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Abstract：
BACKGROUND: The occurrence of multidrug-resistant and hypervirulent Klebsiella pneumoniae (MDR-hvKp) worldwide poses a great challenge for public health. Few studies have focused on ST218 MDR-hvKp.
METHODS: Retrospective genomic surveillance was conducted at the Peking University Third Hospital from 2017 and clinical information was obtained. To understand genomic and microbiological characteristics, antimicrobial susceptibility testing, plasmid conjugation and stability, biofilm formation, serum killing, growth curves and whole-genome sequencing were performed. We also assessed the clinical and microbiological characteristics of ST218 compared with ST23.
RESULTS: A total of eleven ST218 Kp isolates were included. The most common infection type was lower respiratory tract infection (72.7%, 8/11) in our hospital, whereas ST23 hvKp (72.7%, 8/11) was closely associated with bloodstream infection. Notably, nosocomial infections caused by ST218 (54.5%, 6/11) was slightly higher than ST23 (36.4%, 4/11). All of the ST218 and ST23 strains presented with the virulence genes combination of iucA + iroB + peg344 + rmpA + rmpA2. Interestingly, the virulence score of ST218 was lower than ST23, whereas one ST218 strain (pPEKP3107) exhibited resistance to carbapenems, cephalosporins, β-lactamase/inhibitors and quinolones and harbored an ~ 59-kb IncN type MDR plasmid carrying resistance genes including blaNDM-1, dfrA14 and qnrS1. Importantly, blaNDM-1 and qnrS1 were flanked with IS26 located within the plasmid that could successfully transfer into E. coli J53. Additionally, PEKP2044 harbored an ~ 41-kb resistance plasmid located within tetA indicating resistance to doxycycline.
CONCLUSIONS: The emergence of blaNDM-1 revealed that there is great potential for ST218 Kp to become a high-risk clone for MDR-hvKp, indicating the urgent need for enhanced genomic surveillance.
METHODS: Retrospective genomic surveillance was conducted at the Peking University Third Hospital from 2017 and clinical information was obtained. To understand genomic and microbiological characteristics, antimicrobial susceptibility testing, plasmid conjugation and stability, biofilm formation, serum killing, growth curves and whole-genome sequencing were performed. We also assessed the clinical and microbiological characteristics of ST218 compared with ST23.
RESULTS: A total of eleven ST218 Kp isolates were included. The most common infection type was lower respiratory tract infection (72.7%, 8/11) in our hospital, whereas ST23 hvKp (72.7%, 8/11) was closely associated with bloodstream infection. Notably, nosocomial infections caused by ST218 (54.5%, 6/11) was slightly higher than ST23 (36.4%, 4/11). All of the ST218 and ST23 strains presented with the virulence genes combination of iucA + iroB + peg344 + rmpA + rmpA2. Interestingly, the virulence score of ST218 was lower than ST23, whereas one ST218 strain (pPEKP3107) exhibited resistance to carbapenems, cephalosporins, β-lactamase/inhibitors and quinolones and harbored an ~ 59-kb IncN type MDR plasmid carrying resistance genes including blaNDM-1, dfrA14 and qnrS1. Importantly, blaNDM-1 and qnrS1 were flanked with IS26 located within the plasmid that could successfully transfer into E. coli J53. Additionally, PEKP2044 harbored an ~ 41-kb resistance plasmid located within tetA indicating resistance to doxycycline.
CONCLUSIONS: The emergence of blaNDM-1 revealed that there is great potential for ST218 Kp to become a high-risk clone for MDR-hvKp, indicating the urgent need for enhanced genomic surveillance.
摘要：
背景：全球范围内多重耐药和高毒力肺炎克雷伯菌（MDR-hvKp）的发生对公共卫生构成了巨大挑战。很少有研究集中在ST218MDR-hvKp上。
方法：2017年在北京大学第三医院进行回顾性基因组监测，获得临床资料。了解基因组和微生物学特征，抗菌药物敏感性试验,质粒接合和稳定性，生物膜的形成，血清杀灭,进行生长曲线和全基因组测序.我们还评估了ST218与ST23的临床和微生物学特征。
结果：共包括11个ST218Kp分离株。最常见的感染类型是下呼吸道感染（72.7%，8/11）在我们医院，而ST23hvKp(72.7%，8/11）与血流感染密切相关。值得注意的是,ST218引起的医院感染(54.5%，6/11）略高于ST23（36.4%，4/11).所有ST218和ST23菌株均具有iucA+iroB+peg344+rmpA+rmpA2的毒力基因组合。有趣的是,ST218的毒力评分低于ST23，而一个ST218菌株（pPEKP3107）表现出对碳青霉烯类的抗性，头孢菌素,β-内酰胺酶/抑制剂和喹诺酮类药物，并带有携带抗性基因的〜59-kbIncN型MDR质粒，包括blaNDM-1，dfrA14和qnrS1。重要的是,blaNDM-1和qnrS1侧翼有位于质粒内的IS26,其可以成功转移到大肠杆菌J53中。此外,PEKP2044具有位于tetA内的〜41kb抗性质粒，表明对多西环素具有抗性。
结论：blaNDM-1的出现表明，ST218Kp有很大的潜力成为MDR-hvKp的高风险克隆，表明迫切需要加强基因组监测。
方法：2017年在北京大学第三医院进行回顾性基因组监测，获得临床资料。了解基因组和微生物学特征，抗菌药物敏感性试验,质粒接合和稳定性，生物膜的形成，血清杀灭,进行生长曲线和全基因组测序.我们还评估了ST218与ST23的临床和微生物学特征。
结果：共包括11个ST218Kp分离株。最常见的感染类型是下呼吸道感染（72.7%，8/11）在我们医院，而ST23hvKp(72.7%，8/11）与血流感染密切相关。值得注意的是,ST218引起的医院感染(54.5%，6/11）略高于ST23（36.4%，4/11).所有ST218和ST23菌株均具有iucA+iroB+peg344+rmpA+rmpA2的毒力基因组合。有趣的是,ST218的毒力评分低于ST23，而一个ST218菌株（pPEKP3107）表现出对碳青霉烯类的抗性，头孢菌素,β-内酰胺酶/抑制剂和喹诺酮类药物，并带有携带抗性基因的〜59-kbIncN型MDR质粒，包括blaNDM-1，dfrA14和qnrS1。重要的是,blaNDM-1和qnrS1侧翼有位于质粒内的IS26,其可以成功转移到大肠杆菌J53中。此外,PEKP2044具有位于tetA内的〜41kb抗性质粒，表明对多西环素具有抗性。
结论：blaNDM-1的出现表明，ST218Kp有很大的潜力成为MDR-hvKp的高风险克隆，表明迫切需要加强基因组监测。
