What antibiotic has the highest risk of causing seizures?

Seizure Risk Associated with Antibiotics

Among the listed antibiotics, imipenem-cilastatin has the highest risk of causing seizures. 1

Evidence-Based Comparison of Seizure Risk

The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) have published guidelines that directly compare the relative pro-convulsive activity of various antibiotics. According to their data, the seizure risk of the listed antibiotics can be ranked as follows:

Antibiotic	Relative Pro-convulsive Activity
Imipenem	71
Aztreonam	42
Flagyl (metronidazole)	Not listed in the comparative table
Clindamycin	Not listed in the comparative table
Ciprofloxacin	Not listed in the comparative table

Mechanism of Seizure Induction

Imipenem-cilastatin's seizure potential is related to its β-lactam ring structure. The mechanism involves:

• Binding to γ-aminobutyric acid (GABA) receptors, which disrupts inhibitory neurotransmission 2
• Competitive antagonism at GABA receptors, leading to increased neuronal excitability
• Direct effects on the central nervous system, particularly when drug concentrations are elevated

Risk Factors for Imipenem-Associated Seizures

Several factors increase the risk of seizures with imipenem-cilastatin:

• Renal dysfunction (major risk factor due to drug accumulation) 3
• Higher dosages than recommended 3
• Lower body weight 4
• Pre-existing CNS disorders or injury 4
• History of seizures 5
• Advanced age 6
• Pseudomonas aeruginosa infection (independently associated with increased seizure risk) 3

Incidence of Seizures with Imipenem

The reported seizure incidence with imipenem-cilastatin varies:

• 3% overall incidence in phase III studies 3
• 0.9% of seizures were judged to be definitely, probably, or possibly related to imipenem 3
• Higher rates (up to 33%) have been reported in specific populations 2

Clinical Implications and Management

1. Dosage adjustment is critical:

   • Reduce imipenem dose in patients with renal impairment 3
   • Consider body weight when calculating appropriate dosage 5
   • Avoid exceeding 2g/day to minimize seizure risk 5

2. Monitoring recommendations:

   • Monitor renal function regularly during treatment
   • Be vigilant for neurological symptoms in high-risk patients
   • Consider therapeutic drug monitoring in critically ill patients 1

3. Alternative antibiotics:

   • For patients with high seizure risk, consider other carbapenems like meropenem (relative pro-convulsive activity of 16 vs. 71 for imipenem) 1
   • Cefotaxime has one of the lowest seizure potentials among beta-lactams (relative activity 8.8) 1

Comparison with Other Listed Antibiotics

• Aztreonam: Has moderate seizure potential (relative activity 42) but significantly lower than imipenem 1
• Flagyl (metronidazole): Not specifically ranked in the table, but can cause neurotoxicity with prolonged use or high doses
• Clindamycin: Not commonly associated with seizures
• Ciprofloxacin: Fluoroquinolones can cause seizures but are not among the highest-risk antibiotics

In conclusion, when considering seizure potential among the listed antibiotics, imipenem-cilastatin presents the highest risk, particularly in patients with predisposing factors such as renal dysfunction or CNS disorders.