To investigate the most common electroencephalographic (EEG) abnormalities reported in cefepime-associated neurotoxicity (CAN) and reassess their classification using the ACNS 2021 Critical Care EEG (CCEEG) terminology.

Although CAN is well-recognized in critical care practice, accurate characterization of its EEG abnormalities remains elusive. Since the release of the ACNS 2021 CCEEG nomenclature, no review has yet applied these terminologies to reanalyze case-level evidence within a validated framework. Reclassification is essential to refine diagnostic heuristics and improve clinical decision-making in CAN.

A systematic literature search across multiple databases identified studies from 1990 to 2025. Inclusion criteria were case reports, case series and retrospective studies with individual EEG data on CAN. Exclusions included animal studies, systematic reviews, retrospective reviews with aggregate results, studies without EEG data and non-English publications.

Among 83 patients, the most frequent EEG abnormalities were background slowing in 67 (81%), generalized sharp waves in 52 (63%), sharp waves with triphasic morphology in 44 (53%) and generalized periodic discharges in 38 (46%). Nonconvulsive status epilepticus (NCSE) was reported in 37 (45%) but only 10 met electrographic/electroclinical criteria per ACNS 2021 CCEEG nomenclature. Focal seizures, generalized seizures, and focal status epilepticus were less common, occurring in 8 (10%), 6 (7%), and 3 (4%) respectively. Other findings included generalized convulsive status epilepticus in 3 (4%), generalized rhythmic delta activity in 4 (5%), lateralized rhythmic delta activity in 1(1%), lateralized periodic discharges in 2(2%), multifocal sharp waves in 2(2%), discontinuous background in 1(1%) and background suppression in 1(1%).

Although NCSE has been frequently reported in CAN, reclassification using the ACNS 2021 CCEEG terminology shows that, based on our data, only a minority of cases fulfil the formal electrographic/electroclinical criteria. Applying standardized EEG terminology is essential to distinguish ictal from interictal findings, prevent unwarranted anti-seizure medication escalation and enhance antimicrobial stewardship in critical care.