Cefepime-Induced Neurotoxicity in the Setting of AKI Requiring Renal Replacement Therapy

ABSTRACT

Introduction: Cefepime is a commonly used parenteral antibiotic for severe infections.85% of the drug is excreted renally and crosses the blood-brain barrier. Cefepime-induced neurotoxicity (CIN) manifests as encephalopathy, myoclonus and seizures. It is reported in patients with renal impairment if administered in high dosage. CIN is reversible after drug discontinuation and faster clinical recovery is achieved by intermittent hemodialysis (IHD). Case Description A 53-year-old female with a history of sleep apnea, obesity, recent COVID pneumonia presented with worsening dyspnea on exertion for 5 days. Physical examination revealed tachycardia, tachypnea, diminished breath sounds at lung bases. Admission laboratory results were a creatinine (Cr), 0.96 mg/dl;BUN, 18 mg/dl. Chest x-ray showed bilateral ground glass pulmonary opacities. Patient was started on Vancomycin 2 g IV every 12 hours and Cefepime 2 g IV every 8 hours. On day 2 she was in septic shock due to E.Coli bacteremia, intubated and started on pressors. Vancomycin was discontinued. On day 8 Cr increased to 1.49 mg/dl. Patient remained on Cefepime without dosage change for six more days despite glomerular filtration rate decreased to 20 ml/min/1.73 m2. On day 18 patient was noted to have altered mental status and jerking movements of upper extremities and head. Cefepime was stopped, Cr peaked at 3.95 mg/dl, BUN was 130 mg/dl at that time. CT scan of head was negative for acute findings. EEG showed focal cortical hyperexcitability, no seizure activity. Cr increased to 4.41 mg/dl, IHD was started. After two IHD sessions jerking movements disappeared, and consciousness improved. Work up for acute kidney injury (AKI) revealed negative Hepatitis B,C, HIV serology. ANA, ANCA serology was negative. Patient regained renal function within 1 week after six IHD sessions. Discussion(s) CIN is a known complication in patients with renal dysfunction but remains challenging to recognize in critically ill patients. Our patient had various causes of altered mental status shock, hypoxemia, uremia. Despite decline in renal function cefepime dose was not adjusted and patient developed CIN which required emergent hemodialysis initiation. A high index of suspicion for CIN is critical when evaluating a patient with AKI. Discontinuation of cefepime and emergent IHD initiation leads to resolution of neurological symptoms within 48 hours.