Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721.
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 beta-lactam antibiotics, including methicillin-resistant strains. The MICs for 90% of the strains (MIC90s) against staphylococcal isolates were 1 to 4 micrograms/ml for DuP 721 and 4 to 16 micrograms/ml for DuP 105, compared with 1 to 2 micrograms/ml for vancomycin, 0.5 microgram/ml for ciprofloxacin, and 2 to greater than 16 micrograms/ml for imipenem. The MIC90s against group D streptococci were 4 micrograms/ml for DuP 721, 16 micrograms/ml for DuP 105, and 2 micrograms/ml for vancomycin, ciprofloxacin, and imipenem. MIC90s against B. fragilis isolates were 4 micrograms/ml for DuP 721, 16 micrograms/ml for DuP 105, and 8 micrograms/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 doses were 2 to 10 mg/kg for DuP 721, 9 to 23 mg/kg for DuP 105, and 2 to 12 mg/kg for vancomycin. These results indicate that further studies of compounds of the oxazolidinone series are warranted.
Slee
A M
AM
Medical Products Department, E. I. du Pont de Nemours & Co., Wilmington, Delaware 19898.
Wuonola
M A
MA
McRipley
R J
RJ
Zajac
I
I
Zawada
M J
MJ
Bartholomew
P T
PT
Gregory
W A
WA
Forbes
M
M
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy; D005260:Female; D051379:Mice; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D023303:Oxazolidinones
D000890:Anti-Infective Agents; D010080:Oxazoles; D023303:Oxazolidinones; C054755:4-acetylphenyloxooxazolidinylmethylacetamide; C054753:4-methylsulfinylphenyloxooxazolidinylmethylacetamide