Oxazolidinones, a new class of synthetic antibacterial agents in vitro and in vivo activities of DuP 105 and DuP 721..pdf英文资料.pdfVIP

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Nov. 1987, p. 1791-1797 Vol. 31, No. 11 0066-4804/871111791-07$02.00/0 Copyright C 1987, American Society for Microbiology Oxazolidinones, a New Class of Synthetic Antibacterial Agents: In Vitro and In Vivo Activities of DuP 105 and DuP 721 A. M. SLEE,* M. A. WUONOLA, R. J. McRIPLEY, I. ZAJAC, M. J. ZAWADA, P. T. BARTHOLOMEW, W. A. GREGORY, AND M. FORBES Medical Products Department, E. I. du Pont de Nemours Co., Wilmington, Delaware 19898 Received 1 June 1987/Accepted 21 August 1987 DuP 721 (p-acetylphenyloxooxazolidinylmethylacetamide) and DuP 105 (a methylsulfinyl derivative) are orally active representatives of the oxazolidinones, a new class of synthetic antibacterial agents. Their antibacterial spectrum includes staphylococci, streptococci, and Bacteroides fragilis strains. The compounds have equal activity against staphylococcal strains susceptible or resistant to f-lactam antibiotics, including methicillin-resistant strains. The MICs for 90% of the strains (MIC90s) against staphylococcal isolates were 1 to 4 ,ug/ml for DuP 721 and 4 to 16 ,ug/ml for DuP 105, compared with 1 to 2 jig/ml for vancomycin, 0.5 ,ug/ml for ciprofloxacin, and 2 to 16 ,ug/ml for imipenem. The MIC90s against group D streptococci were 4 ,ug/ml for DuP 721, 16 ,ug/ml for DuP 105, and 2 ,ug/ml for vancomycin, ciprofloxacin, and imipenem. MIC90s against B. fragilis isolates were 4 ,ug/ml for DuP 721, 16 ,ug/ml for DuP 105, and 8 ,ug/ml for cefoxitin. DuP 721 and DuP 105 administered by either the oral or the parenteral route were protective against staphylococcal and streptococcal infections in mice. The 50% effective do