OBJECTIVES: Across recent decades the increasing prevalence of multi-drug resistant KPC-carrying K. pneumoniae (KPC-Kp) has become a worldwide public concern. Herein, we characterized a ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (MER-VAB) and imipenem/relebactam (IMI-REL) resistant KPC-Kp strain isolated from a critically ill transplanted patient. METHODS: Antimicrobial susceptibility test and whole-genome sequencing (WGS) were conducted to characterize the strain at the phenotypic and the genotypic levels. Genomic DNA was sequenced using the Illumina platform. Bioinformatic analyses were used to investigate the genome sequences both for resistance and virulence features, and for characterization of plasmids. RESULTS: The phenotypic characterization revealed that the KPC-Kp isolate was highly resistant to a wide range of antibiotics, including all the beta-lactam/beta lactamase inhibitor combinations, such as CAZ/AVI, MER-VAB, IMI-REL, and cefiderocol (FDC). WGS analysis showed that the isolate, belonging to the rare lineage ST661, contained several resistance and virulence genes. Among the resistance genes, we identified a new KPC variant, inside the mobile genetic element Tn4401, KPC-245, characterized by an insertion of 9 aminoacids (RAPNKDDYT) at position 263 and an aminoacidic change E274D of the protein sequence, compared to KPC-3. Interestingly, the presence of mutations only in bla CONCLUSIONS: In our study, by using WGS analysis on a clinical isolate, we identified a new bla