{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:23:32Z","timestamp":1785421412205,"version":"3.56.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      High-dose continuous infusion of cefepime is frequently employed in ICU patients with a creatinine clearance above 60 mL\/min. The CEFTOX study aimed to investigate whether this regimen could lead to cefepime overexposure and cefepime-induced neurotoxicity (CIN) in a cohort of severe trauma and brain-injured patients. This retrospective cohort study included patients from a Level 1 Trauma Center who received a continuous infusion of 6 g\/day of cefepime and had a therapeutic drug monitoring (TDM) within 24\u201348 h of treatment initiation. They were divided into three groups based on creatinine clearance: mild renal impairment (60\u201390 mL\/min), normal clearance (90\u2013150 mL\/min), and augmented renal clearance (ARC) (&gt;150 mL\/min). The primary outcome was cefepime overexposure. A key secondary outcome was CIN. One hundred and sixty-two critically ill patients were included: 84 with ARC, 62 with normal renal clearance, and 16 with mild renal impairment. Cefepime overexposure occurred in 72 (44.4%) patients. While 50% of patients with normal renal clearance experienced overexposure, the rate was higher in those with mild renal impairment (87.5%) and lower in those with ARC (32.1%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.0001). In the ARC group, age &gt; 33 years was a risk factor for overexposure (odds ratio [OR] 3.76; 95% CI [1.30\u201310.95];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.01), while sepsis was a protective factor (OR 0.30; 95% CI [0.11\u20130.83];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.02). CIN was observed in 24% of overexposed patients when TDM results were obtained \u226448 h compared to 57.4% when results were delayed &gt;48 h (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.006). These results highlight the need for early TDM and individualized dose adjustment to avoid CIN.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01735-25","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:00:14Z","timestamp":1770904814000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Safety concerns associated with high-dose continuous infusion of cefepime among critically ill patients with mild renal impairment to augmented renal clearance at a level 1 trauma center: CEFTOX study"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2810-443X","authenticated-orcid":true,"given":"Myriam","family":"Lamamri","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jyzk483","id-type":"ROR","asserted-by":"publisher"}],"name":"D\u00e9partement d'Anesth\u00e9sie R\u00e9animation, AP-HP, H\u00f4pital Beaujon, DMU PARABOL","place":["Clichy, France"]},{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"NeuroDiderot, Neuroprotection of the Developing Brain, Universit\u00e9 Paris Cit\u00e9, INSERM UMR-S 1141","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Rutman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jyzk483","id-type":"ROR","asserted-by":"publisher"}],"name":"D\u00e9partement d'Anesth\u00e9sie R\u00e9animation, AP-HP, H\u00f4pital Beaujon, DMU PARABOL","place":["Clichy, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anais","family":"Codorniu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jyzk483","id-type":"ROR","asserted-by":"publisher"}],"name":"D\u00e9partement d'Anesth\u00e9sie R\u00e9animation, AP-HP, H\u00f4pital Beaujon, DMU PARABOL","place":["Clichy, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Holleville","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jyzk483","id-type":"ROR","asserted-by":"publisher"}],"name":"D\u00e9partement d'Anesth\u00e9sie R\u00e9animation, AP-HP, H\u00f4pital Beaujon, DMU PARABOL","place":["Clichy, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Sigaut","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jyzk483","id-type":"ROR","asserted-by":"publisher"}],"name":"D\u00e9partement d'Anesth\u00e9sie R\u00e9animation, AP-HP, H\u00f4pital Beaujon, DMU PARABOL","place":["Clichy, France"]},{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"NeuroDiderot, Neuroprotection of the Developing Brain, Universit\u00e9 Paris Cit\u00e9, INSERM UMR-S 1141","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Weiss","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jyzk483","id-type":"ROR","asserted-by":"publisher"}],"name":"D\u00e9partement d'Anesth\u00e9sie R\u00e9animation, AP-HP, H\u00f4pital Beaujon, DMU PARABOL","place":["Clichy, France"]},{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre de Recherche sur l'Inflammation, Inserm UMR_S 1149 et Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Jeantrelle","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jyzk483","id-type":"ROR","asserted-by":"publisher"}],"name":"D\u00e9partement d'Anesth\u00e9sie R\u00e9animation, AP-HP, H\u00f4pital Beaujon, DMU PARABOL","place":["Clichy, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_2_2","unstructured":"US FDA. 2017. 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