BACKGROUND Emergence of KPC-2 and NDM-1-coproducing carbapenem-resistant Klebsiella pneumoniae (KPC-2-NDM-1-CRKP) has escalated threat of CRKP to healthcare. Currently, only 4 isolates had been reported sporadically. It remains unclear how KPC-2-NDM-1-CRKPs emerged, and whether they are stable and have transmission capacity. METHODS PCR and Sanger sequencing was used to screen carbapenemase genes for 2057 CRKP isolates, to identify KPC-2-NDM-1-CRKPs. The clinical information of the patients was collected from medical records. Antimicrobial susceptibility, plasmid stability, plasmid conjugation and growth curve were measured. The whole genomes were sequenced on PacBio and Illumina platforms. Similar plasmids were searched against public database. Phylogenetic tree was built based on related genomes which carried similar plasmids, to infer the evolutionary history of KPC-2-NDM-1-CRKP. FINDINGS We identified to date the largest cohort of 7 KPC-2-NDM-1-CRKPs. An increased incidence rate was observed. Plasmid transferability assay and phylogenic analysis suggested an evolutionary pathway that KPC-2-NDM-1-CRKP emerged from a KPC-2-CRKP progenitor which acquired another highly transferable blaNDM-1 plasmid later. Further, demographics and stability test revealed that these isolates were stable and had the potential for transmission among patients. INTERPRETATION Our study extends our concern on KPC-2-NDM-1-CRKP about its high stability and non-inferior fitness, sheds light on the evolution of KPC-2-NDM-1-CRKP, strengthens the importance of continued surveillance on these isolates, and would improve clinical treatment and management. FUNDING This work was supported by National Natural Science Foundation for Distinguished Young Scholars of China (81625014) and NSFC-RCUK-MRC (81661138006).

中文翻译：

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临床环境中 NDM-1 和 KPC-2 共同产生的肺炎克雷伯菌的可转移性和进化。


背景KPC-2和NDM-1共产的碳青霉烯类耐药肺炎克雷伯菌（KPC-2-NDM-1-CRKP）的出现加剧了CRKP对医疗保健的威胁。目前，仅零星报告了4株分离株。目前尚不清楚KPC-2-NDM-1-CRKP是如何出现的，以及它们是否稳定并具有传输能力。方法采用PCR和Sanger测序技术筛选2057株CRKP菌株的碳青霉烯酶基因，鉴定KPC-2-NDM-1-CRKP。患者的临床信息是从医疗记录中收集的。测量抗菌敏感性、质粒稳定性、质粒缀合和生长曲线。整个基因组在 PacBio 和 Illumina 平台上进行了测序。在公共数据库中搜索了类似的质粒。根据携带相似质粒的相关基因组构建系统发育树，以推断KPC-2-NDM-1-CRKP的进化历史。结果 我们确定了迄今为止最大的 7 个 KPC-2-NDM-1-CRKP 队列。观察到发病率增加。质粒可转移性测定和系统发育分析表明KPC-2-NDM-1-CRKP从KPC-2-CRKP祖细胞中出现的进化途径，该祖细胞后来获得了另一个高度可转移的blaNDM-1质粒。此外，人口统计和稳定性测试表明，这些分离株是稳定的，并且有可能在患者之间传播。解释我们的研究扩展了我们对 KPC-2-NDM-1-CRKP 的高稳定性和非劣适应性的关注，揭示了 KPC-2-NDM-1-CRKP 的进化，加强了持续监测这些的重要性分离，并将改善临床治疗和管理。 资助这项工作得到了国家自然科学基金杰出青年基金 (81625014) 和 NSFC-RCUK-MRC (81661138006) 的支持。