Neurotoxicity after intrathecal cefepime administration: case report

Cefepime is a fourth-generation cephalosporin and beta-lactam antibiotic that is generally well tolerated, but there are reports of neurotoxicity proposed to result from competitive antagonism of γ-aminobutyric acid (GABA) receptors. A 10-year-old male with a past medical history of severe traumatic brain injury requiring decompressive craniotomy and cranioplasty with subsequent persistent cerebrospinal fluid (CSF) leak was admitted for scheduled lumbar drain placement and transmastoid repair with ossiculoplasty. Surgery was performed with no complications, and he was admitted to the pediatric intensive care unit (PICU). In the PICU, the patient was inadvertently administered 50.54 mg/kg cefepime intrathecally via the lumbar drain. He immediately developed pruritus of his lower back and gluteal region, emesis, and muscle spasms to his lower extremities and then progressed to status epilepticus. The patient was endotracheally intubated and administered IV lorazepam, midazolam, levetiracetam, propofol, and fosphenytoin. Medical toxicology was consulted and recommended pentobarbital bolus and infusion. Initial cerebrospinal fluid (CSF) and serum cefepime concentrations were 760.6 mg/L and 6.3 mg/L, respectively. CSF exchange was discussed by medical toxicology and neurosurgery but was deemed too high risk by neurosurgery. In lieu of CSF exchange, hemodialysis was recommended by medical toxicology to increase the CSF-plasma cefepime concentration gradient. After two days, serum cefepime concentrations were undetectable, and CSF concentrations had decreased to 89.4 mg/L. After seven days, cefepime was undetectable in CSF. Our case report is the first documented incident of iatrogenic neurotoxicity from the intrathecal administration of cefepime resulting in immediate neurotoxicity with an extremely high CSF cefepime concentration of 760.6 mg/L and serum level of 6.3 mg/L, in contrast to previous reports of toxicity at serum levels as low as 35 mg/L and 22 mg/L and CSF levels of 6-18 mg/L.