The antibacterial activity of ticarcillin/clavulanic acid (BRL28500) against ticarcillin-resistant bacteria

The efficacy of BRL28500, a formulation of ticarcillin (TIPC, 15 parts) and clavulanic acid (CVA, 1 part), against TIPC-resistant strains of Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae was studied both in vitro and in vivo. The MICs of BRL28500 against these beta-lactamase producing strains were lower than those of TIPC or CVA alone against such strains. When BRL28500 was added during the logarithmic growth phase of bacteria at a concentration equivalent to the MIC, it demonstrated marked lytic activity. Cells treated with BRL28500 underwent morphological change, becoming filament-like, similar to those treated with TIPC alone. With CVA alone at concentrations above the MIC the cells assumed a stable round form. In bacterial cultures of the beta-lactamase-producing strains, TIPC was protected from hydrolysis by the presence of CVA. The in vivo activity of BRL28500 against experimental infections in mice caused by beta-lactamase-producing strains of bacteria was superior to that of TIPC alone. TIPC and CVA were found to be well distributed in peritoneal fluid following subcutaneous administration of BRL28500 into mice with peritoneal infections. The residual TIPC concentrations achieved were higher than when TIPC alone was administered. These results suggest that BRL28500 will be effective in the treatment of human infections due to TIPC-resistant bacteria.