From the Guidelines
Cefepime is associated with altered mental status, particularly in patients with renal failure or those who receive high doses.
Association with Altered Mental Status
- The main risk factor for neurological toxicity of beta-lactam antibiotics, including cefepime, is renal failure, which can cause rapid accumulation of the drug 1.
- Cefepime neurotoxicity has been reported in 48% of cases in patients who were overexposed to the drug, and in 26% of cases in patients who were appropriately exposed, taking into account their renal function 1.
- Cefepime trough concentrations above 22 mg/L (with discontinuous infusions) or concentrations at steady state above 35 mg/L (with continuous infusion) have been associated with neurotoxicity in 50% of patients 1.
- The relative pro-convulsive activity of cefepime is 160, compared to penicillin G, which has a relative pro-convulsive activity of 100 1.
Clinical Implications
- Patients experiencing unexplained neurological manifestations, such as acute confusional state, encephalopathy, myoclonus, seizures, or status epilepticus, should be evaluated for possible antibiotic toxicity, and therapeutic drug monitoring (TDM) and temporary suspension of beta-lactam administration should be considered 1.
- The benefit-risk balance of cefepime and other beta-lactam antibiotics may decrease as the plasma free concentration exceeds eight times the minimum inhibitory concentration (MIC) 1.
From the FDA Drug Label
In addition to the events reported during North American clinical trials with cefepime, the following adverse experiences have been reported during worldwide postmarketing experience. Encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and non-convulsive status epilepticus have been reported Although most cases occurred in patients with renal impairment who received doses of cefepime that exceeded the recommended dosage schedules, some cases of neurotoxicity occurred in patients receiving an appropriate dosage adjustment for their degree of renal impairment If neurotoxicity associated with cefepime therapy occurs, consider discontinuing cefepime or making appropriate dosage adjustments in patients with renal impairment.
The association between Cefepime and altered mental status is that encephalopathy (including confusion, hallucinations, stupor, and coma) has been reported in postmarketing experience, particularly in patients with renal impairment who received doses exceeding the recommended schedules, but also in some patients with appropriate dosage adjustments for their renal impairment 2.
From the Research
Association between Cefepime and Altered Mental Status
- Cefepime, a fourth-generation cephalosporin, has been associated with neurotoxic effects, including altered mental status, nonconvulsive status epilepticus (NCSE), and encephalopathy 3, 4, 5, 6, 7.
- These effects can occur in patients with normal renal function, as well as those with impaired renal function 3, 6, 7.
- Risk factors for cefepime-induced neurotoxicity include older age, renal dysfunction, critical illness, and inappropriate dosing based on renal function 5.
- Clinical presentation of cefepime-induced neurotoxicity can be similar to other conditions, such as serotonin syndrome, neuroleptic malignant syndrome, and catatonia, making diagnosis challenging 4.
- Myoclonus has been identified as a characteristic feature of cefepime-induced neurotoxicity, which can help distinguish it from other conditions 4.
- Discontinuation of cefepime and administration of antiepileptics can lead to significant improvement in patients with cefepime-induced neurotoxicity 3, 5, 6.