{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:40:52Z","timestamp":1790962852189,"version":"4.1.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"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":[[2025,11,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cefepime-induced neurotoxicity (CIN) is commonly described but neurotoxic concentration threshold remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>This single-center prospective study included patients with febrile neutropenia treated by continuous infusion of cefepime in the hematology department. Both cefepime steady-state concentrations measurement (Css) and neurological assessment were performed at defined timepoints during the first 10 days after the onset of cefepime. Cefepime imputability was determined for each neurological event. The main objective was to assess the relationship between plasma cefepime exposure and the occurrence of neurotoxicity. Secondary objectives were to establish a cefepime Css threshold discriminating CIN and control group and identify influencing covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>One hundred and thirty-four patients were analyzed (346Css). CIN occurred in 9.7% of the cases (14\/145 courses). Maximal Css were not significantly different between the 2 groups (53.2 \u00b1 31.3 vs 39.5 \u00b1 13.3\u2005mg\/L). Median neurotoxicity onset was 5 days. After multivariable analysis, both concomitant chimeric antigen receptor T-cell administration and each mg\/mL increase in cefepime Css were independently associated with CIN onset (odds ratio 19.7 [5.6\u201369.1] and 1.030 [1.005\u20131.056], P &amp;lt; .001 and P = .020), respectively. Receiver operating characteristic curve analysis identified an adjusted threshold concentration of 36.7\u2005mg\/L (sensitivity 89%, specificity 90%) to differentiate the 2 groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides real-life data on CIN using a multidisciplinary approach. Cefepime exposure was found to be independently associated with the occurrence of neurotoxicity together with chimeric antigen receptor T-cell therapy. The neurotoxicity threshold of 36.7\u2005mg\/L confirms a lower toxicity threshold than for other \u03b2 lactams, offering an additional tool for the management of high-dose cefepime therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf205","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T07:50:56Z","timestamp":1749109856000},"page":"721-727","source":"Crossref","is-referenced-by-count":5,"title":["Cefepime Concentration-Toxicity Relationship in Hematological Patients Treated With Continuous Infusion: A Prospective Study"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-1030","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Lalanne","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) UMR_S 1085 , Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-No\u00eblle","family":"Osmont","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) UMR_S 1085 , Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Triquet","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) UMR_S 1085 , Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Morcet","sequence":"additional","affiliation":[{"name":"CIC-P 1414 Clinical Investigation Center, Inserm , Rennes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Marchand","sequence":"additional","affiliation":[{"name":"Hematology Department, CHU de Rennes , Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roch","family":"Houot","sequence":"additional","affiliation":[{"name":"Hematology Department, CHU de Rennes , Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Polard","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) UMR_S 1085 , Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6595-8154","authenticated-orcid":false,"given":"Marie-Cl\u00e9mence","family":"Verdier","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) UMR_S 1085 , Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-3629","authenticated-orcid":false,"given":"Florian","family":"Lemaitre","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) UMR_S 1085 , Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"2025110901580241000_ciaf205-B1","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1086\/383050","article-title":"Management of fever in neutropenic patients with different risks of complications","volume":"39","author":"Klastersky","year":"2004","journal-title":"Clin Infect Dis"},{"key":"2025110901580241000_ciaf205-B2","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1200\/JCO.2017.77.6211","article-title":"Outpatient management of fever and 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