RESUMO
PURPOSE: To investigate the ocular pharmacokinetics and efficacy of oral trovafloxacin, a novel fluoroquinolone antibiotic, in Staphylococcus epidermidis endophthalmitis. METHODS: Albino rabbits (n = 20) were infected with an intravitreal inoculum of S epidermidis (1.0 x 10(8) colony-forming units [CFU/0.1 ml) and 24 hours later received a single oral dose of trovafloxacin (250 mg/kg). Serum and intraocular samples from infected and control (noninfected) eyes were obtained up to 24 hours after antibiotic administration for measurement of trovafloxacin levels. A second group of rabbits (n = 72) was infected intraocularly and randomized 24 hours later to oral trovafloxacin (250 mg/kg twice a day) for 6 days or no treatment (control). Treatment efficacy was assessed by vitreous culture, clinical examination, and histopathology. RESULTS: Following a single dose of trovafloxacin, maximal vitreous levels were achieved at 8 hours in infected eyes, with a penetration ratio of 36%. Vitreous levels were greater than 15 times the minimum inhibitory concentration of the strain employed. In animals with established endophthalmitis, treated eyes were sterilized after 5 days (P = .0495) compared with control eyes, which autosterilized at 14 days. Clinical and histologic examination revealed significant amelioration of anterior segment inflammation in treated eyes, although severe destruction of posterior segment structures occurred in both groups after 6 days of therapy. CONCLUSIONS: These data support trovafloxacin as a potential oral agent for treatment or prophylaxis of S epidermidis endophthalmitis, although retinal alterations that occur over the period required for vitreous sterilization suggest that it will not replace intravitreal therapy in established endophthalmitis.
Assuntos
Anti-Infecciosos/uso terapêutico , Endoftalmite/tratamento farmacológico , Infecções Oculares Bacterianas/tratamento farmacológico , Fluoroquinolonas , Naftiridinas/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/isolamento & purificação , Administração Oral , Animais , Segmento Anterior do Olho/patologia , Anti-Infecciosos/farmacocinética , Disponibilidade Biológica , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Endoftalmite/metabolismo , Endoftalmite/microbiologia , Endoftalmite/patologia , Infecções Oculares Bacterianas/metabolismo , Infecções Oculares Bacterianas/patologia , Masculino , Testes de Sensibilidade Microbiana , Naftiridinas/farmacocinética , Coelhos , Distribuição Aleatória , Retina/patologia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/patologia , Corpo Vítreo/metabolismo , Corpo Vítreo/microbiologiaAssuntos
Antibacterianos/uso terapêutico , Nocardiose/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Sistema Nervoso Central/microbiologia , Modelos Animais de Doenças , Humanos , Pulmão/microbiologia , Camundongos , Testes de Sensibilidade Microbiana , Nocardiose/etiologia , Nocardiose/patologia , Pele/microbiologiaRESUMO
A clinical isolate of Escherichia coli HM73 (MIC norfloxacin 2 mg/L) was isolated during norfloxacin therapy from an urinary tract infection in a patient who had been previously treated with pipemidic acid and infected by E. coli HM72 (norfloxacin 0.25), known to harbour a substitution Ser 83-->Leu in the gyrA gene. No difference in accumulation of norfloxacin was found between the two strains. DNA gyrases were isolated by affinity chromatography and assayed for supercoiling activity in the presence of norfloxacin. The minimal effective doses (MEDs) were 20 mg/L, for HM72 and 80 for HM73. DNA sequencing identified in HM73, two mutations leading to substitutions Ser 83 to Leu and Asp 87 to Gly.