6-Acetylmethylenepenicillanic acid (Ro 15-1903), a potent beta-lactamase inhibitor. II. Antibacterial properties.
The beta-lactamase inhibitor Ro 15-1903 showed low affinity for penicillin binding proteins (PBPs) of Escherichia coli. When used as a single compound, it displayed no substantial antibacterial activity but in combination with ampicillin, it was similar to clavulanic acid in conferring activity against ampicillin-resistant strains. Some synergy between Ro 15-1903 and piperacillin was found against high inocula of Pseudomonas aeruginosa. Ro 15-1903 markedly enhanced the activity of ceftriaxone against Bacteroides fragilis. In keeping with the in vitro findings, the combination Ro 15-1903 and ampicillin protected mice against systemic infections with beta-lactamase-producing strains of Staphylococcus aureus, Klebsiella pneumoniae and Proteus sp. but not against those with Enterobacter cloacae, Serratia marcescens, and E. coli producing either chromosomally mediated beta-lactamase of type I or plasmid-mediated beta-lactamase of type TEM.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000517:prevention & control; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects; D051379:Mice; D010397:Penicillanic Acid / Q000494:pharmacology* / Q000031:analogs & derivatives; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; C036977:6-acetylmethylenepenicillanic acid; D010397:Penicillanic Acid