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.
Full Text
The Full Text of this article is available as a PDF (235.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brumfitt W., Hamilton-Miller J. M. In-vitro microbiological activities of DuP 105 and DuP 721, novel synthetic oxazolidinones. J Antimicrob Chemother. 1988 Jun;21(6):711–720. doi: 10.1093/jac/21.6.711. [DOI] [PubMed] [Google Scholar]
- Daly J. S., Eliopoulos G. M., Reiszner E., Moellering R. C., Jr Activity and mechanism of action of DuP 105 and DuP 721, new oxazolidinone compounds. J Antimicrob Chemother. 1988 Jun;21(6):721–730. doi: 10.1093/jac/21.6.721. [DOI] [PubMed] [Google Scholar]
- Eustice D. C., Feldman P. A., Zajac I., Slee A. M. Mechanism of action of DuP 721: inhibition of an early event during initiation of protein synthesis. Antimicrob Agents Chemother. 1988 Aug;32(8):1218–1222. doi: 10.1128/aac.32.8.1218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones R. N., Sader H. S., Erwin M. E., Anderson S. C. Emerging multiply resistant enterococci among clinical isolates. I. Prevalence data from 97 medical center surveillance study in the United States. Enterococcus Study Group. Diagn Microbiol Infect Dis. 1995 Feb;21(2):85–93. doi: 10.1016/0732-8893(94)00147-o. [DOI] [PubMed] [Google Scholar]
- Peters J., Kondo K. L., Lee R. K., Lin C. K., Inderlied C. B. In-vitro activity of oxazolidinones against Mycobacterium avium complex. J Antimicrob Chemother. 1995 May;35(5):675–679. doi: 10.1093/jac/35.5.675. [DOI] [PubMed] [Google Scholar]
- Slee A. M., Wuonola M. A., McRipley R. J., Zajac I., Zawada M. J., Bartholomew P. T., Gregory W. A., Forbes M. Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721. Antimicrob Agents Chemother. 1987 Nov;31(11):1791–1797. doi: 10.1128/aac.31.11.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]