{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:22:14Z","timestamp":1784164934525,"version":"3.55.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To characterize a carbapenem-resistant Citrobacter freundii (Cf-Emp) co-producing class A, B and D carbapenemases, resistant to novel \u03b2-lactamase inhibitor combinations (BLICs) and cefiderocol.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Carbapenemase production was tested by an immunochromatography assay. Antibiotic susceptibility testing (AST) was performed by broth microdilution. WGS was performed using short- and long-read sequencing. Transfer of carbapenemase-encoding plasmids was assessed by conjugation experiments.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Cf-Emp was isolated on selective medium for carbapenem-resistant Enterobacterales from the surveillance rectal swab taken at hospital admission from a patient of Moroccan origin. Cf-Emp produced three different carbapenemases, including KPC-2, OXA-181 and VIM-1, and was resistant to all \u03b2-lactams including carbapenems, novel BLICs (ceftazidime\/avibactam, meropenem\/vaborbactam and imipenem\/relebactam) and cefiderocol. MIC of aztreonam\/avibactam was 0.25 mg\/L. The strain belonged to ST22, one of the C. freundii lineages of global diffusion, known to be associated with carbapenemase production. Each carbapenemase gene was located aboard a different plasmid (named pCf-KPC, pCf-OXA and pCf-VIM, respectively), which also carried other clinically relevant resistance genes, such as armA (pCf-KPC), blaSHV-12 (pCf-VIM) and qnrS1 (pCf-OXA). Transferability to Escherichia coli J53 by conjugation was observed for all plasmids.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The finding of enterobacterial strains carrying multiple carbapenemase genes on transferable plasmids is alarming, because similar strains could provide an important reservoir for disseminating these clinically relevant resistance determinants.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad150","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T21:16:15Z","timestamp":1684530975000},"page":"1677-1682","source":"Crossref","is-referenced-by-count":10,"title":["<i>Citrobacter freundii<\/i> resistant to novel \u03b2-lactamase inhibitor combinations and cefiderocol, co-producing class A, B and D carbapenemases encoded by transferable plasmids"],"prefix":"10.1093","volume":"78","author":[{"given":"Eleonora","family":"Riccobono","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence , Florence , Italy"},{"name":"Department of Medical Biotechnologies, University of Siena , Siena , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Salvetti","sequence":"additional","affiliation":[{"name":"Microbiology Unit, San Giuseppe Hospital, Empoli , Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Coppi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence , Florence , Italy"},{"name":"Clinical Microbiology and Virology Unit, Careggi University Hospital , Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"Montenora","sequence":"additional","affiliation":[{"name":"Microbiology Unit, San Giuseppe Hospital, Empoli , Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5863-5805","authenticated-orcid":false,"given":"Vincenzo","family":"Di Pilato","sequence":"additional","affiliation":[{"name":"Clinical Microbiology and Virology Unit, Careggi University Hospital , Florence , Italy"},{"name":"Department of Surgical Sciences and Integrated Diagnostics, University of Genoa , Genoa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Maria","family":"Rossolini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence , Florence , Italy"},{"name":"Clinical Microbiology and Virology Unit, Careggi University Hospital , Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"2023070504554655700_dkad150-B1","doi-asserted-by":"crossref","first-page":"823684","DOI":"10.3389\/fcimb.2022.823684","article-title":"Global threat of carbapenem-resistant Gram-negative bacteria","volume":"12","author":"Jean","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"2023070504554655700_dkad150-B2","doi-asserted-by":"crossref","first-page":"e00047-19","DOI":"10.1128\/CMR.00047-19","article-title":"Epidemiology of \u03b2-lactamase-producing pathogens","volume":"33","author":"Bush","year":"2020","journal-title":"Clin Microbiol Rev"},{"key":"2023070504554655700_dkad150-B3","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.3201\/eid2709.210456","article-title":"Gram-negative bacteria harboring multiple carbapenemase genes, United States, 2012-2019","volume":"27","author":"Ham","year":"2021","journal-title":"Emerg Infect Dis"},{"key":"2023070504554655700_dkad150-B4","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1093\/jac\/dkac005","article-title":"Characterization of VIM-1-, NDM-1- and OXA-48-producing Citrobacter freundii in France","volume":"77","author":"Biez","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2023070504554655700_dkad150-B5","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1128\/AAC.01305-10","article-title":"Extremely drug-resistant Citrobacter freundii isolate producing NDM-1 and other carbapenemases identified in a patient returning from India","volume":"55","author":"Poirel","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"2023070504554655700_dkad150-B6","author":"The European Committee on Antimicrobial Susceptibility Testing (EUCAST). 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