Identification of Two Novel Carbapenemase-Encoding Hybrid Plasmids Harboring bla(NDM-5) and bla(KPC-2) in a Clinical ST11-KL47 Klebsiella pneumoniae

BACKGROUND: Emergence of bla(KPC) and bla(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(NDM−5) and bla(KPC−2). Both plasmids were shown to be novel hybrid plasmids and IS26 played an important role in generation of two plasmids. Gene bla(KPC-2) was flanked by the NTEKPC-Ib-like genetic structure (IS26-ΔTn3-ISKpn8-bla(KPC-2)-ISKpn6-IS26) and was located on a conjugative IncFII/R/N type hybrid plasmid. CONCLUSION: The resistance gene bla(NDM−5) located on a region organized as IS26-bla(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.