In vitro antimicrobial activities and spectra of U-100592 and U-100766, two novel fluorinated oxazolidinones

Two new fluorinated oxanolidinones, 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 (MIC(90)s) of U-100592 for some staphylococci and enterococci were slightly lower than those of U-100766 (1 versus 2 mu g/ml). The MIC(90) of U-100592 and U-100766 for oxacillin-resistant Staphylococcus aureus was 2 mu g/ml, the same as observed for oxacillin-susceptible strains. The oxazolidinone MICs for other Staphylococcus spp. were less than or equal to 2 mu g/ml (MIC(50), 0.5 to 1 mu g/ml). All enterococci were inhibited by less than or equal to 4 and less than or equal to 2 mu g of U-100592 and U-100766 per mi, respectively. Against 152 vancomycin-resistant enterococci (five species), both compounds had a narrow range of MICs (0.25 to 2 mu g/ml) and a MIC(90) of 1 mu g/ml. Corynebacterium jeikeium, Bacillus spp., and all tested streptococci were inhibited (less than or equal to 4 mu g/ml). Members of the family Enterobacteriaceae and other gram-negative bacilli were not susceptible (MIC(50), >64 mu g/ml) to either oxazolidinone. Three potencies of U-100592 and U-100766 disks were tested (5, 15, and 30 mu g), and acceptable correlations (r = 0.81 to 0.90) with the measured MICs were observed. Best discrimination of the tentatively susceptible organisms (MICs, less than or equal to 4 mu g/ml) was demonstrated with the 30-mu g 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.