Raw data-Molecular epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae Risk factors and resistance mechanism of ceftazidimeavibactam in China.xlsx

The high morbidity and mortality rates associated with carbapenem-resistant hypervirulent <i>Klebsiella pneumoniae</i>(CR-hvKP) have become a global public health problem. This study explored the optimal concentration of a novel β-lactam/inhibitor and the resistance mechanism of ceftazidime/avibactam of CR-hvKP. We analyzed the whole genome sequence and epidemiological data of 81 carbapenem-resistant <i>Klebsiella pneumoniae</i>(<i>KP</i>) strains and conducted sensitivity experiments to explore the optimal concentration of carbapenem-resistant <i>Klebsiella pneumoniae</i>(CRKP).We verified the resistance and virulence genes of CRKP<i> </i>using polymerase chain reaction and compared virulence between CRKP and carbapenem-resistant-non-hypervirulent <i>Klebsiella pneumoniae</i>(CR-non-hvKP) through <i>Galleria mellonella</i> assays. The prevalent types of multilocus sequence typing in our CRKP<i> </i>strains were ST11 (69.14%, 56/81). ST11-K64-O1/O2v1 has become an epidemic type in our hospital, with drug-resistance genes dominated by bla_KPC-2 (90.12%, 73/81). Ceftazidime/avibactam has better antibacterial effects on CRKP, and its resistance is mainly mediated by a resistance plasmid containing the bla_KPC-2 gene. 52 CR-hvKP strains carry the bla_KPC-2, with a high detection rate of siderophore. Further research has shown that the genetic environment of the bla_KPC-2 contains TnpR_Tn3 and ISKpn27 upstream and ISKpn6 insertion sequences downstream. <i>Galleria mellonella</i> revealed that the survival rate of CR-hvKP was lower than that of CR-non-hvKP. Antibiotic usage time, Carbapenem antibiotic exposure, and Malignant tumors were independent risk factors for CR-hvKP infection. The spread of CR-hvKP strains is alarming, necessitating molecular monitoring of hypervirulent strains and strengthening the nosocomial infection prevention and control measures. Antibiotics should be used reasonably based on patients' infection status and local epidemiological data.

碳青霉烯耐药高毒力<i>肺炎克雷伯菌</i>（CR-hvKP）的高发病率和死亡率已成为全球公共卫生问题。本研究旨在探索新型β-内酰胺/抑制剂的最佳浓度，以及CR-hvKP对头孢他啶/阿维巴坦的耐药机制。我们分析了81株碳青霉烯耐药<i>肺炎克雷伯菌</i>（<i>KP</i>）的全基因组序列与流行病学数据，并通过敏感性实验探究碳青霉烯耐药<i>肺炎克雷伯菌</i>（CRKP）的最佳浓度。我们采用聚合酶链反应（PCR）验证CRKP的耐药基因与毒力基因，并通过<i>大蜡螟</i>（<i>Galleria mellonella</i>）测定比较CRKP与碳青霉烯耐药非高毒力<i>肺炎克雷伯菌</i>（CR-non-hvKP）的毒力差异。我们的CRKP菌株中流行的多位点序列分型类型为ST11（69.14%，56/81）。ST11-K64-O1/O2v1已成为我院的流行菌株类型，耐药基因以bla_KPC-2为主（90.12%，73/81）。头孢他啶/阿维巴坦对CRKP具有较好的抗菌效果，其耐药性主要由携带bla_KPC-2基因的耐药质粒介导。52株CR-hvKP携带bla_KPC-2基因，且铁载体检出率较高。进一步研究显示，bla_KPC-2的遗传环境上游包含TnpR_Tn3和ISKpn27序列，下游则存在ISKpn6插入序列。<i>大蜡螟</i>测定结果表明，CR-hvKP感染组的存活率低于CR-non-hvKP感染组。抗生素使用时长、碳青霉烯类抗生素暴露史及恶性肿瘤是CR-hvKP感染的独立危险因素。CR-hvKP菌株的传播态势令人担忧，亟需对高毒力菌株开展分子监测，并强化医院感染防控措施。临床应根据患者感染状况及当地流行病学数据合理使用抗生素。