Emergence and Dissemination of NDM+OXA-48-like Co-Producing Klebsiella pneumoniae in a Regional Healthcare Network: Seven-Year Surveillance from Latium, Italy

Background/Objectives: The epidemiology of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) in Europe is evolving towards an increasing contribution of metallo-β-lactamases (MBLs). In particular, co-production of New Delhi metallo-β-lactamase (NDM) and OXA-48-like carbapenemases represents a major concern due to limited therapeutic options and epidemic potential. We aimed to describe temporal trends and genomic characteristics of NDM and OXA-48-like co-producing K. pneumoniae within a regional surveillance programme targeting ceftazidime-avibactam (CZA)-resistant carbapenem-resistant Enterobacterales (CRE) in the Latium Region, Italy. Methods: Between January 2019 and December 2025, CZA-resistant CRE isolates were collected through a regional surveillance network. Antimicrobial susceptibility testing and carbapenemase detection were performed, and NDM-producing K. pneumoniae (NDM-Kpn) was analysed by whole-genome sequencing (WGS). Genomic analyses included multi-locus sequence typing, assessment of clonal relatedness, and resistome/virulome profiling. Results: A total of 2752 non-repetitive CZA-resistant CRE were collected. The analysis of CZA-resistant K. pneumoniae isolates submitted to the regional surveillance network showed that the proportion of NDM producers increased markedly from 2023 onwards. In particular, NDM in association with OXA-48-like reached 26.0% in 2024 and 43.6% in 2025, becoming the predominant carbapenemase profile within this selected surveillance population. WGS of 437 NDM-Kpn revealed a structured population dominated by Sequence Type (ST)147 (63.2%), widely disseminated across 24 hospitals and characterised by a predominant NDM-1 variant and OXA-48-like co-producing profile associated with KL10/wzi420 capsular type. A subset of isolates, mainly within the ST147-KL64 subgroup, showed higher virulence scores, indicating a possible convergence of resistance and virulence. Conclusions: Our findings indicate a rapid shift towards NDM-mediated resistance among CZA-resistant K. pneumoniae submitted to the regional surveillance network, with the emergence of NDM and OXA-48-like co-producing isolates associated with a dominant ST147 clone detected across multiple hospitals. These results highlight the urgent need for coordinated genomic surveillance and infection prevention strategies.