{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:50:46Z","timestamp":1791845446738,"version":"4.3.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"IAME"},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["DEQ20161136698"],"award-info":[{"award-number":["DEQ20161136698"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR20-PAMR-0001"],"award-info":[{"award-number":["ANR20-PAMR-0001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Cefiderocol is a siderophore cephalosporin active in vitro against carbapenemase-producing Enterobacterales, including New Delhi metallo-\u03b2-lactamases (NDM-1). A significant impact of the size of bacterial inoculum on its efficacy has been described in vitro, the clinical impact of which is unclear. Here, we analyse the inoculum effect of cefiderocol against E. coli-NDM-1 in vitro and in a murine peritonitis model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>Escherichia coli 62-pTOPO and its isogenic variant expressing NDM-1, 62-pTOPO-NDM, were constructed from a clinical strain. MICs and bactericidal kinetics were determined at standard (105\u2005cfu\/mL) and high inoculum (107\u2005cfu\/mL). The in vivo effect was assessed in a severe murine peritonitis model, comparing low (106\u2005cfu\/mL) and high (108\u2005cfu\/mL) inoculum. Survival rates, organ sterilization and bacterial counts in spleen and peritoneal fluid were compared.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Cefiderocol MICs for 62-pTOPO and 62-pTOPO-NDM at standard and high inoculum were 0.008, 2, 2 and 1024\u2005mg\/L, respectively. Bactericidal activity was not achieved in vitro for 62-pTOPO-NDM at high inoculum with high cefiderocol concentrations (16\u2005mg\/L). In vivo, for 62-pTOPO-NDM, no difference was found in survival, organ sterilization or bacterial counts between low and high inoculum. For 62-pTOPO, no difference was observed in survival, despite less organ sterilization and higher bacterial counts in organs with the high inoculum.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>A significant inoculum effect of cefiderocol was observed in vitro for 62-pTOPO and 62-pTOPO-NDM. However, the effectiveness of cefiderocol was not reduced in vivo with a high bacterial inoculum. In vitro inoculum effect of cefiderocol may not be clinically significant.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae368","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T16:27:31Z","timestamp":1729614451000},"page":"3323-3331","source":"Crossref","is-referenced-by-count":4,"title":["Inoculum effect of cefiderocol against NDM-1 producing <i>Escherichia coli in vitro<\/i> and in a murine model of peritonitis"],"prefix":"10.1093","volume":"79","author":[{"given":"Anne-Sophie","family":"Godron","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Universit\u00e9 Sorbonne Paris Nord, Inserm, IAME , Paris 75018 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Amoura","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Universit\u00e9 Sorbonne Paris Nord, Inserm, IAME , Paris 75018 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pharmacologie, H\u00f4pital Avicenne, AP-HP , Bobigny F-93000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s B","family":"Jousset","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Service de bact\u00e9riologie-hygi\u00e8ne and French National Reference Center for Antibiotic Resistance, H\u00f4pital Bic\u00eatre, AP-HP , Le Kremlin-Bic\u00eatre F-94275 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Jullien","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Universit\u00e9 Sorbonne Paris Nord, Inserm, IAME , Paris 75018 ,","place":["France"]},{"name":"Universit\u00e9 Paris-Saclay, Service de bact\u00e9riologie-hygi\u00e8ne and French National Reference Center for Antibiotic Resistance, H\u00f4pital Bic\u00eatre, AP-HP , Le Kremlin-Bic\u00eatre F-94275 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