Are cephalosporins (a class of beta-lactam antibiotics) associated with seizures?

Cephalosporins and Seizure Risk

Yes, cephalosporins are associated with seizures, particularly in patients with renal impairment, with certain cephalosporins like cefazolin and cefepime carrying significantly higher seizure risk than others. 1

Risk Stratification by Cephalosporin Type

Cephalosporins have varying degrees of pro-convulsive activity, with some posing substantially higher seizure risk than others:

• Highest seizure risk:

  • Cefazolin (294% relative pro-convulsive activity compared to penicillin G)
  • Cefepime (160% relative pro-convulsive activity) 1

• Moderate seizure risk:

  • Imipenem (71%)
  • Ampicillin (21%)
  • Ceftazidime (17%)

• Lower seizure risk:

  • Meropenem (16%)
  • Ceftriaxone (12%)
  • Piperacillin (11%)
  • Cefotaxime (8.8%)
  • Cefoxitin (1.8%) 1

Mechanisms of Neurotoxicity

Cephalosporins primarily cause neurotoxicity through:

• Inhibition of GABA-A receptors, decreasing inhibitory neurotransmission in the brain 2
• Lowering of the seizure threshold 2
• Accumulation in the CNS, particularly when the blood-brain barrier is compromised 2

High-Risk Patient Populations

Patients at increased risk for cephalosporin-induced seizures include:

1. Renal impairment: The most significant risk factor, as reduced clearance leads to drug accumulation 3, 4
2. Elderly patients: Higher susceptibility to neurotoxic effects 4
3. Pre-existing neurological disorders: Including history of seizures or CNS disease 4
4. Blood-brain barrier disruption: From trauma, infection, or inflammation 2
5. Excessive dosing: Particularly without appropriate renal dose adjustment 5

Clinical Manifestations of Neurotoxicity

Cephalosporin neurotoxicity presents as a spectrum of neurological symptoms:

• Encephalopathy/altered mental status
• Myoclonus
• Asterixis
• Seizures (both convulsive and non-convulsive)
• Non-convulsive status epilepticus (NCSE) - particularly difficult to diagnose 3, 4
• Coma in severe cases 4

Monitoring and Prevention

To minimize seizure risk with cephalosporins:

• Dose adjustment: Reduce dose and/or extend dosing interval in patients with renal impairment 5
• EEG monitoring: Consider in high-risk patients or those with unexplained altered mental status 3, 4
• Drug levels: Monitor serum concentrations when available, particularly for cefepime 4
• Vigilance for NCSE: Perform EEG in patients with unexplained altered consciousness during cephalosporin therapy 3, 2

Management of Cephalosporin-Induced Seizures

If seizures occur during cephalosporin therapy:

1. Discontinue the offending drug immediately 6
2. Consider hemodialysis in patients with renal failure to enhance drug clearance 4
3. Administer benzodiazepines or other anticonvulsants for seizure control 4
4. Provide supportive care until drug clearance 7

Concentration-Toxicity Relationship

Specific concentration thresholds associated with neurotoxicity:

• Cefepime: Trough concentrations >22 mg/L (intermittent dosing) or steady-state >35 mg/L (continuous infusion) associated with 50% neurotoxicity risk 1
• Meropenem: Trough >64 mg/L 1
• Piperacillin: >157 mg/L (with tazobactam) predictive of neurological disorders with 97% specificity 1

Important Caveats

• Non-convulsive status epilepticus can be easily missed in critically ill patients but carries significant morbidity and mortality 8
• Cephalosporin-induced neurotoxicity typically develops 2-8 days after treatment initiation 3
• Symptoms may persist despite drug discontinuation until the drug is fully cleared 4
• Avoid exceeding plasma free concentrations above eight times the MIC, as this increases neurotoxicity risk without additional antimicrobial benefit 1