In vivo activities of U-100592 and U-100766, novel oxazolidinone antimicrobial agents, against experimental bacterial infections
| Autor: | R. J. Yancey, J K Moerman, Judith C. Hamel, Barbachyn Michael R, Hutchinson Douglas K, Ford Charles W, Steven J. Brickner, D M Wilson, Douglas Stapert |
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| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
Staphylococcus aureus
medicine.drug_class Injections Subcutaneous Antibiotics Administration Oral Microbial Sensitivity Tests medicine.disease_cause Gram-Positive Bacteria Enterococcus faecalis Microbiology chemistry.chemical_compound Mice Staphylococcus epidermidis Vancomycin Acetamides Gram-Negative Bacteria medicine Animals Pharmacology (medical) Oxazoles Oxazolidinones Pharmacology biology Linezolid Bacterial Infections biology.organism_classification Antimicrobial Anti-Bacterial Agents Infectious Diseases chemistry Injections Intravenous Drug Therapy Combination Female Methicillin Resistance medicine.drug Enterococcus faecium Research Article |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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