Zhao Yajie, Zhang Xiucai, Torres Von Vergel L, Liu Haiyang, Rocker Andrea, Zhang Yizhi, Wang Jiawei, Chen Lijiang, Bi Wenzi, Lin Jie, Strugnell Richard A, Zhang Siqin, Lithgow Trevor, Zhou Tieli, Cao Jianming
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Public Health. 2019 Aug 19;7:229. doi: 10.3389/fpubh.2019.00229. eCollection 2019.
Carbapenem-resistant, hypervirulent (CR-hvKP) has recently emerged as a significant threat to public health. In this study, 29 isolates were isolated from eight patients admitted to the intensive care unit (ICU) of a comprehensive teaching hospital located in China from March 2017 to January 2018. Clinical information of patients was the basis for the further analyses of the isolates including antimicrobial susceptibility tests, identification of antibiotic resistance and virulence gene determinants, multilocus sequence typing (MLST), -macrorestriction by pulsed-field gel electrophoresis (PFGE). Selected isolates representing distinct resistance profiles and virulence phenotypes were screened for hypervirulence in a larvae infection model. In the course of the outbreak, the overall mortality rate of patients was 100% ( = 8) attributed to complications arising from CR-hvKP infections. All isolates except one (28/29, 96.6%) were resistant to multiple antimicrobial agents, and harbored diverse resistance determinants that included the globally prevalent carbapenemase . Most isolates had hypervirulent genotypes being positive for 19 virulence-associated genes, including (25/29, 86.2%), (27/29, 93.1%), (27/29, 93.1%), (29/29, 100%), (29/29, 100%), and (29/29, 100%). MLST revealed ST11 for the majority of isolates (26/29, 89,7%). Infection assays demonstrated high mortality in the model with the highest LD values for three isolates (<10 CFU/mL) demonstrating the degree of hypervirulence of these CR-hvKP isolates, and is discussed relative to previous outbreaks of CR-hvKP.
耐碳青霉烯类、高毒力（CR-hvKP）最近已成为对公共卫生的重大威胁。在本研究中，于2017年3月至2018年1月从中国一家综合性教学医院重症监护病房（ICU）收治的8例患者中分离出29株菌株。患者的临床信息是对分离株进行进一步分析的基础，包括抗菌药物敏感性试验、抗生素耐药性和毒力基因决定因素的鉴定、多位点序列分型（MLST）、脉冲场凝胶电泳（PFGE）进行的宏观限制性分析。在幼虫感染模型中筛选代表不同耐药谱和毒力表型的选定分离株的高毒力情况。在疫情爆发期间，患者的总体死亡率为100%（n = 8），原因是CR-hvKP感染引起的并发症。除1株外，所有分离株（28/29，96.6%）对多种抗菌药物耐药，并携带多种耐药决定因素，包括全球流行的碳青霉烯酶。大多数分离株具有高毒力基因型，19个毒力相关基因呈阳性，包括rmpA（25/29，86.2%）、rmpA2（27/29，93.1%）、entB（27/29，93.1%）、K1（29/29，100%）、K2（29/29，100%）和ureC（29/29，100%）。MLST显示大多数分离株为ST11型（26/29，89.7%）。感染试验表明，在幼虫模型中死亡率很高，三株分离株的最低致死剂量值（<10 CFU/mL）最高，证明了这些CR-hvKP分离株的高毒力程度，并与之前的CR-hvKP疫情爆发情况进行了讨论。
