Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring in China with an IncR plasmid.

The rise of carbapenem-resistant coharboring KPC-2 and NDM-1 poses a significant public health threat. KPC-2-NDM-1- is rarely reported in clinical settings. In this study, we report the largest cohort of eight KPC-2-NDM-1- isolated from children with urinary tract infections. Comprehensive characterization, including antimicrobial susceptibility testing, plasmid conjugation, whole-genome sequencing, and comparative genomics, was conducted for these clinical strains. Antimicrobial susceptibility testing indicated that all strains were resistant to meropenem [minimal inhibitory concentration (MICs) ≥ 8 µg/mL] and imipenem (MICs > 8 µg/mL). Genotyping and comparative genomics analyses identified the eight KPC-2-NDM-1- belonging to ST523, exhibiting a close relationship characterized by 45 single nucleotide polymorphisms. Whole-genome sequencing and plasmid analysis confirmed the presence of and on an IncR plasmid named pC275-2 with 46,050 bp. The was integrated within the related region, which includes ΔIS, , , , , and IS, while the gene was located on a novel non-Tn genetic element. The genetic architectures containing differed from classical structures, underscoring the ongoing evolution of these genetic elements.IMPORTANCEOur study described the largest cohort to date of eight ST523 KPC-2-NDM-1- isolated from children with urinary tract infections. The cooccurrence of KPC-2, a serine -lactamases, and NDM-1, a metallo-β-lactamase on an IncR plasmid pC275-2 from a clinical carbapenem-resistant . . The conserved insertion structure mediated the , and the propagation of gene with a new genetic background using IncR plasmid in clinical settings promotes the emergence of superbugs necessitating vigilant monitoring. Our research detected that ST523 KPC-2- NDM-1- were disseminated in a children's hospital. The potential spread of an IncR plasmid within the hospital raises concerns about the pandemic potential of this clone that produces two carbapenemases: KPC-2 and NDM-1. Further investigations will be necessary to control and prevent the spread of KPC-2-NDM-1-s.