What are the considerations for using cefixime in patients with a history of seizures?

Cefixime Use in Patients with Seizure Disorders

Cefixime can be used in patients with a history of seizures as it has a relatively low pro-convulsive potential compared to other beta-lactam antibiotics, but monitoring for neurological symptoms is recommended. 1

Risk Assessment of Beta-Lactam Antibiotics and Seizures

• Beta-lactam antibiotics have varying degrees of pro-convulsive activity, with cefazolin (294) and cefepime (160) having the highest relative pro-convulsive activity compared to penicillin G (100) 1
• Cefixime is not specifically listed in the seizure risk table, but other cephalosporins like ceftriaxone (12) and cefotaxime (8.8) have relatively low pro-convulsive activity 1
• Neurotoxicity of beta-lactam antibiotics has been confirmed in many case series of patients suffering from various neurological disorders including seizures and status epilepticus, sometimes with fatal outcomes 1

Risk Factors for Beta-Lactam Induced Seizures

• The main risk factor associated with neurological toxicity of beta-lactam antibiotics is renal failure, which may cause rapid and significant accumulation 1
• Advanced age (>65 years), acute kidney injury during antibiotic administration, and ICU admission are significant risk factors for cephalosporin-induced neurotoxicity 2
• High plasma concentrations of beta-lactams correlate with increased risk of neurotoxicity 1

Monitoring Recommendations

• Particular attention should be given to possible antibiotic toxicity in patients experiencing unexplained neurological manifestations 1
• Therapeutic drug monitoring (TDM) and temporarily suspension of beta-lactam administration should be considered if neurological symptoms develop 1
• For beta-lactam antibiotics without validated toxicity threshold concentrations, plasma free concentrations should not exceed eight times the MIC (i.e., %fT > 8× MIC) 1

Clinical Management Approach

• Assess baseline renal function before initiating cefixime and adjust dosing accordingly 1
• Monitor for neurological symptoms such as acute confusional state, encephalopathy, myoclonus, seizures, or status epilepticus 1
• Ensure anticonvulsant medications are optimized before initiating cefixime in patients with a history of seizures 3
• If neurological symptoms develop, consider discontinuing cefixime and evaluating for alternative antibiotics with lower seizure risk 1

Alternative Antibiotics for Patients with High Seizure Risk

• Consider antibiotics with lower pro-convulsive activity if appropriate for the infection being treated 1
• Cefotaxime (8.8) and cefoxitin (1.8) have lower relative pro-convulsive activity compared to other beta-lactams 1
• Non-beta-lactam antibiotics may be considered if clinically appropriate for patients with poorly controlled seizures 1

Special Considerations

• Patients with renal impairment require careful monitoring as this is the main risk factor for beta-lactam induced neurotoxicity 1
• A recent study found no statistically significant difference in neurotoxicity between patients with and without a history of seizures when receiving cefepime, suggesting that with proper monitoring and dosing, cephalosporins may be used in patients with seizure history 2
• Recognize that cephalosporin-induced neurotoxicity can occur even with appropriate dosing (26% of cases in one study), highlighting the importance of vigilance regardless of dosing 4