Strategies for Safer Cefepime Use to Prevent Neurotoxicity Using the Electronic Health Record

Cefepime, a cornerstone antibiotic in critical care, is associated with underrecognized cefepime-induced neurotoxicity (CIN), particularly in patients 65 years old and older. The true incidence is unknown due to inconsistent monitoring and a lack of diagnostic criteria. The recent Antibiotic Choice on Renal Outcomes (ACORN) trial underscored CIN's clinical significance, finding that cefepime recipients experienced 21% fewer delirium- and coma-free days than those on piperacillin-tazobactam. Current guidelines lack active surveillance recommendations, leading to delayed diagnosis and intervention. We propose three informatics-based strategies to address these challenges: 1) electronic health record (EHR)-integrated datasets utilizing machine learning and natural language processing to identify CIN at scale, 2) automated electroencephalogram tools to provide real-time alerts to clinicians, and 3) dynamic risk scores that continuously update from EHR data to guide prescribing. Implementing these safeguards to optimize CIN prevention, which may be relevant for other antibiotics with neurotoxicity risk, can improve neurologic outcomes and patient safety in critically ill populations.