RESUMO
In a rabbit model of Streptococcus pneumoniae meningitis single doses of 10 and 2.5 mg of the glycopeptide LY333328 per kg of body weight reduced bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as ceftriaxone at 10 mg/kg/h (changes in log CFU, -0.29 +/- 0.21 and -0.26 +/- 0.22 versus -0.34 +/- 0.15/ml/h). A dose of 1 mg/kg was bacteriostatic (change in log CFU, 0.01 +/- 0.11/ml/h). In two animals receiving LY333328 at a dose of 40 mg/kg the bacterial titers were reduced by 0.54 and 0.51 log CFU/ml/h. The penetration of CSF by LY333328 was 1 to 5%. The concentrations of lipoteichoic and teichoic acids in CSF and neuronal damage were similar in ceftriaxone- and LY333328-treated animals.
Assuntos
Antibacterianos/uso terapêutico , Glicopeptídeos , Meningite Pneumocócica/tratamento farmacológico , Streptococcus pneumoniae , Animais , Antibacterianos/farmacocinética , Apoptose , Área Sob a Curva , Líquido Cefalorraquidiano/efeitos dos fármacos , Líquido Cefalorraquidiano/microbiologia , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Lipoglicopeptídeos , Meningite Pneumocócica/metabolismo , Testes de Sensibilidade Microbiana , Neurônios/efeitos dos fármacos , Neurônios/patologia , Penicilinas/farmacologia , Coelhos , Streptococcus pneumoniae/efeitos dos fármacos , Resultado do TratamentoRESUMO
In a rabbit model of Streptococcus pneumoniae meningitis, 5 mg of gemifloxacin mesylate (SB-265805) per kg/h reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as 10 mg of ceftriaxone per kg/h (Deltalog CFU/ml/h +/- standard deviation [SD], -0.25 +/- 0.09 versus -0.38 +/- 0.11; serum and CSF concentrations of gemifloxacin were 2.1 +/- 1.4 mg/liter and 0.59 +/- 0.38 mg/liter, respectively, at 24 h). Coadministration of 1 mg of dexamethasone per kg did not affect gemifloxacin serum and CSF levels (2.7 +/- 1.4 mg/liter and 0.75 +/- 0.34 mg/liter, respectively, at 24 h) or activity (Deltalog CFU/ml/h +/- SD, -0.26 +/- 0.11).