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.

In vitro antimicrobial activity of T-91825, a novel anti-MRSA cephalosporin, and in vivo anti-MRSA activity of its prodrug, TAK-599

“…The usefulness of both drugs against MRSA infections, however, is not necessarily satisfied because of their weak bactericidal activities. 3,4 Because vancomycin and linezolid are inactive against gram-negative bacteria, their use does not cover mixed infection with MRSA and gramnegative bacteria. Furthermore, the emergence of MRSA strains with reduced susceptibility to vancomycin and linezolid accelerated an urgent need for new anti-MRSA drugs that are bactericidal against MRSA and active against gram-negative bacteria.…”

Linezolid in the Treatment of Osteomyelitis: Results of Compassionate Use Experience

“…Thus, newer agents are needed for treatment of osteomyelitis due to resistant gram-positive cocci.Two agents now available with activity against these organisms include quinupristin/dalfopristin and linezolid. Linezolid, however, is the only agent approved for treating MRSA infections and has activity against both VREF and VRE faecalis [13,[14][15][16].…”

Simple method for the assay of eperezolid in Brain Heart Infusion broth by high-performance liquid chromatography

“…Eperezolid binds specifically to the 50S ribosomal subunit at the initial phase of protein synthesis and has no effect on the formation of N-formylmethionyl-tRNA, elongation, or termination reactions of translation in bacteria [4,5]. Its significant efficacy has been confirmed in vitro [3,[6][7][8][9] and in animals [10]. Oxazolidinones do not appear to exhibit cross-resistance with other antibiotics [11,12].…”