Global emergence of carbapenem-resistant Klebsiella pneumoniae co-carrying multiple carbapenemases

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) co-carrying multiple carbapenemases is complicating clinical treatment. This study aimed to investigate the global dissemination trends of CRKP strains that co-carry multiple carbapenemases. The CRKP isolate KP424 co-carrying bla(NDM-1) and bla(KPC-2), recovered from a stool specimen, was identified by the NG-Test Carba 5 test, and the genome sequence was further determined by using Nanopore MinION and Illumina NovaSeq 6000 technologies. The genome sequences of the CRKP strains carrying multiple carbapenemase genes were further retrieved from the NCBI GenBank database. Thirteen antimicrobial resistance genes, including bla(NDM-1) and bla(KPC-2), have been identified in KP424, with bla(NDM-1) and bla(KPC-2) located on different plasmids. In total, 832 genome sequences of CRKP strains co-carrying two carbapenemase genes were retrieved from the NCBI database. Strains carrying both bla(NDM) and bla(OXA-48-like) accounted for 665 (79.9 %) of the total strains, ranking first, and those carrying both bla(KPC) and bla(NDM) accounted for 103 (12.4 %), ranking second. The prevalence of CRKP strains co-carrying two carbapenemase genes increased significantly over time, from 0.40 % in 2010 to 9.67 % in 2021. The proportion of strains carrying both bla(KPC) and bla(NDM) has also increased, from 0.00 % in 2010 to 4.40 % in 2021. The strains carrying both bla(KPC) and bla(NDM) had the highest prevalence (66.7 %, 52/78) in China, while those carrying both bla(NDM) and bla(OXA-48-like) had the highest prevalence worldwide. Multiple-carbapenemase producers pose a great threat to public health; further research on the mechanisms underlying multiple carbapenemase gene occurrence is required to prevent their global dissemination.