{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:56:11Z","timestamp":1792281371641,"version":"4.4.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to compare the stability of the newly developed \u03b2-lactams (cefiderocol) and \u03b2-lactam\/\u03b2-lactamase inhibitor combinations (ceftazidime\/avibactam, ceftolozane\/tazobactam, aztreonam\/avibactam, cefepime\/taniborbactam, cefepime\/zidebactam, imipenem\/relebactam, meropenem\/vaborbactam, meropenem\/nacubactam and meropenem\/xeruborbactam) against the most clinically relevant mechanisms of mutational and transferable \u03b2-lactam resistance in Pseudomonas aeruginosa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We screened a collection of 61 P. aeruginosa PAO1 derivatives. Eighteen isolates displayed the most relevant mechanisms of mutational resistance to \u03b2-lactams. The other 43 constructs expressed transferable \u03b2-lactamases from genes cloned in pUCP-24. MICs were determined by reference broth microdilution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cefiderocol and imipenem\/relebactam exhibited excellent in vitro activity against all of the mutational resistance mechanisms studied. Aztreonam\/avibactam, cefepime\/taniborbactam, cefepime\/zidebactam, meropenem\/vaborbactam, meropenem\/nacubactam and meropenem\/xeruborbactam proved to be more vulnerable to mutational events, especially to overexpression of efflux operons. The agents exhibiting the widest spectrum of activity against transferable \u03b2-lactamases were aztreonam\/avibactam and cefepime\/zidebactam, followed by cefepime\/taniborbactam, cefiderocol, meropenem\/xeruborbactam and meropenem\/nacubactam. However, some MBLs, particularly NDM enzymes, may affect their activity. Combined production of certain enzymes (e.g. NDM-1) with increased MexAB-OprM-mediated efflux and OprD deficiency results in resistance to almost all agents tested, including last options such as aztreonam\/avibactam and cefiderocol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cefiderocol and new \u03b2-lactam\/\u03b2-lactamase inhibitor combinations show promising and complementary in vitro activity against mutational and transferable P. aeruginosa \u03b2-lactam resistance. However, the combined effects of efflux pumps, OprD deficiency and efficient \u03b2-lactamases could still result in the loss of all therapeutic options. Resistance surveillance, judicious use of new agents and continued drug development efforts are encouraged.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkae263","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T16:56:41Z","timestamp":1721149001000},"page":"2591-2597","source":"Crossref","is-referenced-by-count":40,"title":["Impact of chromosomally encoded resistance mechanisms and transferable \u03b2-lactamases on the activity of cefiderocol and innovative \u03b2-lactam\/\u03b2-lactamase inhibitor combinations against\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8387-3784","authenticated-orcid":false,"given":"Luc\u00eda","family":"Gonz\u00e1lez-Pinto","sequence":"first","affiliation":[{"name":"Servicio de Microbiolog\u00eda & Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a , A Coru\u00f1a ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1681-969X","authenticated-orcid":false,"given":"Isaac","family":"Alonso-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda & Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a , A Coru\u00f1a ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1636-6429","authenticated-orcid":false,"given":"Tania","family":"Blanco-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda & Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a , A Coru\u00f1a 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