{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T18:14:51Z","timestamp":1776708891883,"version":"3.51.2"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and objectives<\/jats:title>\n                  <jats:p>Cefiderocol approved dosages are based on a prolonged infusion (PI) of 3\u2005h that may not be adequate in all settings The objective of this study was to identify alternative cefiderocol dosage regimens based on short infusion (SI) or continuous infusion (CI).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed 1000-patient pharmacokinetic\/pharmacodynamic (PK\/PD) simulations based on a reference population model. Drug penetration into the epithelial lining fluid (ELF) was considered for pneumonia. For various stages of creatinine clearance (CLCR), we simulated the recommended PI as well as various SI (1\u2005h-infusion) and CI regimens. The PK\/PD targets were set at 75% or 100% of the dosing interval during which the free concentration of cefiderocol was above the MIC (fT\u200a&amp;gt;\u200aMIC) in plasma and ELF. The PTAs were computed considering the cefiderocol MIC breakpoint (2\u2005mg\/L).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In plasma, all recommended PI regimens were associated with a PTA \u200a\u2265\u200a90%. Some SI regimens also showed acceptable PTAs. CI regimens were associated with high PTAs, even for doses as low as 2\u2005g over 24\u2005h and in patients with high CLCR. Recommended dosages failed to achieve acceptable PTAs in ELF for the 100% fT\u200a&amp;gt;\u200aMIC target in patients with CLCR\u200a \u2265\u200a90\u2005mL\/min. CI regimens showed the highest PTAs for the high target, but high doses of 6 to 8\u2005g over 24\u2005h were required in patients with CLCR\u200a \u2265\u200a90\u2005mL\/min.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We identified SI and CI regimens of cefiderocol that may be useful alternatives to the PI regimens in some patients. Continuous administration of cefiderocol may be especially relevant for patients with pneumonia. However, further clinical evaluation is necessary.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae464","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T05:21:27Z","timestamp":1734931287000},"page":"726-730","source":"Crossref","is-referenced-by-count":6,"title":["Optimal dosage regimens of cefiderocol administered by short, prolonged or continuous infusion: a PK\/PD simulation study"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-2932","authenticated-orcid":false,"given":"Sylvain","family":"Goutelle","sequence":"first","affiliation":[{"name":"Service de Pharmacie, Hospices Civils de Lyon, GH Nord, H\u00f4pital de la Croix-Rousse , Lyon ,","place":["France"]},{"name":"UMR CNRS 5558, Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive, Univ Lyon, Universit\u00e9 Claude Bernard Lyon 1 , Villeurbanne ,","place":["France"]},{"name":"Facult\u00e9s de M\u00e9decine et de Pharmacie de Lyon, Univ Lyon, Universit\u00e9 Claude Bernard Lyon 1 , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najib","family":"Ammour","sequence":"additional","affiliation":[{"name":"Service de Pharmacie, Hospices Civils de Lyon, GH Nord, H\u00f4pital de la Croix-Rousse , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan","family":"Ferry","sequence":"additional","affiliation":[{"name":"UMR CNRS 5558, Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive, Univ Lyon, Universit\u00e9 Claude Bernard Lyon 1 , Villeurbanne ,","place":["France"]},{"name":"Facult\u00e9s de M\u00e9decine et de Pharmacie de Lyon, Univ Lyon, Universit\u00e9 Claude Bernard Lyon 1 , Lyon ,","place":["France"]},{"name":"Service des Maladies Infectieuses et Tropicales, Centre de R\u00e9f\u00e9rence pour la prise en charge des Infections Ost\u00e9o-Articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Groupement Hospitalier Nord, H\u00f4pital de la Croix-Rousse , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Schramm","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, FMTS-CHRU Strasbourg, University of Strasbourg , Strasbourg F67000 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Lepeule","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Transversale de Traitement des Infections, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pitaux Universitaires Henri Mondor , Cr\u00e9teil F-94010 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4687-2173","authenticated-orcid":false,"given":"Arnaud","family":"Friggeri","sequence":"additional","affiliation":[{"name":"Facult\u00e9s de M\u00e9decine et de Pharmacie de Lyon, Univ Lyon, Universit\u00e9 Claude Bernard Lyon 1 , Lyon ,","place":["France"]},{"name":"Services d\u2019Anesth\u00e9sie-R\u00e9animation M\u00e9decine Intensive, Hospices Civils de Lyon, GH Sud , Lyon ,","place":["France"]},{"name":"Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Univ Lyon, Universit\u00e9 Claude Bernard Lyon 1 , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"2025030423053829700_dkae464-B1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s40265-019-1055-2","article-title":"Cefiderocol: a siderophore cephalosporin with activity against carbapenem-resistant and multidrug-resistant Gram-negative Bacilli","volume":"79","author":"Zhanel","year":"2019","journal-title":"Drugs"},{"key":"2025030423053829700_dkae464-B2","doi-asserted-by":"publisher","first-page":"e01437","DOI":"10.1128\/AAC.01437-20","article-title":"Population pharmacokinetic and pharmacokinetic\/pharmacodynamic analyses of cefiderocol, a parenteral siderophore cephalosporin, in patients with pneumonia, bloodstream infection\/sepsis, or complicated urinary tract infection","volume":"65","author":"Kawaguchi","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2025030423053829700_dkae464-B3","doi-asserted-by":"publisher","first-page":"S552","DOI":"10.1093\/cid\/ciz828","article-title":"Pharmacokinetic and pharmacodynamic profiles of cefiderocol, a novel siderophore cephalosporin","volume":"69","author":"Katsube","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2025030423053829700_dkae464-B4","doi-asserted-by":"publisher","first-page":"e00700","DOI":"10.1128\/AAC.00700-17","article-title":"Efficacy of cefiderocol against carbapenem-resistant Gram-negative bacilli in immunocompetent-rat respiratory tract infection models recreating human plasma pharmacokinetics","volume":"61","author":"Matsumoto","year":"2017","journal-title":"Antimicrob 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