What are the considerations for using imipenem (a carbapenem antibiotic) in patients with a history of seizure disorders or impaired renal function?

Imipenem and Seizure Risk

Imipenem should be avoided in patients with a history of seizure disorders or CNS lesions, and meropenem is the preferred carbapenem alternative in these populations. 1

Seizure Risk Profile

Imipenem carries a moderate pro-convulsive activity with a relative risk of 71 compared to penicillin G (reference = 100), making it more epileptogenic than meropenem (16) but less than cefepime (160) or cefazolin (294). 1

Key Risk Factors for Imipenem-Associated Seizures

The following factors significantly increase seizure risk and should prompt consideration of alternative antibiotics:

• Pre-existing CNS disorders: Brain lesions, history of seizures, cerebral hemorrhage, or meningitis 2, 3, 4
• Renal impairment: The most critical modifiable risk factor, as imipenem accumulation occurs with decreased clearance 2, 3, 5
• Excessive dosing: Doses exceeding manufacturer recommendations, particularly >2 g/day 3, 5
• CNS infections: Imipenem achieved a 33% seizure rate in one pediatric bacterial meningitis study 1
• Prior CNS chemotherapy: Intrathecal methotrexate administration may predispose to seizures 4

Clinical Recommendations by Patient Population

Patients with Seizure Disorders

Avoid imipenem entirely in patients with known seizure disorders. 2 If a carbapenem is required:

• Use meropenem instead, which has significantly lower pro-convulsive activity (16 vs 71 relative to penicillin G) 1
• Continue baseline anticonvulsant therapy 2
• Monitor neurologically for focal tremors or myoclonus 2

Patients with Renal Impairment

Dose reduction is mandatory for creatinine clearance <90 mL/min. 2

• Do not use imipenem in patients with CrCl <15 mL/min unless hemodialysis is instituted within 48 hours 2
• Adjust dosing based on body weight and renal function to prevent accumulation 3, 5
• When properly dosed for renal function, seizure risk approaches baseline in critically ill patients (4/1,000 patient-days on vs 3.9/1,000 patient-days off imipenem) 5

CNS Infections

Imipenem is contraindicated for meningitis. 2 The FDA label explicitly states:

• "Imipenem and Cilastatin for Injection is not indicated in patients with meningitis because safety and efficacy have not been established" 2
• "Not recommended in pediatric patients with CNS infections because of the risk of seizures" 2
• Use meropenem for bacterial meningitis requiring carbapenem coverage, as it has demonstrated equivalent efficacy to ceftriaxone/cefotaxime with lower seizure risk 1

Critically Ill Patients Without CNS Disease

Imipenem may be used cautiously in critically ill patients without CNS disorders or seizure history, provided:

• Renal function is normal or dose is appropriately adjusted 5, 6
• Total daily dose does not exceed 2 g/day 5
• Dosing is corrected for body mass 5
• Neurologic monitoring is maintained 2

When these precautions are followed, imipenem carries minimal added seizure risk beyond the baseline 16% seizure incidence in critically ill patients 5, 6

Drug Interaction: Valproic Acid

Avoid co-administration of imipenem with valproic acid or divalproex sodium. 2

• Carbapenems reduce valproic acid concentrations below therapeutic range, increasing breakthrough seizure risk 2
• Increasing valproic acid dose is insufficient to overcome this interaction 2
• If imipenem is absolutely necessary in patients on valproic acid, add supplemental anticonvulsant therapy 2

Management of Imipenem-Associated Seizures

If seizures occur during imipenem therapy:

• Discontinue imipenem immediately 2
• Perform neurologic evaluation 2
• Initiate or continue anticonvulsant therapy 2
• Consider levetiracetam for seizure prophylaxis 7
• Switch to alternative antibiotic (meropenem if carbapenem coverage still needed) 1

Preferred Alternative: Meropenem

For infections requiring carbapenem coverage in high-risk patients:

• Meropenem is the preferred carbapenem with 6-fold lower pro-convulsive activity than imipenem 1
• Approved for bacterial meningitis with efficacy equivalent to third-generation cephalosporins 1
• Recommended dosing for critically ill patients: 1 g every 8 hours 1
• Still requires dose adjustment in renal impairment and caution with high plasma concentrations (neurotoxicity threshold: trough >64 mg/L) 1