Cefepime-Induced Neurotoxicity in the Setting of Acute Kidney Injury: A Case Series and Discussion of Preventive Measures

Neurotoxicity is a well-described adverse effect of cefepime. Clinical presentation includes mild neurological deficits, aphasia, impairment of consciousness, and even nonconvulsive status epilepticus. Impaired kidney function is considered the most important risk factor for cefepime-induced neurotoxicity (CIN) and frequently occurs during the course of critical diseases with concomitant acute kidney injury (AKI). Physicians should be aware of situations with increased risk of AKI and the preventive actions required to reduce the risk of CIN. We present three patients with AKI who were treated with cefepime for healthcare-associated infections. Subsequently, two patients developed CIN demonstrating very high cefepime levels in plasma. In the third patient, CIN was likely prevented as the increased risk of neurotoxicity was noted and cefepime treatment was ceased immediately. Diagnosis of CIN might be challenging due to various causes of encephalopathy, in particular in the setting of severely ill patients. Electroencephalogram may assist in establishing the diagnosis, in particular when cefepime therapeutic drug monitoring is not available. As CIN is potentially reversible, it is an important differential diagnosis to consider especially in patients with impaired renal function or being susceptible to AKI. Preventive measures of CIN include therapeutic drug monitoring, consideration of a therapeutic alternative, awareness regarding a potential overestimation of the glomerular filtration rate, and electronic health record alerts about risk constellations for potential overdosing.