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Convulsive liability of cefepime and meropenem in normal and corneal kindled mice
Akihiro Tanaka1, Kenshi Takechi2, Shinichi Watanabe2
1Division of Pharmacy, Ehime University Hospital, Ehime, Japan akiki@m.ehime-u.ac.jp.
Abstract:
We have reported significantly higher convulsion prevalence in patients treated with cefepime than in those treated with meropenem. Additionally, cefepime-associated convulsions were found only in patients with brain disorders, not renal failure. Here, we compared the convulsive liability of cefepime and meropenem administered intravenously in normal and corneal kindled mice with low seizure thresholds. We used the proconvulsive test in normal mice following pentylenetetrazol (PTZ) injection and electroconvulsive shock at low-stimulus currents and in corneal kindled mice. We also measured electroencephalogram (EEG) activity 1 min after antibiotic injections. Intravenous injection of cefepime and meropenem at 250 or 500 mg/kg of body weight had no effect on PTZ-induced convulsions in normal mice. However, in convulsions induced by electroconvulsive shock at low-stimulus currents, mean seizure stage following cefepime administration at 500 mg/kg was significantly higher than that following saline injection. Additionally, EEG spikes were recorded for mice that were given cefepime (500 mg/kg). In corneal kindled mice following cefepime injection, mean seizure stage was significantly higher than that following meropenem injection. The convulsive liability of cefepime is significantly higher than that of meropenem in normal and corneal kindled mice. In patients with low seizure thresholds, convulsive liability of cefepime may be assumed.
Insights
Cefepime, an antibiotic, is more likely to cause convulsions than meropenem, especially in patients with brain disorders or low seizure thresholds. This study confirms cefepime
Area of Science:
- Neuropharmacology
- Infectious Diseases
- Clinical Neurology
Background:
- Previous reports indicate a higher prevalence of convulsions in patients treated with cefepime compared to meropenem.
- Cefepime-associated convulsions are primarily observed in patients with pre-existing brain disorders, not renal failure.
Purpose of the Study:
- To compare the convulsive liability of cefepime and meropenem.
- To investigate the proconvulsive effects in normal and seizure-prone (corneal kindled) mice models.
Main Methods:
- Utilized pentylenetetrazol (PTZ) and low-stimulus electroconvulsive shock (ECS) to induce convulsions in normal mice.
- Assessed seizure stages and electroencephalogram (EEG) activity following intravenous administration of cefepime and meropenem.
- Evaluated convulsive liability in corneal kindled mice.
Main Results:
- Neither cefepime nor meropenem affected PTZ-induced seizures.
- Cefepime (500 mg/kg) significantly increased seizure stage in ECS-induced convulsions and elicited EEG spikes.
- Cefepime demonstrated significantly higher convulsive liability than meropenem in both normal and corneal kindled mice.
Conclusions:
- Cefepime exhibits a greater potential to induce convulsions compared to meropenem.
- The findings suggest that cefepime's convulsive liability is elevated in individuals with low seizure thresholds or neurological conditions.