Kidney Week

Abstract: SA-PO0342

When Treatment Turns Toxic: Cefepime-Induced Acute Tubular Necrosis and Neurotoxicity

Session Information

• AKI: Case Reports - Drug/Toxin Injury, Crystals, Obstruction, and Unusual Presentations
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Mace de Lepinay, Beatrice, NYC Health and Hospitals Elmhurst, Elmhurst, New York, United States

Beatrice Mace de Lepinay, MD

• Stern, Aaron S., NYC Health and Hospitals Elmhurst, Elmhurst, New York, United States

Aaron S. Stern, MD

• Margalioth, Jonathan, NYC Health and Hospitals Elmhurst, Elmhurst, New York, United States

Jonathan Margalioth, MD

• Burgos Guntin, Eusebio Felipe, NYC Health and Hospitals Elmhurst, Elmhurst, New York, United States

Eusebio Felipe Burgos Guntin, MD

Introduction

Cefepime-induced neurotoxicity (CIN) is well recognized, especially in patients with pre-existing renal dysfunction, whereas nephrotoxicity is rare. We describe a case of concurrent neurotoxicity and biopsy-proven acute tubular necrosis (ATN).

Case Description

A 74-year-old man with Pseudomonas aeruginosa osteomyelitis of the foot received intravenous cefepime as part of a planned 6-week outpatient course. In the fifth week of therapy, he presented to the ED with altered mental status and myoclonus. He was normotensive and afebrile. Laboratory studies showed stage 3 oliguric acute kidney injury (creatinine 7.5 mg/dL from a baseline of 0.9 mg/dL; BUN 87 mg/dL). Urinalysis showed 100 mg/dL proteinuria and small blood without RBCs, casts, or pyuria. He was admitted to the ICU, intubated for airway protection, and started on emergent hemodialysis (HD). EEG confirmed nonconvulsive status epilepticus. The serum cefepime level was 23 mg/L, exceeding the toxic threshold (>20 mg/L). Renal biopsy revealed ATN. No other nephrotoxins were identified. After multiple HD sessions, he was extubated and achieved renal and neurologic recovery.

Discussion

Cefepime-induced neurotoxicity (CIN) is reported in up to 15% of ICU patients, most often in those with pre-existing renal dysfunction. The mechanism involves cefepime crossing the blood–brain barrier and exerting concentration-dependent GABA antagonism. Symptoms typically develop within 4 days of initiation. In this case, onset after 5 weeks suggests gradual accumulation due to unrecognized renal decline.

Although cephalosporins are associated with “renal dysfunction” in FDA labeling, cefepime-specific nephrotoxicity is exceedingly rare and has been described primarily as acute interstitial nephritis. In contrast, renal pathology in our case demonstrated tubular epithelial injury with minimal interstitial inflammatory infiltrate, supporting direct tubular toxicity over immune-mediated injury. A proposed mechanism involves β-lactam accumulation in proximal tubular cells via organic anion transporters, leading to mitochondrial dysfunction and oxidative stress. Resultant acute tubular necrosis may further impair cefepime clearance, promoting progressive drug accumulation and worsening neurotoxicity.

This case emphasizes the need for close renal monitoring during prolonged cefepime therapy and consideration of drug level monitoring in high-risk patients.