{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:04:34Z","timestamp":1789725874675,"version":"4.0.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH T32 Pediatric Clinical and Developmental Pharmacology Training Program","award":["T32HD069054"],"award-info":[{"award-number":["T32HD069054"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM146701"],"award-info":[{"award-number":["R35GM146701"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Cefepime-induced neurotoxicity (CIN) is a recognized side effect of excessive cefepime exposure and high plasma concentrations in adults. However, the relationship between cefepime concentrations and neurotoxic symptoms in paediatric patients is unknown. The objective of this paper is to explore the relationship between cefepime pharmacokinetics and CIN in a paediatric intensive care unit (PICU) cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>PICU patients with cefepime concentrations measured for a previous PK study were chosen for this cohort. CIN symptoms and related testing were evaluated by retrospective chart review and likelihood of causal association was determined using blinded adjudicators via the Naranjo adverse drug reaction probability scale.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 73 patients with complete data, 43 patients (59%) had either no neurotoxicity or neurotoxicity doubtful to be CIN, while 25 (34%) patients had possible CIN and five (7%) had probable CIN. Symptoms of neurotoxicity included irritability, altered mental status, depressed level of consciousness, myoclonus, seizures and delirium. There were no differences in age, sex, severity of illness or renal dysfunction among groups. Patients with probable CIN had higher cefepime area under the curve (2250 versus 1107\u2005mg*h\/L, P = 0.03) and peak concentrations (232 versus 172\u2005mg\/L, P &amp;lt; 0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This investigation presents a paediatric cohort analysis of CIN and provides preliminary evidence supporting the hypothesis that neurotoxicity risk is probably concentration dependent in this age group and presents with similar spectrum of symptoms as those described in adults.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag075","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:30:59Z","timestamp":1771331459000},"source":"Crossref","is-referenced-by-count":1,"title":["Identification and assessment of paediatric cefepime-induced neurotoxicity in a retrospective cohort of paediatric intensive care patients"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6231-3323","authenticated-orcid":false,"given":"Kathryn","family":"Pavia","sequence":"first","affiliation":[{"name":"Division of Critical Care Medicine, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]},{"name":"Division of Translational and Clinical Pharmacology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E","family":"Day","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H Rhodes","family":"Hambrick","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]},{"name":"Division Nephrology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sibilia","sequence":"additional","affiliation":[{"name":"Division of Critical Care Medicine, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Fenchel","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelli","family":"Paice","sequence":"additional","affiliation":[{"name":"Division of Critical Care Medicine, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]},{"name":"Division of Translational and Clinical Pharmacology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Division of Critical Care Medicine, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7737-8499","authenticated-orcid":false,"given":"Sonya","family":"Tang Girdwood","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH ,","place":["USA"]},{"name":"Division of Hospital Medicine, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"2026030712200792600_dkag075-B1","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: analysis for the global burden of disease study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"2026030712200792600_dkag075-B2","doi-asserted-by":"publisher","first-page":"471","DOI":"10.2165\/00003495-199447030-00007","article-title":"Cefepime. 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