CP-45,899 in combination with penicillin or ampicillin against penicillin-resistant Staphylococcus, Haemophilus influenzae, and Bacteroides
Retsema, J.A.; English, A.R.; Girard, A.E.
Antimicrobial Agents and ChemoTherapy 17(4): 615-622
ISSN/ISBN: 0066-4804 PMID: 6249192 DOI: 10.1128/aac.17.4.615
CP-45,899 is a new, semisynthetic beta-lactamase inhibitor. When tested alone, CP-45,899 displayed only weak antibacterial activity, with the notable exception of its potent action against penicillin-susceptible and -resistant Neisseria gonorrhoeae. A combination of 3.12 microgram of CP-45,899 per ml with 3.12 microgram of ampicillin per ml, tested in broth cultures, inhibited ca. 90% of resistant Staphylococcus and Haemophilus influenzae strains; similar data were obtained in a variety of media. The same combination of CP-45,899 with ampicillin or penicillin G inhibited 90% of Bacteroides fragilis as interpreted from agar dilution minimal inhibitory concentrations. Inhibitory concentrations of CP-45,899-ampicillin were bactericidal against H. influenzae strains and were as bactericidal as nafcillin or cephalothin against S. aureus. Ampicillin-resistant S. aureus, H. influenzae, and B. fragilis strains did not develop resistance to CP-45,899-ampicillin when transferred as many as six passages in the presence of a sublethal concentration of the combination.