{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T15:36:21Z","timestamp":1793547381200,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:00:00Z","timestamp":1696291200000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03AI144636"],"award-info":[{"award-number":["R03AI144636"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI151363"],"award-info":[{"award-number":["R21AI151363"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI104895"],"award-info":[{"award-number":["R01AI104895"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI151362"],"award-info":[{"award-number":["R21AI151362"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cefiderocol demonstrates excellent activity against MDR Pseudomonas aeruginosa; however, the activity against isolates from patients previously treated with \u03b2-lactam agents is unknown. We aimed to determine the activity of cefiderocol against P. aeruginosa collected before and after treatment with traditional \u03b2-lactams and new \u03b2-lactam\/\u03b2-lactamase inhibitors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Cefiderocol MICs were determined in triplicate in iron-depleted cation-adjusted Mueller\u2013Hinton broth and compared with \u03b2-lactam MICs tested by standard methods. All isolates underwent WGS analysis to identify mutations associated with resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>One hundred and seventy-eight P. aeruginosa isolates were evaluated; 48% (86\/178) were non-susceptible to ceftazidime\/avibactam, ceftolozane\/tazobactam and\/or imipenem\/relebactam. The cefiderocol MIC50 and MIC90 were 0.12 and 1\u2005mg\/L, respectively. Median cefiderocol MICs did not vary against isolates classified as MDR, XDR, or those non-susceptible to ceftazidime\/avibactam, ceftolozane\/tazobactam and\/or imipenem\/relebactam when compared with non-MDR isolates. Against isolates collected from patients previously treated with ceftolozane\/tazobactam, cefiderocol MICs were increased 4-fold compared with baseline. Cross-resistance to cefiderocol was identified in 21% (3\/14) of patients who developed treatment-emergent resistance to ceftolozane\/tazobactam. Overall, 6% (11\/178) of isolates demonstrated cefiderocol MICs \u22652\u2005mg\/L, which were disproportionately collected from patients previously treated with ceftolozane\/tazobactam (73%; 8\/11). Isolates with reduced cefiderocol susceptibility harboured mutations in ampC, tonB-dependent receptors, the response regulator pirR and ftsI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Cefiderocol demonstrates excellent in vitro activity against P. aeruginosa isolates exposed to other novel \u03b2-lactam agents; however, some exceptions were identified. Cross-resistance between cefiderocol and ceftolozane\/tazobactam was evident, but not with ceftazidime\/avibactam or imipenem\/relebactam. Reduced cefiderocol susceptibility was mediated by mutations in ampC and tonB-dependent receptors.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jacamr\/dlad107","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T11:15:58Z","timestamp":1696331758000},"source":"Crossref","is-referenced-by-count":43,"title":["<i>In vitro<\/i> activity of cefiderocol against <i>Pseudomonas aeruginosa<\/i> demonstrating evolved resistance to novel \u03b2-lactam\/\u03b2-lactamase inhibitors"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-5665","authenticated-orcid":false,"given":"Ryan K","family":"Shields","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Pittsburgh , Pittsburgh, PA , USA"},{"name":"Center for Innovative Antimicrobial Therapy, University of Pittsburgh , Pittsburgh, PA , USA"},{"name":"Antibiotic Management Program, University of Pittsburgh Medical Center , Pittsburgh, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen G","family":"Kline","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh , Pittsburgh, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M","family":"Squires","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh , Pittsburgh, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-0103","authenticated-orcid":false,"given":"Daria","family":"Van Tyne","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh , Pittsburgh, PA , USA"},{"name":"Center for Innovative Antimicrobial Therapy, University of Pittsburgh , Pittsburgh, PA , USA"},{"name":"Center for Evolutionary Biology and Medicine, University of Pittsburgh , Pittsburgh, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9620-2525","authenticated-orcid":false,"given":"Yohei","family":"Doi","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh , Pittsburgh, PA , USA"},{"name":"Center for Innovative Antimicrobial Therapy, University of Pittsburgh , Pittsburgh, PA , USA"},{"name":"Departments of Microbiology and Infectious Diseases, Fujita Health University School of Medicine , Toyoake, Aichi , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,3]]},"reference":[{"key":"2023100911590553700_dlad107-B1","article-title":"Multidrug-resistant Pseudomonas aeruginosa\u2014antibiotic resistance & patient safety portal","author":"CDC"},{"key":"2023100911590553700_dlad107-B2","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00642-17","article-title":"Identifying spectra of activity and therapeutic niches for ceftazidime-avibactam and imipenem-relebactam against carbapenem-resistant Enterobacteriaceae","volume":"61","author":"Haidar","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2023100911590553700_dlad107-B3","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/cid\/cix182","article-title":"Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa infections: clinical effectiveness and evolution of resistance","volume":"65","author":"Haidar","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2023100911590553700_dlad107-B4","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00084-21","article-title":"In vitro susceptibility of multidrug-resistant Pseudomonas aeruginosa following treatment-emergent resistance to ceftolozane-tazobactam","volume":"65","author":"Rubio","year":"2021","journal-title":"Antimicrob Agents 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for the treatment of carbapenem-resistant Gram-negative pathogens","volume":"15","author":"Karaiskos","year":"2019","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2023100911590553700_dlad107-B23","doi-asserted-by":"crossref","first-page":"e4472","DOI":"10.1093\/cid\/ciaa1909","article-title":"Evolution of cefiderocol non-susceptibility in Pseudomonas aeruginosa in a patient without previous exposure to the antibiotic","volume":"73","author":"Streling","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2023100911590553700_dlad107-B24","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1146\/annurev.micro.112408.134247","article-title":"TonB-dependent transporters: regulation, structure, and function","volume":"64","author":"Noinaj","year":"2010","journal-title":"Annu Rev Microbiol"},{"key":"2023100911590553700_dlad107-B25","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofab311","article-title":"Cefiderocol activity against clinical Pseudomonas aeruginosa 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