title: Epileptogenic activity of methicillin-resistant Staphylococcus aureus (MRSA) antibiotics in rats.
abstract: 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.
authors.affiliation: Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka, Okayama, Japan.
authors.forename: Ashequr
authors.initials: A
authors.lastname: Rahman
authors.forename: Jun
authors.initials: J
authors.lastname: Ago
authors.forename: Naotaka
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kamei
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin; D014640:Vancomycin