Acute Toxicity and Triphasic Waves—The Example of Cefepime

Purpose: Triphasic waves (TWs) have been associated with a host of medication toxicities, and cefepime has emerged recently as a frequently encountered offending agent. This investigation aims to evaluate cefepime-induced encephalopathy and to report the associated clinical, EEG expression with TWs, and the radiologic findings. Methods: A retrospective multicenter observational study examining adult patients with cefepime-induced encephalopathy with generalized periodic discharges on either routine or continuous EEG between January 2014 and January 2020. Clinical, electrographic, and radiologic data were collected. Patients in whom cefepime was not the sole causative factor for their encephalopathy were excluded. Results: Twenty-seven patients with cefepime-induced encephalopathy marked by generalized periodic discharges with triphasic morphology were identified at both centers, whereas no patients were presenting with generalized periodic discharges without TWs. Patients had a median age of 63 years (interquartile range, 56–73). Fifty-six percent of the cohort (15 patients) were <65 years of age. Eighteen patients (67%) had either acute or chronic kidney impairment (either acute kidney injury or chronic kidney disease or both), whereas 81% had preexisting white matter disease on brain imaging. Of these, 14 patients (51%) were classified as either moderate or severe. In the majority of the patients, TWs were either state-dependent or stimulus-sensitive, and in one third of them presented only as stimulus-induced pattern. All patients improved with discontinuation of cefepime. Conclusions: Cefepime toxicity should be considered in the differential diagnosis in encephalopathic patients with TWs. The presence of preexisting white matter disease in these patients should heighten the degree of suspicion, especially in younger patients and patients without renal dysfunction.