Abstract

--- - "BACKGROUND: Pseudomonas aeruginosa is a major cause of healthcare-associated infections and a World Health Organization priority pathogen because of its marked ability to develop resistance to last-line antibiotics. Carbapenem resistance may arise through chromosomal mutations, acquisition of resistance genes, and clonal dissemination under sustained antimicrobial pressure." - "OBJECTIVE: To investigate the temporal dynamics of carbapenem resistance in clinical P. aeruginosa isolates from a tertiary-care hospital in Valparaiso, Chile, and to assess their association with antimicrobial consumption." - "METHODS: Forty-five clinical isolates recovered between 2019 and 2024 were analysed. Antimicrobial susceptibility testing, phenotypic and molecular carbapenemase detection, motility and biofilm assays, and whole-genome sequencing were performed. Sequence types, resistome, virulome, and chromosomal mutations associated with resistance were characterized. Antimicrobial consumption data from the local stewardship programme were evaluated using temporal trend and cross-correlation analyses." - "RESULTS: Carbapenem non-susceptibility was frequent, and extensively drug-resistant isolates predominated during the pandemic and post-pandemic periods. Resistance was mainly associated with non-carbapenemase-producing isolates and was linked to mutations in oprD, regulators of the MexAB-OprM efflux system, and ampC-related pathways, together with intrinsic OXA-50-like-beta-lactamases. The blaVIM-2 gene was identified in ST408, ST815, and ST253. Temporal clonal turnover was observed, with ST309 emerging as the dominant lineage in 2023-2024. The acquired resistome diversified over time, whereas the virulome remained largely conserved. Higher antimicrobial consumption in intensive care units was associated with carbapenem resistance." - "CONCLUSIONS: Sustained antimicrobial pressure likely contributed to the persistence and replacement of carbapenem-resistant lineages. Integrating genomic surveillance with antimicrobial stewardship may improve detection and control of high-risk hospital clones."