title: In vitro antimicrobial activities and spectra of U-100592 and U-100766, two novel fluorinated oxazolidinones.
abstract: Two new fluorinated oxazolidinones, U-100592 and U-100766, were evaluated against more than 659 gram-positive and -negative organisms and compared with glycopeptides, erythromycin, clindamycin, clinafloxacin, and chloramphenicol. U-100592 and U-100766 were usually equally potent, but the MICs at which 90% of the isolates are inhibited (MIC90s) of U-100592 for some staphylococci and enterococci were slightly lower than those of U-100766 (1 versus 2 micrograms/ml). The MIC90 of U-100592 and U-100766 for oxacillin-resistant Staphylococcus aureus was 2 micrograms/ml, the same as observed for oxacillin-susceptible strains. The oxazolidinone MICs for other Staphylococcus spp. were < or = 2 micrograms/ml (MIC50, 0.5 to 1 microgram/ml). All enterococci were inhibited by < or = 4 and < or = 2 micrograms of U-100592 and U-100766 per ml, respectively. Against 152 vancomycin-resistant enterococci (five species), both compounds had a narrow range of MICs (0.25 to 2 micrograms/ml) and a MIC90 of 1 microgram/ml. Corynebacterium jeikeium, Bacillus spp., and all tested streptococci were inhibited (< or = 4 micrograms/ml). Members of the family Enterobacteriaceae and other gram-negative bacilli were not susceptible (MIC50, > 64 micrograms/ml) to either oxazolidinone. Three potencies of U-100592 and U-100766 disks were tested (5, 15, and 30 micrograms), and acceptable correlations (r = 0.81 to 0.90) with the measured MICs were observed. Best discrimination of the tentatively susceptible organisms (MICs, < or = 4 micrograms/ml) was demonstrated with the 30-micrograms disk concentration. The oxazolidinones demonstrated a dominant bacteristatic action. These oxazolidinones (U-100592 and U-100766) appear promising for treatment of gram-positive organisms that demonstrate resistance to contemporary therapeutic agents.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: D M
authors.initials: DM
authors.lastname: Johnson
authors.forename: M E
authors.initials: ME
authors.lastname: Erwin
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001421:Bacteria, Anaerobic / Q000187:drug effects; D004058:Diffusion; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006095:Gram-Positive Cocci / Q000187:drug effects; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000494:pharmacology*; D023303:Oxazolidinones
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D010080:Oxazoles; D023303:Oxazolidinones; C098011:eperezolid; D000069349:Linezolid