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In all, 57 clinical isolates co-producing two carbapenemases collected from Spanish hospitals during the period 2017\u20132022 were analyzed. Minimum inhibitory concentration (MIC) values for ceftazidime, ceftazidime\/avibactam, aztreonam, aztreonam\/avibactam, aztreonam\/nacubactam, cefiderocol, cefepime, cefepime\/taniborbactam, cefepime\/zidebactam, cefepime\/nacubactam, imipenem, imipenem\/relebactam, meropenem, meropenem\/vaborbactam, meropenem\/xeruborbactam, and meropenem\/ANT3310 were determined by reference broth microdilution. Genetic drivers of resistance were analyzed by whole-genome sequencing (WGS). The collection covered nine carbapenemase associations: VIM + OXA-48 (21\/57), NDM + OXA-48 (11\/57), KPC + VIM (10\/57), KPC + OXA-48 (6\/57), IMP + OXA-48 (3\/57), NDM + KPC (2\/57), NDM + VIM (2\/57), NDM + GES (1\/57), and KPC + IMP (1\/57). Ceftazidime\/avibactam, imipenem\/relebactam, and meropenem\/vaborbactam were the least active options. Aztreonam\/avibactam and aztreonam\/nacubactam were active against the whole collection and yielded MIC\n                      <jats:sub>50<\/jats:sub>\n                      \/MIC\n                      <jats:sub>90<\/jats:sub>\n                      values of \u22640.25\/0.5 mg\/L and 1\/2 mg\/L, respectively. Cefepime\/zidebactam (56\/57 susceptible), meropenem\/xeruborbactam (56\/57 susceptible), cefepime\/nacubactam (55\/57 susceptible), and cefiderocol (53\/57 susceptible) were also highly active, with MIC\n                      <jats:sub>50<\/jats:sub>\n                      \/MIC\n                      <jats:sub>90<\/jats:sub>\n                      values ranging from \u22640.25\u20132 mg\/L to 2\u20134 mg\/L, respectively. Meropenem\/ANT3310 (MIC\n                      <jats:sub>50<\/jats:sub>\n                      \/MIC\n                      <jats:sub>90<\/jats:sub>\n                      = 0.5\/\u226564 mg\/L; 47\/57 susceptible) and cefepime\/taniborbactam (MIC\n                      <jats:sub>50<\/jats:sub>\n                      \/MIC\n                      <jats:sub>90<\/jats:sub>\n                      = 0.5\/16 mg\/L; 44\/57 susceptible) also retained high levels of activity, although they were affected by NDM-type enzymes in combination with porin deficiency. Our findings highlight that cefiderocol and combinations of \u03b2-lactams and the novel \u03b2-lactamase inhibitors avibactam, nacubactam, taniborbactam, zidebactam, xeruborbactam, and ANT3310 show promising activity against double-carbapenemase-producing Enterobacterales.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00924-24","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T09:00:27Z","timestamp":1728464427000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Assessment of the activity and mechanisms of resistance to cefiderocol and combinations of \u03b2-lactams and the novel \u03b2-lactamase inhibitors avibactam, taniborbactam, zidebactam, nacubactam, xeruborbactam, and ANT3310 in emerging double-carbapenemase-producing Enterobacterales"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1636-6429","authenticated-orcid":false,"given":"Tania","family":"Blanco-Mart\u00edn","sequence":"first","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica e Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"L\u00f3pez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Referencia para tipado molecular y detecci\u00f3n de mecanismos de resistencia a antimicrobianos de Andaluc\u00eda (PIRASOA). Unidad de Gesti\u00f3n Cl\u00ednica de Microbiolog\u00eda y Enfermedades Infecciosas, Hospital Universitario Virgen Macarena. Instituto de Biomedicina de Sevilla (IBIS), CSIC, Universidad de Sevilla, Seville, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"Aracil","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Laboratorio de Referencia e Investigaci\u00f3n en Resistencia a Antibi\u00f3ticos e Infecciones relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Gonz\u00e1lez-Pinto","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica e Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Aja-Macaya","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica e Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Alonso-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica e Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salud","family":"Rodr\u00edguez-Pallares","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica e Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"S\u00e1nchez-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica e Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Outeda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica e Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"P\u00e9rez-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Laboratorio de Referencia e Investigaci\u00f3n en Resistencia a Antibi\u00f3ticos e Infecciones relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"V\u00e1zquez-Ucha","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica e Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6340-7815","authenticated-orcid":true,"given":"Alejandro","family":"Beceiro","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica e Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Pascual","sequence":"additional","affiliation":[{"name":"Laboratorio de Referencia para tipado molecular y detecci\u00f3n de mecanismos de resistencia a antimicrobianos de Andaluc\u00eda (PIRASOA). 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