BMY-28232

BMY-28232, an aminothiazolyl imino methoxy cephalosporin which is available as an orally absorbed acetoxyethyl ester, inhibited strains of methicillin-susceptible Staphylococcus aureus, hemolytic streptococci, Streptococcus pneumoniae, Escherichia coli, Klebsiella species, and many strains of Proteus and Providencia stuartii at concentrations less than 1 microgram/ml, including isolates resistant to cephalexin and cefaclor. It had activity similar to that of cefixime, but was more active against methicillin-susceptible staphylococci. BMY-28232 was a poor substrate for beta-lactamases but was destroyed by the new TEM-3 enzyme, and had less activity against Enterobacter species, Citrobacter freundii, and Proteus vulgaris isolates. Methicillin-resistant staphylococci, Pseudomonas species, enterococci, Listeria monocytogenes, Corynebacterium jeikeium, Bacteroides fragilus and some strains of Clostridium species were resistant to BMY-28232.

BMY-28271, the acetoxyethyl ester of BMY-28232, 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3(Z) -propen-1-yl-3- cephem-4-carboxylic acid, is a new oral cephalosporin. BMY-28232 has a widely expanded spectrum with high activity against gram-positive and gram-negative bacteria. BMY-28232 is far more active than cefixime or cefteram against Staphylococcus aureus and Staphylococcus epidermidis. Against gram-negative bacteria, the activity of BMY-28232 was comparable to or somewhat weaker than that of cefixime or cefteram. BMY-28232 was a poor substrate for various beta-lactamases. Orally administered BMY-28271 had a good therapeutic effect on systemic infections with S. aureus and some gram-negative bacteria in mice. Oral BMY-28271 was efficacious against S. aureus Smith infection: the efficacy of BMY-28271 was 80 to 90 times higher than that of cefixime or cefteram.