Bactericidal effects of ticarcillin-clavulanic acid against beta-lactamase-producing bacteria in vivo

The comparative efficacies of ticarcillin and ticarcillin plus clavulanic acid have been determined in the mouse against experimental infections caused by ticarcillin-resistant bacteria. The infections studied comprised an intraperitoneal infection, local tissue infections, pyelonephritis, and pneumonia. Both ticarcillin and clavulanic acid penetrated readily to the sites of infection studied and at the doses employed were present at concentrations of the same order as those obtained in humans after the administration of ticarcillin-clavulanic acid formulations (Timentin; Beecham). At these concentrations, the ticarcillin-clavulanic acid combination caused significant bactericidal effects at the sites of infection against the ticarcillin-resistant strains of Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus investigated. The efficacy of ticarcillin plus clavulanic acid against the infections resistant to therapy with ticarcillin demonstrated the beta-lactamase-inhibitory activity of clavulanic acid in vivo.