Epileptogenic activity of methicillin-resistant Staphylococcus aureus (MRSA) antibiotics in rats.
The present study was undertaken to clarify the epileptogenic activity induced by intracerebroventricular injection (i.c.v.) of antibiotics effective in methicillin-resistant Staphylococcus aureus (MRSA) in chronically electrode implanted rats. Teicoplanin (10-100 microg, i.c.v.) caused dose-related electroencephalographic (EEG) seizure characterized by an uninterrupted high voltage and wave complex. At the same time, the rats showed forelimb clonus, head nodding, jumping and severe convulsion. At a high dose (100 microg, i.c.v.), the drug caused a severe twisting immediately after the intracerebroventricular injection (i.c.v.) followed by jumping and violent convulsion with a continuous rhythmic spike and wave complex in EEG. On the other hand, vancomycin (30-1000 microg, i.c.v.) caused no or almost no epileptogenic activity in terms of behavior and in EEG. However, at a high dose (1000 microg, i.c.v.), the drug caused an occasional spike from the hippocampus without showing any behavioral changes in the rats. Fosfomycin (30-1000 microg, i.c.v.), cefazolin (10-100 microg, i.c.v.) and penicillin G (30-300 microg, i.c.v.), used as reference drugs, caused dose-dependent epileptogenic activity in both EEG. From these findings, it was found that teicoplanin caused a potent epileptogenic activity, different to vancomycin. Therefore, it can be concluded that vancomycin may be safety on epileptogenic activity used for the clinical purpose of infections caused by MRSA.
Rahman
Ashequr
A
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka, Okayama, Japan.
Ago
Jun
J
Matsumoto
Naotaka
N
Ishikawa
Takashi
T
Kamei
Chiaki
C
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced*; D008297:Male; D016106:Methicillin Resistance; D051381:Rats; D017208:Rats, Wistar; D013211:Staphylococcus aureus / Q000187:drug effects*; D017334:Teicoplanin / Q000633:toxicity*; D014640:Vancomycin / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D017334:Teicoplanin; D014640:Vancomycin