Clinical, Electroencephalographic Features and Prognostic Factors of Cefepime-Induced Neurotoxicity: A Retrospective Study

Use of Therapeutic Drug Monitoring to Characterize Cefepime-Induced Neurotoxicity

“…The most common EEG abnormalities encountered in patients with cefepime-induced encephalopathy are generalized slowing of the background rhythm, triphasic waves and GPDs. 1,2,17 We used the term sharp waves with triphasic morphology rather than triphasic waves as the use of the latter term is no longer recommended by the ACNS 2012 nomenclature guidelines. 11 Other studies have encountered a higher incidence of NCSE, a difference that is also likely due to the criteria used to classify EEG abnormalities.…”

Cefepime-induced neurotoxicity

“…Preexisting brain injury, old age, high-dose therapy, and increased CNS penetration of cefepime are known risk factors [6,9,10,17,38]. However, CIN has also been reported in patients with normal renal function [5,[18][19][20][21][22]39,40] and in those administered the appropriate dose based on renal function [12][13][14][15][16][17][18][41][42][43]. The cause of CIN in these patients is not known.…”

“…CIN mainly occurs in patients with impaired renal function who have been administered cefepime without dose adjustment, because 85% of cefepime is removed through renal excretion [3][4][5][6][7][8][9][10][11]. However, it has also occurred in patients who have received appropriate doses based on renal function [12][13][14][15][16][17][18] and even in patients with normal renal function [5,[18][19][20][21][22]. Therefore, the U.S. Food and Drug Administration (FDA) issued a safety warning that recommended dose reduction in patients with renal dysfunction, that is, estimated glomerular filtration rate (GFR) < 60 mL/ min [23].…”

“…normalities, some described as CIN with TW or GPD [3,15,17,22,24,43,49,[70][71][72][73][74][75][76], whereas others reported these as CIN with NCSE [4][5][6]13,14,16,18,20,21,42,45,[77][78][79][80][81][82][83][84], depending on the author's view. Some investigators proposed that encephalopathies with GPD or severe metabolic encephalopathies with continuous epileptiform EEG abnormality are not NCSE, and that a coma with continuous generalized epileptiform discharges (coma-GED) should be differentiated from NCSE proper [67,69].…”

Cefepime-Induced Encephalopathy: A Possible Additional Mechanism of Neurotoxicity

“…We read with interest the article "Clinical, electroencephalographic features and prognostic factors of cefepimeinduced neurotoxicity: a retrospective study" by Li et al [1]. Regarding the pathogenesis, as the authors mention, the commonly accepted hypothesis is that cefepime acts as a competitive antagonist of gamma-amino butyric acid (GABA) and subsequently inhibits the inhibitory response, which leads to the over-excitation of electrical activity of neurons and the occurrence of neurological symptoms, including seizure [2].…”