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Phenotypic profile and molecular mechanism of resistance in carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa isolates from Brazilian hospitals

dc.contributor.authorKurtz, Pedro
dc.contributor.authorDel Peloso, Pedro F.
dc.contributor.authorPribul, Bruno Rocha
dc.contributor.authorAlbuquerque, Arthur M.
dc.contributor.authorAntunes, Bianca B.P.
dc.contributor.authorRamos, Grazielle Vianna
dc.contributor.authorBozza, Fernando A.
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionComprehensive Health Research Centre (CHRC) - pólo NMS
dc.contributor.pblFrontiers Research Foundation
dc.date.accessioned2026-01-14T15:52:14Z
dc.date.available2026-01-14T15:52:14Z
dc.date.issued2025-11
dc.descriptionPublisher Copyright: Copyright © 2025 Kurtz, Del Peloso, Pribul, Albuquerque, Antunes, Ramos and Bozza.
dc.description.abstractBackground/Objectives: Carbapenemase-producing Enterobacterales and P. aeruginosa are critical threats to global public health, especially in high-burden regions such as Brazil. Imipenem-relebactam (IMR), a combination of a carbapenem with a β-lactamase inhibitor, is a promising treatment option against resistant Gram-negative bacteria. This study aimed to characterize phenotypic resistance and molecular mechanisms in clinical isolates from Brazilian hospitals and assess IMR activity. Methods: A prospective multicenter study was conducted across 12 hospitals in Rio de Janeiro. A total of 150 Enterobacterales and 100 P. aeruginosa isolates resistant to carbapenems were collected. Isolates were identified by MALDI-TOF and screened for carbapenemase genes (KPC, NDM, VIM, IMP, OXA-48) using PCR. Susceptibility to IMR was determined by broth microdilution following EUCAST guidelines. Next-generation sequencing (NGS) was performed on a subset of multidrug-resistant isolates. Results: IMR resistance was identified in 34.5% of K. pneumoniae and 74% of P. aeruginosa isolates. Among Enterobacterales, 21.1% of KPC-producers and 88.9% of OXA-48-producers were resistant to IMR. The bla_KPC gene was predominant, but NDM was increasingly detected. In P. aeruginosa, resistance was largely unrelated to carbapenemase production, implicating porin loss and efflux pumps. NGS revealed extensive co-resistance and multiple virulence genes in K. pneumoniae isolates. Conclusion: This study highlights the emergence of significant resistance to imipenem-relebactam in Brazil, driven by both enzymatic and non-enzymatic mechanisms. Ongoing molecular surveillance and tailored treatment strategies are essential to address the evolving threat of multidrug-resistant Gram-negative infections in endemic regions.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent280952
dc.identifier.doi10.3389/fmicb.2025.1689777
dc.identifier.issn1664-302X
dc.identifier.otherPURE: 147373702
dc.identifier.otherPURE UUID: 634b0826-8a24-4e9a-a145-7befcd3487ef
dc.identifier.otherScopus: 105023680635
dc.identifier.urihttp://hdl.handle.net/10362/199003
dc.identifier.urlhttps://www.scopus.com/pages/publications/105023680635
dc.language.isoeng
dc.peerreviewedyes
dc.subjectantimicrobial therapy
dc.subjectcarbapenemase
dc.subjectgram-negative
dc.subjectimipenem-relebactam
dc.subjectmulti-drug resistant
dc.subjectMicrobiology
dc.subjectMicrobiology (medical)
dc.subjectSDG 3 - Good Health and Well-being
dc.titlePhenotypic profile and molecular mechanism of resistance in carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa isolates from Brazilian hospitalsen
dc.title.subtitleimplications for the introduction of imipenem-relebactamen
dc.typejournal article
degois.publication.titleFrontiers in Microbiology
degois.publication.volume16
dspace.entity.typePublication
rcaap.rightsopenAccess

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