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Seizure propensity with imipenem
R H Eng1, A N Munsif, B G Yangco
1Medical Service, Veterans Administration Medical Center, East Orange, NJ 07019.
Abstract:
Five patients with seizures related to imipenem administration are described. The potential of imipenem therapy to cause seizure was further studied in a mouse model and compared with the potential for seizure with penicillin and cefotaxime therapy. Penicillin caused ataxia and seizure at a mean mouse serum level of 5800 microns/mL, cefotaxime at 3400 microns/mL, and imipenem at a much lower serum concentration of 1900 microns/mL. The potent activity of imipenem therapy against bacteria, allowing for a clinical dose of only 2 g/d, is unfortunately offset by its higher propensity to induce neurologic symptoms in humans and mice at much smaller doses than would therapy with penicillin G or the cephalosporins, such as cefotaxime.
Insights
Imipenem, a potent antibiotic, can cause seizures in patients and mice at lower doses than penicillin or cefotaxime. This risk of neurologic symptoms offsets its strong antibacterial activity.
Area of Science:
- Pharmacology
- Neuroscience
- Infectious Diseases
Background:
- Imipenem is a broad-spectrum carbapenem antibiotic with potent antibacterial activity.
- Carbapenems, including imipenem, have been associated with central nervous system adverse effects, such as seizures.
- Understanding the dose-dependent neurotoxicity of antibiotics is crucial for patient safety.
Observation:
- Five human patients experienced seizures linked to imipenem administration.
- A comparative mouse model investigated the seizure-inducing potential of imipenem, penicillin, and cefotaxime.
- Imipenem induced seizures at a significantly lower mean serum concentration (1900 mcg/mL) compared to penicillin (5800 mcg/mL) and cefotaxime (3400 mcg/mL).
Findings:
- Imipenem exhibits a higher propensity to induce seizures than penicillin G or cephalosporins like cefotaxime.
- The neurotoxic potential of imipenem is observed in both human patients and a murine model.
- Lower serum concentrations of imipenem are associated with seizure risk.
Implications:
- Clinicians should be aware of the increased risk of seizures with imipenem, especially in patients with predisposing factors.
- The findings suggest a need for careful dosing and monitoring of imipenem therapy to mitigate neurological side effects.
- Further research may explore strategies to reduce imipenem-induced neurotoxicity while preserving its efficacy.