What is the likelihood of ceftriaxone (Ceftriaxone)-induced seizure?

Likelihood of Ceftriaxone-Induced Seizures

Ceftriaxone has a low risk of causing seizures, with seizure events primarily occurring in patients with predisposing factors such as renal dysfunction, pre-existing CNS disorders, or excessive dosing. The overall risk is considered low to very low based on available evidence.

Risk Factors for Ceftriaxone-Induced Seizures

The likelihood of ceftriaxone-induced seizures increases significantly in the presence of:

• Renal dysfunction: Impaired clearance leads to drug accumulation 1, 2
• Advanced age: Elderly patients are more susceptible to neurotoxic effects 1
• Pre-existing CNS conditions: Including prior seizures, brain lesions, or encephalopathy 3
• Excessive dosing: Particularly when not adjusted for renal function 1
• Blood-brain barrier disruption: Such as with cerebral trauma or encephalitis 4

Mechanism of Seizure Induction

Ceftriaxone and other cephalosporins can induce seizures through:

• Inhibition of gamma-aminobutyric acid A (GABA-A) receptors, reducing inhibitory neurotransmission 5
• Increasing excitatory neurotransmitter activity 1
• Competitive antagonism at the GABA receptor binding site 5

Clinical Presentation of Ceftriaxone Neurotoxicity

Neurotoxicity may manifest as:

• Altered mental status or encephalopathy (often the first sign)
• Myoclonus or asterixis
• Generalized tonic-clonic seizures
• Nonconvulsive status epilepticus (particularly important to recognize) 2, 5

Monitoring and Prevention

For patients receiving ceftriaxone who are at high risk:

• Adjust dosing based on renal function: This is critical for preventing neurotoxicity 1
• Monitor serum levels in high-risk patients 3
• Consider EEG monitoring: Particularly for patients with unexplained altered consciousness 5
• Be vigilant for nonconvulsive status epilepticus: This can be difficult to diagnose without EEG 5

Management of Ceftriaxone-Induced Seizures

If seizures occur:

1. Immediately discontinue ceftriaxone 2
2. Administer benzodiazepines for acute seizure control
3. Consider hemodialysis in patients with renal failure to enhance drug clearance 5
4. Switch to an alternative antibiotic with lower seizure potential

Comparative Seizure Risk Among Antibiotics

Among β-lactam antibiotics, the relative risk of seizures is:

• Highest: Unsubstituted penicillins and carbapenems (particularly imipenem)
• Moderate: Fourth-generation cephalosporins
• Lower: Third-generation cephalosporins (including ceftriaxone) 3

Important Clinical Considerations

• Ceftriaxone-induced seizures are typically reversible upon drug discontinuation 2
• The evidence for antibiotic-related symptomatic seizures is generally low to very low (Class III-IV) 3
• Nonconvulsive status epilepticus can be easily missed without EEG in patients with unexplained altered mental status 5
• In patients with seizure disorders, consider alternative antibiotics with lower seizure potential when possible 4