Convulsive liability of cefepime and meropenem in normal and corneal kindled mice.
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.
Division of Pharmacy, Ehime University Hospital, Ehime, Japan akiki@m.ehime-u.ac.jp.
Akihiro
A
Tanaka
Division of Pharmacy, Ehime University Hospital, Ehime, Japan.
Kenshi
K
Takechi
Division of Pharmacy, Ehime University Hospital, Ehime, Japan.
Shinichi
S
Watanabe
Division of Pharmacy, Ehime University Hospital, Ehime, Japan.
Mamoru
M
Tanaka
School of Pharmacy, Shujitsu University, Okayama, Japan.
Katsuya
K
Suemaru
Division of Pharmacy, Ehime University Hospital, Ehime, Japan.
Hiroaki
H
Araki
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000077723:Cefepime; D002511:Cephalosporins / Q000009:adverse effects*; D003292:Convulsants / Q000008:administration & dosage; D004198:Disease Susceptibility; D004334:Drug Administration Schedule; D004569:Electroencephalography; D004597:Electroshock; D007275:Injections, Intravenous; D008297:Male; D000077731:Meropenem; D051379:Mice; D008813:Mice, Inbred ICR; D010433:Pentylenetetrazole / Q000008:administration & dosage; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D012720:Severity of Illness Index; D013045:Species Specificity; D013845:Thienamycins / Q000009:adverse effects*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D003292:Convulsants; D013845:Thienamycins; D000077723:Cefepime; D000077731:Meropenem; D010433:Pentylenetetrazole