Genomic and Phenotypic Insights into Carbapenemase-Mediated Resistance and Clonal Diversity of Pseudomonas aeruginosa Clinical Isolates from Southern Brazil

Abstract Pseudomonas aeruginosa is a major opportunistic pathogen associated with high morbidity in hospitalized patients due to its intrinsic and acquired resistance mechanisms. Carbapenem resistance, often mediated by the production of carbapenemase, poses a critical therapeutic challenge worldwide. This study investigated the genomic organization, molecular diversity, and plasmid-mediated dissemination of carbapenemase genes in P. aeruginosa isolates from hospitals in Paraná and Santa Catarina, Brazil, and explored their correlation with phenotypic resistance profiles. Eight isolates (80%) were classified as extensively drug-resistant (XDR), showing broad resistance to β-lactams, carbapenems, and β-lactam/β-lactamase inhibitor combinations. Multi-Locus Sequence Typing revealed a heterogeneous clonal structure, with ST1560 being the predominant type (30%). Multiple β-lactamase genes were identified, including chromosomal bla PDC variants, bla OXA-50, and carbapenemase genes bla SPM-1, bla IMP-16, bla IMP-1, bla VIM-2, bla KPC-2, and bla NDM-1. Notably, 40% of isolates carried plasmid-borne carbapenemase genes, indicating a potential for horizontal gene transfer. Isolate 20,783 exhibited high resistance despite lacking additional carbapenemase genes, suggesting alternative mechanisms such as efflux or porin loss. The predominance of XDR P. aeruginosa ,which harbors diverse carbapenemases, including plasmid-mediated determinants, underscores the complexity of antimicrobial resistance in Brazilian hospitals. The coexistence of multiple resistance mechanisms, coupled with clonal heterogeneity, highlights the urgent need for integrated genomic surveillance and targeted infection control strategies to mitigate the spread of multidrug-resistant P. aeruginosa in clinical settings.