RESUMO
The bactericidal activities of monotherapy with trovafloxacin (-0.37 +/- 0.15 Delta log(10) CFU/ml. h), vancomycin (-0.32 +/- 0.12 Delta log(10) CFU/ml. h), and ceftriaxone (-0.36 +/- 0.19 Delta log(10) CFU/ml. h) for the treatment of experimental meningitis in rabbits due to a clinical penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of ceftriaxone with trovafloxacin considerably improved the killing rates (-0.67 +/- 0.16 Delta log(10) CFU/ml. h) and was slightly superior to ceftriaxone with vancomycin (killing rate, -0.53 +/- 0. 22 Delta log(10) CFU/ml. h), the regimen most commonly used in clinical practice. In vitro, synergy was demonstrated between ceftriaxone and trovafloxacin by the checkerboard method (fractional inhibitory concentration index, 0.5) and by time-killing assays over 8 h.
Assuntos
Anti-Infecciosos/uso terapêutico , Ceftriaxona/uso terapêutico , Fluoroquinolonas , Meningite Pneumocócica/tratamento farmacológico , Naftiridinas/uso terapêutico , Infecções Pneumocócicas/tratamento farmacológico , Animais , Anti-Infecciosos/líquido cefalorraquidiano , Anti-Infecciosos/farmacologia , Ceftriaxona/líquido cefalorraquidiano , Ceftriaxona/farmacologia , Cefalosporinas/líquido cefalorraquidiano , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Meningite Pneumocócica/líquido cefalorraquidiano , Meningite Pneumocócica/microbiologia , Testes de Sensibilidade Microbiana , Naftiridinas/líquido cefalorraquidiano , Naftiridinas/farmacologia , Resistência às Penicilinas , Infecções Pneumocócicas/líquido cefalorraquidiano , Infecções Pneumocócicas/microbiologia , Coelhos , Streptococcus pneumoniae/efeitos dos fármacosRESUMO
The fluoroquinolone trovafloxacin was bactericidal (0.47 +/- 0.23 delta log10 CFU/ml x h after 10 mg/kg of body weight and 0.78 +/- 0.15 delta log10 CFU/ml x h after 30 mg/kg) in the treatment of experimental meningitis caused by a highly penicillin-resistant (MIC and minimum bactericidal concentration = 4 and 4 microg/ml) strain of Streptococcus pneumoniae. Combinations with ampicillin and rifampin were indifferent compared to single drugs.
Assuntos
Anti-Infecciosos/uso terapêutico , Fluoroquinolonas , Meningite Pneumocócica/tratamento farmacológico , Naftiridinas/uso terapêutico , Ampicilina/líquido cefalorraquidiano , Ampicilina/uso terapêutico , Animais , Antibacterianos/líquido cefalorraquidiano , Antibacterianos/uso terapêutico , Anti-Infecciosos/sangue , Anti-Infecciosos/líquido cefalorraquidiano , Ceftriaxona/líquido cefalorraquidiano , Ceftriaxona/uso terapêutico , Testes de Sensibilidade Microbiana , Naftiridinas/sangue , Naftiridinas/líquido cefalorraquidiano , Resistência às Penicilinas , Coelhos , Rifampina/líquido cefalorraquidiano , Rifampina/uso terapêutico , Streptococcus pneumoniae/efeitos dos fármacosRESUMO
CP-99,219 is a new fluoroquinolone that has excellent activity against gram-positive organisms including penicillin- and cephalosporin-resistant Streptococcus pneumoniae strains. In our well-established rabbit model of meningitis, we conducted experiments to determine the concentrations of CP-99,219 in cerebrospinal fluid (CSF) after intravenous administration and its ability to eradicate two penicillin-resistant pneumococcal isolates. The peak and trough concentrations of CP-99,219 in the CSF were from 19 to 25% of the concentrations simultaneously obtained in serum and were unaffected by concomitant dexamethasone administration. Compared with untreated (control) animals, three doses of CP-99,219 given 5 h apart significantly reduced the bacterial count in CSF by 5 to 6 log10 CFU at 10 h. Although 47% of the dexamethasone-treated animals and 18% of those not given the steroid had positive cultures at 24 h (14 h after administration of the last antibiotic dose), the mean bacterial counts did not change from those observed at 10 h. Additionally, only results for animals infected with one of the two pneumococcal strains appeared to be affected by concomitant dexamethasone therapy.