐药KPN(CRKP)分子生物学特征。结果 2年内共有72株KPN纳入研究，根据感染类型分为医院感染(HABSI)组(39株，54.2%)及社区感染(COBSI)组(33株，45.8%)。在入住ICU＞10d、侵袭性诊疗、使用碳青霉烯类药物和死亡或放弃治疗方面，HABSI组患者的比例高于COBSI组(P<0.05)。HABSI组对常用抗菌药物的耐药率高于COBSI组。HABSI组菌株中共检出19株CRKP(26.4%)，94.7%的CRKP携带blaKPC-2，主要为K64-ST11型，且存在高度亲缘关系，所有K64-ST11型CRKP均携带IncHI1B型质粒。结论 血流感染患者血液分离的CRKP呈现多重耐药，K64-ST11型为其主要分子型别，携带多种质粒介导的毒力因子，且存在医院内感染的克隆播撒。

Clinical characteristics,virulence genes,and molecular epidemiology of Klebsiella pneumoniae in bloodstream infection

Abstract Objective To investigate the clinical characteristics and molecular biological characteristics of Klebsiella pneumoniae (KPN) in bloodstream infection. Methods KPN of patients with bloodstream infection were collected from January 2019 to December 2020. Bruker MicroFlex LT was used for isolate identification; Vitek-2 analyzer was used for antimicrobial susceptibility testing. The results of antimicrobial sensitivity were determined according to CLSI 2019 standard. The multilocus sequence typing and virulence factors of KPN were detected. Carbapenem-resistant K. pneumoniae (CRKP) were sequenced by whole genome sequencing, and their related molecular biological characteristics were analyzed. Results A total of 72 KPN isolates were included in the study in two years. They were divided into hospital-acquired infection (HABSI) group (39 isolates, 54.2%) and community-onset infection (COBSI) group (33 isolates, 45.8%) according to the type of infection. The proportion of patients in HABSI group was higher than that in COBSI group in terms of ICU > 10 days, invasive operation, use of carbapenems, and death or giving up treatment . The resistance rate of HABSI group was higher than that of COBSI group. A total of 19 CRKP (26.4%) were detected in HABSI group. 94.7% CRKP carried blaKPC-2, which mainlybelonged to the K64-ST11 type, and there was a high degree of genetic relationship. All K64-ST11 CRKP carried IncHI1B plasmid. Conclusion CRKP isolated from bloodstream infection patients showed multiple drug resistance, and K64-ST11 was the main molecular type. K64-ST11 CRKP carried a variety of plasmid mediated virulence factors and existed clonal