Asunto(s)
Acetamidas/farmacología , Antibacterianos/farmacología , Bacterias Grampositivas/efectos de los fármacos , Oxazoles/farmacología , Oxazolidinonas , Acetamidas/administración & dosificación , Acetamidas/química , Animales , Antibacterianos/administración & dosificación , Antibacterianos/química , Farmacorresistencia Microbiana , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Linezolid , Ratones , Oxazoles/administración & dosificación , Oxazoles/química , Staphylococcus aureus/efectos de los fármacosRESUMEN
The oxazolidinones are a new chemical class of synthetic antibacterial agents that are active orally or intravenously against multidrug-resistant Gram-positive bacteria. Their unique mechanism of action and activity against bacteria that pose therapeutic problems in hospital and community treatments make them promising candidates for antimicrobial agents.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Oxazoles/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infección Hospitalaria/tratamiento farmacológico , Humanos , Oxazolidinonas , Resistencia a las PenicilinasRESUMEN
The Upjohn oxazolidinones, U-100592 and U-100766, are orally bioavailable synthetic antimicrobial agents with spectra of activity against antibiotic-susceptible and -resistant gram-positive pathogens. In several mouse models of methicillin-resistant Staphylococcus aureus infection, U-100592 and U-100766 yielded oral 50% effective doses (ED50) ranging from 1.9 to 8.0 mg/kg of body weight, which compared favorably with vancomycin subcutaneous ED50 values of 1.1 to 4.4 mg/kg. Similarly, both compounds were active versus a Staphylococcus epidermidis experimental systemic infection. U-100592 and U-100766 effectively cured an Enterococcus faecalis systemic infection, with ED50 values of 1.3 and 10.0 mg/kg, and versus a vancomycin-resistant Enterococcus faecium infection in immunocompromised mice, both drugs effected cures at 12.5 and 24.0 mg/kg. Both compounds were exceptionally active in vivo against penicillin- and cephalosporin-resistant Streptococcus pneumoniae, with ED50 values ranging from 1.2 to 11.7 mg/kg in systemic infection models. In soft tissue infection models with S. aureus and E. faecalis, both compounds exhibited acceptable curative activities in the range of 11.0 to 39.0 mg/kg. U-100766 was also very active versus the Bacteroides fragilis soft tissue infection model (ED50 = 46.3 mg/kg). In combination-therapy studies, both U-100592 and U-100766 were indifferent or additive in vivo against a monomicrobic S. aureus infection in combination with other antibiotics active against gram-positive bacteria and combined as readily as vancomycin with gentamicin in the treatment of a polymicrobic S. aureus-Escherichia coli infection. U-100592 and U-100766 are potent oxazolidinones active against antibiotic-susceptible and -resistant gram-positive pathogens in experimental systemic and soft tissue infections.