Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp

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dc.citation.titleMicrobiology Spectrum
dc.citation.volume13
dc.contributor.orcidhttps://orcid.org/0000-0002-4780-5311
dc.contributor.orcidhttps://orcid.org/0000-0001-5840-5869
dc.contributor.orcidhttps://orcid.org/0000-0003-0234-4643
dc.contributor.orcidhttps://orcid.org/0000-0002-6298-7811
dc.contributor.orcidhttps://orcid.org/0000-0002-3299-894X
dc.contributor.orcidhttps://orcid.org/0000-0002-9904-7890
dc.creatorWong, Olivia
dc.creatorMezcord, Vyanka
dc.creatorLopez, Christina
dc.creatorTraglia, German M.
dc.creatorPasteran, Fernando
dc.creatorTuttobene, Marisel Romina
dc.creatorCorso, Alejandra
dc.creatorTolmasky, Marcelo E.
dc.creatorBonomo, Robert A.
dc.creatorRamírez, María Soledad
dc.date.accessioned2025-02-28T13:05:40Z
dc.date.available2025-02-28T13:05:40Z
dc.date.issued2024-08-20
dc.description.abstractCefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections.
dc.description.filFil: Wong, Olivia. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies, Department of Biological Science; United States.
dc.description.filFil: Mezcord, Vyanka. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies, Department of Biological Science; United States.
dc.description.filFil: Lopez, Christina. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies, Department of Biological Science; United States.
dc.description.filFil: Traglia, German M. Universidad de la República. Unidad de Genómica y Bioinformática. Departamento de Ciencias Biológicas; Uruguay.
dc.description.filFil: Pasteran, Fernando. Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional/Regional de Referencia en Antimicrobianos; Argentina.
dc.description.filFil: Tuttobene, Marisel Romina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biología Molecular; Argentina.
dc.description.filFil: Tuttobene, Marisel Romina. Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET); Argentina.
dc.description.filFil: Corso, Alejandra. Universidad de la República. Unidad de Genómica y Bioinformática. Departamento de Ciencias Biológicas; Uruguay.
dc.description.filFil: Tolmasky, Marcelo E. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies, Department of Biological Science; United States.
dc.description.filFil: Bonomo, Robert A. Research Service and GRECC. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; United States.
dc.description.filFil: Bonomo, Robert A. Louis Stokes Veterans Affairs Medical Center. Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics; United States.
dc.description.filFil: Bonomo, Robert A. CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology; United States.
dc.description.filFil: Ramírez, María Soledad. California State University Fullerton. College of Natural Sciences and Mathematics. Center for Applied Biotechnology Studies, Department of Biological Science; United States.
dc.description.sponsorshipNational Institutes of Health (NIH): SG3GM125556, R01AI100560, R01AI072219, R01AI063517, 2R15 AI047115
dc.description.sponsorshipCleveland Department of Veterans Affairs: 1101BX001974
dc.format.extent1-11
dc.identifier.citationWong O, Mezcord V, Lopez C, Traglia GM, Pasteran F, Tuttobene MR, Corso A, Tolmasky ME, Bonomo RA, Ramirez MS. 2024. Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp.. Microbiol Spectr 12:e00930-24. https://doi.org/10.1128/spectrum.00930-24
dc.identifier.issn2165-0497
dc.identifier.urihttps://hdl.handle.net/2133/28979
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.relation.publisherversionhttps://journals.asm.org/doi/pdf/10.1128/spectrum.00930-24
dc.relation.publisherversionhttps://doi.org/10.1128/spectrum.00930-24
dc.rightsopenAccess
dc.rights.holderWong, Olivia
dc.rights.holderMezcord, Vyanka
dc.rights.holderLopez, Christina
dc.rights.holderTraglia, German M.
dc.rights.holderPasteran, Fernando
dc.rights.holderTuttobene, Marisel Romina
dc.rights.holderCorso, Alejandra
dc.rights.holderTolmasky, Marcelo E.
dc.rights.holderBonomo, Robert A.
dc.rights.holderRamírez, María Soledad
dc.rights.textAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAcinetobacter
dc.subjectAntagonism
dc.subjectCefiderocol
dc.subjectAntimicrobial susceptibility testing (AST)
dc.subjectAvibactam
dc.subjectSulbactam
dc.subjectCarbapenem-resistance
dc.titleHetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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