{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:31:29Z","timestamp":1792276289380,"version":"4.4.0"},"reference-count":86,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"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":[[2022,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cefepime-induced neurotoxicity (CIN) has been well acknowledged among clinicians, although there are no clear diagnostic criteria or specific laboratory testing to help with its diagnosis. We aimed to summarize the existing evidence regarding CIN and provide future agendas for research.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and Embase for all peer-reviewed articles using keywords including \u2018cefepime\u2019, \u2018neurotoxicity\u2019, \u2018encephalopathy\u2019 and \u2018seizure\u2019, from their inception to 20 January 2022.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We included 92 articles, including 23 observational studies and 69 cases from case reports and case series, in the systematic review. Among 119 patients with CIN, 23.5% were in the ICU at the time of diagnosis and nearly 90% of the cases showed renal dysfunction.<\/jats:p>\n                  <jats:p>Cefepime overdoses were described in 41%. The median latency period of developing CIN from cefepime initiation was 4\u2005days, and about 12% developed CIN during empirical treatment. CIN patients commonly manifested altered mental status (93%), myoclonus (37%) and non-convulsive seizure epilepticus (28%). A serum cefepime trough level of &amp;gt;20\u2005mg\/L would put patients at risk for CIN. CIN-related symptoms were ameliorated in 97.5% by dose reduction or discontinuation of cefepime, with median time to improvement of 3\u2005days. No CIN-associated deaths were reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This systematic review summarizes the current evidence and characteristics of CIN. In the current situation where there are no CIN diagnostic criteria and the drug monitoring platform is not routinely available, candidates for cefepime should be carefully selected. Also, based on these findings, it needs to be appropriately dosed to avoid the development of CIN.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac271","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T07:07:31Z","timestamp":1660633651000},"page":"2908-2921","source":"Crossref","is-referenced-by-count":55,"title":["Cefepime-induced neurotoxicity: systematic review"],"prefix":"10.1093","volume":"77","author":[{"given":"Gozun","family":"Maan","sequence":"first","affiliation":[{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i , Honolulu, HI 96813 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Keitoku","sequence":"additional","affiliation":[{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i , Honolulu, HI 96813 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i , Honolulu, HI 96813 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i , Honolulu, HI 96813 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i , Honolulu, HI 96813 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihun","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i , Honolulu, HI 96813 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideharu","family":"Hagiya","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences , Okayama 700-8558 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0224-7501","authenticated-orcid":false,"given":"Yoshito","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i , Honolulu, HI 96813 , USA"},{"name":"Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences , Okayama 700-8558 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"2022102819180652400_dkac271-B1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1093\/cid\/cir073","article-title":"Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America","volume":"52","author":"Freifeld","year":"2011","journal-title":"Clin Infect Dis"},{"key":"2022102819180652400_dkac271-B2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s10096-005-0021-y","article-title":"Neurotoxicity induced by \u03b2-lactam antibiotics: from bench to bedside","volume":"24","author":"Chow","year":"2005","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2022102819180652400_dkac271-B3","doi-asserted-by":"crossref","first-page":"68S","DOI":"10.1016\/S0002-9343(96)00110-6","article-title":"Safety of cefepime: a new extended-spectrum parenteral cephalosporin","volume":"100","author":"Neu","year":"1996","journal-title":"Am J Med"},{"key":"2022102819180652400_dkac271-B4","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1093\/jac\/dkr138","article-title":"Is cefepime safe for clinical use? 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