CP-45,899, a Beta-Lactamase Inhibitor That Extends the Antibacterial Spectrum of Beta-Lactams: Initial Bacteriological Characterization

CP-45, 899 3, 3-dimethyl-7-oxo-4-thia-1-azabicyclo (3. 2. 0) heptane-2-carboxylic acid, 4, 4-dioxide, 2S- (2alpha, 5alpha) is an irreversible inhibitor of several bacterial penicillinases and cephalosporinases. In the presence of low concentrations of CP-45, 899, ampicillin and other beta-lactams readily inhibit the growth of a variety of resistant bacteria that contain beta-lactamases. CP-45, 899 used alone displays only weak antibacterial activity, with the notable exception of its potent effects on susceptible and resistant strains of Neisseria gonorrhoeae. CP-45, 899 appears to be somewhat less potent but markedly more stable (in aqueous solution) than the recently described beta-lactamase inhibitor clavulanic acid. The spectrum extensions provided by the two compounds are similar. A 1: 1 mixture of CP-45, 899 and ampicillin displays marked antimicrobial activity in mice experimentally infected with ampicillin-resistant Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, and Proteus vulgaris.