National genomic surveillance reveals global plasmid and chromosomal dissemination routes of blaNDM-1

The global spread of New Delhi metallo-β-lactamase (NDM)–producing Gram-negative bacteria poses a major threat to healthcare systems worldwide, yet the processes driving their long-term establishment at national scales remain poorly understood. Here, we integrate a decade of nationwide surveillance with high-resolution genomics to reconstruct the emergence, dissemination, and evolution of bla NDM in Costa Rica, from its first detection in 2014 to a major hospital outbreak during the COVID-19 pandemic. National surveillance confirmed hundreds of bla NDM -positive isolates, revealed widespread dissemination across hospitals, and identified a temporal shift in dominant bla NDM hosts from 2020 onwards. During the pandemic, increased NDM detection coincided with a large intrahospital outbreak involving 247 patients with a 51% case-fatality rate. Genomic analysis of 40 representative isolates revealed both plasmid- and chromosome-associated bla NDM-1 -carriage and heterogeneous dissemination through globally disseminated high-risk and locally emerging clones. Plasmid-resolved analyses showed that the dominant IncA/C2 bla NDM-1 -carrying plasmid derived from a globally conserved backbone and diversified into multiple circulating variants and fusion events with IncF elements, generating multidrug-resistant megaplasmids. Together, these findings highlight how global connectivity, local population dynamics, and plasmid plasticity interact to drive the national persistence of bla NDM and underscore the importance of sustained genomic surveillance.