Identification of Two Novel Carbapenemase-Encoding Hybrid Plasmids Harboring [bla.sub.NDM-5] and [bla.sub.KPC-2] in a Clinical ST11-KL47 Klebsiella pneumoniae

Background: Emergence of [bla.sub.KPC] and [bla.sub.NDM] co-harboring Klebsiella pneumoniae has escalated the threat of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to healthcare. It remains unknown the prevalence and molecular characteristics of CRKP co- producing KPC and NDMs carbapenemases in Henan. Methods and Results: Twenty-seven CRKP strains isolated from different times were selected randomly in affiliated cancer hospital of Zhengzhou University from January 2019 to January 2021, among which one KPC-2 and NDM-5 positive CRKP named K9 was isolated from an abdominal pus sample of a 63-year-old male patient with leukemia. Sequencing of K9 determined that K9 belonged to ST11-KL47, which is resistant to antibiotics such as meropenem, ceftazidime- avibactam and tetracycline. K9 carried two different plasmids that contained [bla.sub.NDM-5] and [bla.sub.KPC-2]. Both plasmids were shown to be novel hybrid plasmids and IS26 played an important role in generation of two plasmids. Gene [bla.sub.KPC-2] was flanked by the [NTE.sub.KPC]-Ib-like genetic structure (IS26-ATn3-ISKpn8-[bla.sub.KPC-2]-ISKpn6-IS26) and was located on a conjugative IncFII/R/N type hybrid plasmid. Conclusion: The resistance gene [bla.sub.NDM-5] located on a region organized as IS26-[bla.sub.NDM-5]-ble-trpF-dsbD- ISCR1-sul1-aadA2-dfrA12-IntI1-IS26 was carried by a phage-plasmid. We described a clinical CRKP co-producing KPC-2 and NDM-5 and emphasized an urgent need to control their further spread. Keywords: carbapenem-resistant Klebsiella pneumoniae, KPC-2, NDM-5, beta- lactamases, hybrid plasmid, IS26