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We aimed to evaluate its activity in combination with meropenem and compare it with other \u03b2-lactam\/\u03b2-lactamase inhibitor combinations against Enterobacterales. The following isolates were screened: (i) an isogenic collection of 94\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      isolates producing \u03b2-lactamases under wild-type and low-permeability conditions, (ii) 300 genetically diverse clinical Enterobacterales isolates producing the three main carbapenemase types (KPC-like, OXA-48-like, and metallo-\u03b2-lactamases), and (iii) two collections of isolates producing mechanisms of resistance to \u03b2-lactam\/\u03b2-lactamase inhibitor combinations, such as KPC variants or PBP3 insertions combined with metallo-\u03b2-lactamases (MBLs). The MICs of meropenem, meropenem\/xeruborbactam, meropenem\/vaborbactam, imipenem, imipenem\/relebactam, cefepime, cefepime\/taniborbactam, ceftazidime, ceftazidime\/avibactam, aztreonam, and aztreonam\/avibactam were determined by reference broth microdilution and interpreted following the European Committee on Antimicrobial Susceptibility Testing guidelines, using the breakpoint of the \u03b2-lactam alone for not yet approved combinations. Resistance mechanisms of all clinical isolates were analyzed by whole genome sequencing. Meropenem\/xeruborbactam had the broadest spectrum against the isogenic collection, although higher MICs were noted for transformants producing IMP-23, SPM-1, and NDM enzymes (these latter only when produced under low-permeability conditions). Meropenem\/xeruborbactam displayed the most potent activity against the collection of 300 clinical strains (MIC\n                      <jats:sub>50\/90<\/jats:sub>\n                      \u22640.06\/\u22640.06 mg\/L). Xeruborbactam restored meropenem activity against the strains carrying resistance mechanisms to \u03b2-lactam\/\u03b2-lactamase inhibitor combinations, including strains producing KPC variants or MBLs in combination with additional chromosomal alterations (MIC range: \u22640.06\u20130.25 and \u22640.06\u20134 mg\/L, respectively). Our findings highlight the potential of xeruborbactam in combination with meropenem as a promising treatment against carbapenemase-producing Enterobacterales, including strains with emerging resistance to other \u03b2-lactam\/\u03b2-lactamase inhibitor combinations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00533-25","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T14:17:46Z","timestamp":1753453066000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Broad spectrum of \u03b2-lactamase coverage and potent antimicrobial activity of xeruborbactam in combination with meropenem against carbapenemase-producing Enterobacterales, including strains resistant to new \u03b2-lactam\/\u03b2-lactamase inhibitor combinations"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5696-5812","authenticated-orcid":false,"given":"Luc\u00eda","family":"S\u00e1nchez-Pe\u00f1a","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/044knj408","id-type":"ROR","asserted-by":"publisher"}],"name":"Servicio de Microbiolog\u00eda Cl\u00ednica, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a","place":["A Coru\u00f1a, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8270-0259","authenticated-orcid":false,"given":"Salud","family":"Rodr\u00edguez-Pallares","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/044knj408","id-type":"ROR","asserted-by":"publisher"}],"name":"Servicio de Microbiolog\u00eda Cl\u00ednica, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A 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