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New resistance threat in difficult-to-treat resistance Pseudomonas aeruginosa co-producing AFM and KPC carbapenemases: plasmid dynamic transfer and global phylogeography perspective
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DOI：10.1080/22221751.2025.2585632.png)
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Abstract
En 中文
Metallo-β-lactamase (MBL) production is one of the primary carbapenem resistance mechanisms in carbapenem-resistantPseudomonas aeruginosa(CRPA). The emergence of the novel MBL geneblaAFMposes a significant threat to global public health. Concerningly, we have identified clinical CRPA strains co-producing AFM and the widely-disseminated carbapenemase KPC-2. Here, we describe AFM-producing, KPC-2-producing, and AFM/KPC-2 co-producing clinical CRPA isolates that were collected from three patients in two different hospital buildings in China. Comparative genomics suggested horizontal transfer of ablaAFM-2-harboring plasmid may have contributed to the spread of the AFM carbapenemase between different hospital areas, and to the emergence of dual carbapenemase-producing CRPA. Further epidemiological source tracing revealed the likely involvement of cross-patient nursing care and cross-area patient transfer in carbapenemase transmission. Experimental data confirmed the transfer ability of clinicalblaAFM-2-bearing plasmids intoP. aeruginosaPAO1. As the global epidemiology ofblaAFMhas not been systematically evaluated, we further examined 30,800 publicly availableP. aeruginosagenome sequences. Including those generated in this study,blaAFMgenes were detected in 36 isolates in total, which were derived from China (35/36) or Australia (1/36). AFM-containing genomes were sourced from six Chinese provinces, with 63.9% (23/36) isolated in Zhejiang between 2020 and 2024. The most prominent AFM-associatedP. aeruginosaclone was ST463 (17/36 genomes). Our study highlights the concerning challenge presented byblaAFM-harboring CRPA in clinical settings. Horizontal transfer ofblaAFM-bearing plasmids can contribute to difficult-to-treat resistance (DTR) phenotypes. Surveillance should be strengthened to prevent the further spread of these plasmids, particularly into and within ICUs.
Keywords:
Carbapenem-resistant P. aeruginosa
AFM and KPC
plasmid transfer
ICU
global surveillance
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