Introduction: Cefepime is a fourth-generation cephalosporin with broad-spectrum coverage. Cefepime-induced neurotoxicity is rare, case reports are predominantly in patients with renal insufficiency, for which dosage adjustment is recommended (1-2). However, recent studies have suggested that patients with normal renal function may also develop neurotoxicity, as in our case (3-4). Cefepime-induced neurotoxicity has broad symptomology, including diminished level of consciousness, disorientation, hallucinations, encephalopathy, myoclonus, seizures, and coma. Neurotoxicity is mainly attributed to its ability to cross the blood–brain barrier and manifest concentration-dependent ϒ-aminobutyric acid (GABA) antagonism (5). Cefepime competitively binds to GABA class A receptors, inhibiting endogenous GABA neurotransmission, which leads to central excitation (5). Here, we present a case of cefepimeinduced neurotoxicity in a patient with normal kidney function. We hope this raises awareness of this association and should be maintained in the differential diagnosis of encephalopathy even in patients with preserved renal function.

Case presentation: 80-year-old Caucasian male with medical history of coronary artery disease, atrial fibrillation, dyslipidemia, hypertension, vitamin B12 deficiency, hypothyroidism admitted to inpatient rehab for significant ambulatory dysfunction due to recent diskitis of T11 to L1. Patient had CT guided core biopsy of the disc and cultures grew pseudomonas aeruginosa. Patient was changed from meropenem and vancomycin to cefepime. On day two of cefepime, he became acutely confused with visual and auditory hallucinations, he was alert and oriented to self only without focal neurologic deficit nor other changes to his physical exam. Vital signs were unrevealing. EKG and metabolic workup were also unrevealing including real function, electrolytes, Vitamin B12, folate, TSH and Urinalysis and blood culture. Imaging included computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. Electroencephalography (EEG) showed generalized slowing with no epileptiform discharges. After this workup, cefepime induced neurotoxicity was suspected.

Final Diagnosis and Management: After ruling out common etiologies of encephalopathy, cefepime was discontinued on day six of antibiotic for suspected cefepime induced neurotoxicity.

Outcome: Four days after discontinuation of cefepime, patient’s consciousness improved. He was alert and oriented to place, date and self. Patient recovered without particular sequelae.

References and Resources:

1. Isitan C., Ferree A., and Hohler A.D. (2017). Cefepime induced neurotoxicity: A case series and review of the literature. eNeurologicalSci. V8, 40-43.
2. Schlidt, K., Kadlec, A., Bhandari, S., and Jha, P. (2018). Cefepime-induced Neurotoxicity: Five Cases Reported in a Single Institution. Cureus, 10(11), e3666.
3. Maganti, R., Jolin, D., Rishi, D., and Biswas, A. (2006). Nonconvulsive status epilepticus due to cefepime in a patient with normal renal function. Epilepsy & behavior: E&B, 8(1), 312–314.
4. Meillier, A., and Rahimian, D. (2016). Cefepime-induced encephalopathy with normal renal function. Oxford medical case reports, 2016(6), 118–120.
5. ayne, L. E., Gagnon, D. J., Riker, R. R., Seder, D. B., Glisic, E. K., Morris, J. G., and Fraser, G. L. (2017). Cefepime-induced neurotoxicity: a systematic review. Critical care (London, England), 21(1), 276.
6. American College of Physicians. (19881989). MKSAP: medical knowledge self-assessment program VIII. Philadelphia, PA: American College of Physicians.