Emergence of a Fatal ST11-KL64 Tigecycline-Resistant Hypervirulent Klebsiella pneumoniae Clone Cocarrying bla(NDM) and bla(KPC) in Plasmids

作者全名："Huang, Jinzhu; Yi, Miao; Yuan, Yaling; Xia, Peiwen; Yang, Bingxue; Liao, Jiajia; Dang, Zijun; Luo, Shengli; Xia, Yun"

作者地址："[Huang, Jinzhu; Yi, Miao; Yuan, Yaling; Xia, Peiwen; Yang, Bingxue; Liao, Jiajia; Dang, Zijun; Luo, Shengli; Xia, Yun] Chongqing Med Univ, Dept Lab Med, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Xia, Y (通讯作者)，Chongqing Med Univ, Dept Lab Med, Affiliated Hosp 1, Chongqing, Peoples R China."

来源：MICROBIOLOGY SPECTRUM

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000865779200001

JCR分区：Q2

影响因子：3.7

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：KPC and NDM; ST11-KL64; hvKP; tigecycline resistance

摘要："Infections with CRKP coproducing KPC and NDM currently have limited clinical antibacterial options, and tigecycline is used as the last line of defense for therapy. However, this study found that CR-hvKP infection with tigecycline resistance, which may lead to many bacteria being resistant to most commonly used antibiotics, brought significant challenges to clinical treatment. The clonal propagation of ST11-KL64 CRKP should receive sufficient attention. The combination of hypervirulent Klebsiella pneumoniae (hvKP) infection with carbapenem and tigecycline resistance leads to significant challenges to clinical treatment, with limited available antibiotics and poor patient prognoses. The hvKP12 isolate was obtained from a blood sample of a 74-year-old female in a Chinese teaching hospital. Whole-genome sequencing and microbial characterization were performed to understand the evolutionary mechanism of its resistance. The patient infected with hvKP12 died due to pyemia after a 17-day tigecycline treatment. The antimicrobial susceptibility test identified that hvKP12 was resistant to tigecycline and carbapenems. Variants of tet(A) and the overexpression of efflux pumps related to tigecycline resistance were detected in hvKP12. Conjugation experiments with bla(NDM) and bla(KPC) plasmids failed in the laboratory environment. Additionally, phylogenetic analysis suggested that hvKP12 was a clinical high-risk clone of ST11-KL64. We found that the bla(KPC-2) gene segment was formed by IS26-mediated gene cluster translocation. Interestingly, the evolutionary pathway of hvKP12 suggested that the KPC-2-producing carbapenem-resistant K. pneumoniae (KPC-2-CRKP) strain evolved into a KPC-NDM-CRKP strain by acquiring the NDM plasmid. To our knowledge, this is the first report of tigecycline-resistant ST11-KL64 carbapenem-resistant hvKP (CR-hvKP) bacteria coproducing bla(KPC) and bla(NDM), causing a fatal blood infection. IMPORTANCE Infections with CRKP coproducing KPC and NDM currently have limited clinical antibacterial options, and tigecycline is used as the last line of defense for therapy. However, this study found that CR-hvKP infection with tigecycline resistance, which may lead to many bacteria being resistant to most commonly used antibiotics, brought significant challenges to clinical treatment. The clonal propagation of ST11-KL64 CRKP should receive sufficient attention."

基金机构：National Natural Science Foundation of China [X1919XYTSC]

基金资助正文：This study was supported by the National Natural Science Foundation of China (X1919XYTSC).