6-acetylmethylenepenicillanic-acid and Bacterial-Infections

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.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; beta-Lactamase Inhibitors; Drug Synergism; Escherichia coli; Mice; Penicillanic Acid; Pseudomonas aeruginosa