RESUMO
The penetration of telavancin was 2% into inflamed meninges and ca. 1 per thousand into noninflamed meninges after two intravenous injections (30 mg/kg of body weight). In experimental meningitis, telavancin was significantly superior to vancomycin combined with ceftriaxone against a penicillin-resistant pneumococcal strain. Against a methicillin-sensitive staphylococcal strain, telavancin was slightly but not significantly superior to vancomycin.
Assuntos
Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Meningites Bacterianas/tratamento farmacológico , Meningite Pneumocócica/tratamento farmacológico , Resistência às Penicilinas , Infecções Estafilocócicas/tratamento farmacológico , Aminoglicosídeos/farmacocinética , Animais , Modelos Animais de Doenças , Lipoglicopeptídeos , Testes de Sensibilidade Microbiana , Coelhos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacosRESUMO
In experimental rabbit meningitis, gemifloxacin penetrated inflamed meninges well (22 to 33%) and produced excellent bactericidal activity (change in log(10) [Deltalog(10)] CFU/ml/h, -0.68 +/- 0.30 [mean and standard deviation]), even superior to that of the standard regimen of ceftriaxone plus vancomycin (-0.49 +/- 0.09 deltalog(10) CFU/ml/h), in the treatment of meningitis due to a penicillin-resistant pneumococcal strain (MIC, 4 mg/liter). Even against a penicillin- and quinolone-resistant strain, gemifloxacin showed good bactericidal activity (-0.48 +/- 0.16 deltalog(10) CFU/ml/h). The excellent antibacterial activity of gemifloxacin was also confirmed by time-kill assays over 8 h in vitro.
Assuntos
Anti-Infecciosos/uso terapêutico , Modelos Animais de Doenças , Farmacorresistência Bacteriana , Fluoroquinolonas , Meningite Pneumocócica/tratamento farmacológico , Naftiridinas/uso terapêutico , Streptococcus pneumoniae/efeitos dos fármacos , 4-Quinolonas , Animais , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Líquido Cefalorraquidiano/metabolismo , Gemifloxacina , Humanos , Testes de Sensibilidade Microbiana , Naftiridinas/farmacocinética , Naftiridinas/farmacologia , Resistência às Penicilinas , Coelhos , Streptococcus pneumoniae/crescimento & desenvolvimento , Resultado do TratamentoRESUMO
In experimental rabbit meningitis, cefepime given at a dose of 100 mg/kg was associated with concentrations in the cerebrospinal fluid of between 5.3 and 10 mg/L and a bactericidal activity of -0.61 +/- 0.24 Delta log(10) cfu/mL x h, similar to the standard regimen of ceftriaxone combined with vancomycin (-0.58 +/- 0.14 Delta log(10) cfu/mL x h) in the treatment of meningitis due to a penicillin- and quinolone-resistant pneumococcal mutant strain (MIC 4 mg/L). Compared with the penicillin-resistant parental strain, the penicillin- and quinolone-resistant mutant was killed more slowly by cefepime and ceftriaxone in time-killing assays in vitro over 8 h.
Assuntos
Anti-Infecciosos , Cefalosporinas/líquido cefalorraquidiano , Meningite Pneumocócica/tratamento farmacológico , Meningite Pneumocócica/microbiologia , Resistência às Penicilinas/genética , 4-Quinolonas , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Cefepima , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/estatística & dados numéricos , Quimioterapia Combinada , Humanos , Meningite Pneumocócica/líquido cefalorraquidiano , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Coelhos , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
BMS 284756 penetrated well into inflamed meninges (44% +/- 11%) and produced good bactericidal activity (-0.82 +/- 0.22 Delta log(10) CFU/ml. h) in the treatment of experimental meningitis in rabbits due to a penicillin-sensitive strain. BMS 284756 monotherapy had a greater potency than the standard regimen of ceftriaxone and vancomycin (-0.49 +/- 0.08 Delta log(10) CFU/ml. h) against a penicillin-resistant strain (MIC, 4 mg/liter). Even against a penicillin- and quinolone-resistant strain, BMS 284756 showed good bactericidal activity (-0.52 +/- 0.12 Delta log(10) CFU/ml. h). The antibacterial activity of BMS 284756 was confirmed by time-killing assays over 8 h in vitro.