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We determine the activity of cefiderocol and comparators in a collection of 154 P. aeruginosa isolates recovered from pwCF during three multicentre studies performed in 17 Spanish hospitals in 2013, 2017 and 2021.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>ISO broth microdilution was performed and MICs were interpreted with CLSI and EUCAST criteria. Mutation frequency and WGS were also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 21.4% were MDR, 20.8% XDR and 1.3% pandrug-resistant (PDR). Up to 17% of the isolates showed a hypermutator phenotype. Cefiderocol demonstrated excellent activity; only 13 isolates (8.4%) were cefiderocol resistant by EUCAST (none using CLSI). A high proportion of the isolates resistant to ceftolozane\/tazobactam (71.4%), meropenem\/vaborbactam (70.0%), imipenem\/relebactam (68.0%) and ceftazidime\/avibactam (55.6%) were susceptible to cefiderocol. Nine out of 13 cefiderocol-resistant isolates were hypermutators (P\u200a&amp;lt;\u200a0.001). Eighty-three STs were detected, with ST98 being the most frequent. Only one isolate belonging to the ST175 high-risk clone carried blaVIM-2. Exclusive mutations affecting genes involved in membrane permeability, AmpC overexpression (L320P-AmpC) and efflux pump up-regulation were found in cefiderocol-resistant isolates (MIC\u200a=\u200a4\u20138\u2005mg\/L). Cefiderocol resistance could also be associated with mutations in genes related to iron uptake (tonB-dependent receptors and pyochelin\/pyoverdine biosynthesis).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results position cefiderocol as a therapeutic option in pwCF infected with P. aeruginosa resistant to most recent \u03b2-lactam\/\u03b2-lactamase inhibitor combinations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkae126","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T19:22:01Z","timestamp":1712949721000},"page":"1432-1440","source":"Crossref","is-referenced-by-count":15,"title":["<i>In vitro<\/i>\n                    activity of cefiderocol in\n                    <i>Pseudomonas aeruginosa<\/i>\n                    isolates from people with cystic fibrosis recovered during three multicentre studies in Spain"],"prefix":"10.1093","volume":"79","author":[{"given":"Ainhize","family":"Maruri-Aransolo","sequence":"first","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"L\u00f3pez-Causap\u00e9","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario de Son Espases and (IdISBa) , Palma de Mallorca , Spain"},{"name":"CIBER de Enfermedades Infecciosas CIBERINFEC, Instituto de Salud Carlos III , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2857-2572","authenticated-orcid":false,"given":"Marta","family":"Hern\u00e1ndez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) , Madrid , Spain"},{"name":"CIBER de Enfermedades Infecciosas CIBERINFEC, Instituto de Salud Carlos III , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Garc\u00eda-Castillo","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan de Dios","family":"Caballero-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) , Madrid , Spain"},{"name":"CIBER de Enfermedades Infecciosas CIBERINFEC, Instituto de Salud Carlos III , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Oliver","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario de Son Espases and (IdISBa) , Palma de Mallorca , Spain"},{"name":"CIBER de Enfermedades Infecciosas CIBERINFEC, Instituto de Salud Carlos III , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1675-3173","authenticated-orcid":false,"given":"Rafael","family":"Cant\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) , Madrid , Spain"},{"name":"CIBER de Enfermedades Infecciosas CIBERINFEC, Instituto de Salud Carlos III , Madrid , 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