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We evaluated the contribution of\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      resistance mechanisms to cefiderocol\/xeruborbactam susceptibility. A panel of 61\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">aeruginosa<\/jats:italic>\n                      PAO1 derivatives was tested, including 20 knockout mutants representing key chromosomal resistance mechanisms (e.g.,\n                      <jats:italic toggle=\"yes\">ampC<\/jats:italic>\n                      overexpression, efflux upregulation, porin loss, iron uptake deficiency) and 41 transformants producing major circulating \u03b2-lactamases. Xeruborbactam was assessed in combination with cefiderocol and cefepime at 4 and 8 mg\/L and compared with taniborbactam. Additionally, 99 cefiderocol-resistant clinical\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      isolates were evaluated. Cefiderocol\/xeruborbactam retained activity against most\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      mutants with chromosomally encoded resistance mechanisms. However, the\n                      <jats:italic toggle=\"yes\">P. aeruginosa piuC-<\/jats:italic>\n                      defective mutant yielded increased cefiderocol minimum inhibitory concentrations (MIC = 2 mg\/L), which could not be restored by xeruborbactam. Xeruborbactam significantly increased the activity of cefiderocol against the majority of\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      PAO1 transformants, including those producing PER-1, SHV-12, KPC \u03a9-loop mutants, or NDM variants. Cefiderocol\/xeruborbactam was active against IMP-type MBLs (which only weakly hydrolyze cefiderocol), including xeruborbactam-resistant enzymes. Relative to taniborbactam, xeruborbactam-based combinations showed similar activity against\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      PAO1 transformants, but with slightly higher MIC values when tested against metallo-\u03b2-lactamase producers. This MIC increase in xeruborbactam-based combinations was partly because of the constitutive MexAB-OprM efflux in the\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      background, as confirmed with\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      PAO1 efflux mutants. Importantly, xeruborbactam restored susceptibility in 78% of 99 cefiderocol-resistant\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      strains, reducing the MIC\n                      <jats:sub>90<\/jats:sub>\n                      from 64 to 4 mg\/L. Cefiderocol\/xeruborbactam shows promising activity against\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01048-25","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:18:49Z","timestamp":1761067129000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Contribution of mutational resistance mechanisms and acquired \u03b2-lactamases to cefiderocol\/xeruborbactam susceptibility in\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8387-3784","authenticated-orcid":false,"given":"Luc\u00eda","family":"Gonz\u00e1lez-Pinto","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/044knj408","id-type":"ROR","asserted-by":"publisher"}],"name":"Servicio de Microbiolog\u00eda Cl\u00ednica & Grupo de Investigaci\u00f3n en Microbiolog\u00eda, Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Sergas, Universidade da Coru\u00f1a (UDC)","place":["A Coru\u00f1a, Spain"]},{"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}],"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6042-5674","authenticated-orcid":false,"given":"Mar\u00eda 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