Comparative inhibition beta-lactamases by novel beta-lactam compounds.
The beta-lactamase-inhibiting activity of CP-45,899, 3,3-dimethyl-7-oxo-4-thia-1-azabicylo(3,2,0)heptane-2-carboxylic acid, 4,4-dioxide [2S-(2alpha,5alpha)], was investigated and compared with the beta-lactamase-inhibiting activity of clavulanic acid and dicloxacillin. CP-45,899 was an effective inhibitor of Staphylococcus aureus beta-lactamase and of those beta-lactamases of gram-negative bacteria which are primarily active against penicillins or equally active against penicillins and cephalosporins. The reaction of CP-45,899 with beta-lactamases was a concentration- and time-dependent event. CP-45,899 acted as a competitive inhibitor of plasmid-mediated S. aureus, Escherichia coli, and Shigella sonnei beta-lactamases and inducible Klebsiella beta-lactamase. CP-45,899 was a poor inhibitor of inducible or constitutive chromosomally mediated beta-lactamases of indole-positive Proteus, Citrobacter, and Enterobacter. CP-45,899 had lower kinetic constants for inhibition of hydrolysis than did clavulanic acid against many of the beta-lactamases which both inhibited.
D000667:Ampicillin / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000201:enzymology; D004009:Dicloxacillin / Q000494:pharmacology; D006868:Hydrolysis; D007700:Kinetics; D013844:Thiazoles / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D013844:Thiazoles; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D000667:Ampicillin; D004009:Dicloxacillin