Rethinking Cefepime Neurotoxicity: An Integrated PK–Neuromonitoring Approach for Neurocritical Care

Abstract Cefepime-induced neurotoxicity (CIN) remains under-recognized despite being a largely exposure-driven and multifactorial complication in neurocritical care. Early identification is often hindered by limited clinical evaluability, delayed electroencephalography (EEG) access, and rapidly evolving renal function that compromises dosing accuracy. Although higher cefepime exposure is consistently associated with increased neurotoxicity risk, no universally accepted therapeutic range clearly separates efficacy from toxicity across critically ill populations. This Viewpoint proposes an anticipatory approach integrating pharmacokinetic principles, therapeutic drug monitoring (TDM), and simplified neuromonitoring to facilitate earlier detection and prevent progression to severe encephalopathy or nonconvulsive seizures. We outline a pragmatic framework to enhance neurological safety while preserving antimicrobial efficacy.