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  • Convulsive liability of cefepime and meropenem in normal and corneal kindled mice.

Convulsive liability of cefepime and meropenem in normal and corneal kindled mice.

Antimicrobial agents and chemotherapy (2014-05-21)
Akihiro Tanaka, Kenshi Takechi, Shinichi Watanabe, Mamoru Tanaka, Katsuya Suemaru, Hiroaki Araki
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tetracaine hydrochloride, ≥99%
Tetracaine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Supelco
Tetracaine hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
Tetracaine for system suitability, European Pharmacopoeia (EP) Reference Standard
USP
Meropenem, United States Pharmacopeia (USP) Reference Standard