Case Presentation: A 94-year-old female with a past medical history of cerebrovascular accident (no residual effects) presented with an intertrochanteric fracture of the right proximal femur after a mechanical fall. On arrival, the patient was afebrile, vital signs hemodynamically stable. On exam, the patient was alert and oriented x3 with no focal deficits, extremities warm and well perfused, with swelling and tenderness of the right hip. Labs significant for baseline serum creatinine (Cr) of 0.8 and positive urinalysis. Patient was started on cefepime 1 gram every 8 hours for a urinary tract infection, and taken to the operating room for femur fracture repair. Postoperatively, the patient was initially alert and oriented x3 and transferred to a general medicine floor. Over the subsequent two days she became disoriented and somnolent. Physical examination revealed occasional rhythmic motions of her tongue. She did not follow commands, opened her eyes only to painful stimuli and was moving all extremities without identifiable focal deficits. Labs showed an elevated blood urea nitrogen (BUN) of 35 and Cr of 2.5. Complete blood count, electrolytes, liver function tests, and ammonia were within normal limits; CT head was negative, no hypercarbia noted, lactate and blood cultures negative. Electroencephalogram (EEG) showed diffuse triphasic waves consistent with marked encephalopathy, no epileptiform activity noted. After aggressive fluid resuscitation, Cr returned to baseline; however, patient remained obtunded. Due to unclear etiology for her deterioration and concern for cefepime toxicity, cefepime was replaced with ceftriaxone. On post-op day 6, within 48 hours of discontinuing cefepime, patient progressively became alert, following commands and interactive with no focal deficits.
Discussion: Cefepime is a fourth-generation cephalosporin commonly used in the inpatient setting. Cefepime is primarily renally excreted, and neurological manifestations have been reported in intensive care unit (ICU) patients with severe renal impairment due to its ability to cross the blood-brain barrier. In this case of severe cefepime neurotoxicity, the patient was at an increased risk due to her age and postoperative acute kidney injury. Symptoms began 48 hours after initiation of cefepime, with disorientation progressing to severe encephalopathy, verging on a comatose state. Additionally, the patient had occasional rhythmic tongue movements, likely myoclonus, along with diffuse triphasic wave on EEG, consistent with patterns documented in other cases of cefepime neurotoxicity. With discontinuation of cefepime, she fully recovered without undergoing additional invasive or costly diagnostic testing.
Conclusions: Cefepime induced neurotoxicity is a preventable and reversible cause of encephalopathy. While previous cases have been reported in the ICU setting, a high index of suspicion for cefepime neurotoxicity should be considered in non-ICU patients with new onset encephalopathy, particularly in the elderly with renal dysfunction. Conversely, cases have been documented despite appropriate renal dose adjustment, along with normal renal function. Concurrent myoclonus and triphasic waves on EEG can further raise suspicion for cefepime neurotoxicity, resulting in cefepime cessation and avoidance of invasive, costly, and unnecessary diagnostic procedures.