Genomic surveillance of carbapenem-resistant Klebsiella pneumoniae reveals a prolonged outbreak of extensively drug-resistant ST147 NDM-1 during the COVID-19 pandemic in the Apulia region (Southern Italy)

The recent worldwide spread of New Delhi Metallo-beta-lactamase-producing Klebsiella pneumoniae (NDM-KP) in healthcare settings remains a concern. The aim of the study was to describe an outbreak of extensively drug-resistant (XDR) ST147 NDM-1-KP in the Apulia region of Southern Italy that occurred between 2020 and 2022 through genomic surveillance of carbapenem-resistant Enterobacterales. Overall, 459 carbapenem-resistant KP (CR-KP) isolates collected from patients hospitalized with bloodstream infections were tested using a commercial multiplex real-time PCR to identify carbapenemase genes. A subset of 27 isolates was subjected to whole-genome sequencing (WGS). Core-genome Multilocus Sequence Typing (cg-MLST) was performed by analyzing a panel of 4,884 genes. Molecular testing revealed that 104 (22.6%) isolates carried the carbapenemase NDM gene. Phylogenetic analysis of the 27 isolates subjected to WGS revealed high genetic relatedness among strains. All isolates were resistant to all first-line antibiotics. Virulome analysis identified the ybt locus, the two well-recognized virulence factors iucABCDiutA and rmpA, and the genes encoding the Type 3 pilus virulence factor. Plasmids IncFIB(pkPHS1), IncFIB(pNDM-Mar), IncFIB(pQil), IncHI1B(pNDM-MAR), IncR and Col(pHAD28) were identified in all isolates. Moreover, further analysis identified the IncFIB-type plasmid carrying the NDM-1 genes. The increasing circulation of XDR NDM-1 ST147 KP strains in Southern Italy in recent years is worrisome because these clones pose a real risk, particularly in hospital settings. Genomic surveillance is a crucial tool for early identification of emerging threats such as the spread of high-risk pathogens. Rapid infection control measures and antimicrobial stewardship are key to preventing further spread of hypervirulent KP strains.