EXPERIMENTAL PSEUDOMONAS-AERUGINOSA SEPSIS - ABSENCE OF SYNERGY BETWEEN TICARCILLIN AND TOBRAMYCIN

Abstract

An in vivo model of P. aeruginosa sepsis was developed with normal and neutropenic guinea pigs injected i.v. with a strain of Pseudomonas demonstrated in vitro to be synergistically susceptible to ticarcillin and tobramycin. Therapy with ticarcillin, tobramycin or a combination of the 2 starting 4 h after i.v. injection of microorganisms was administered every 2 h for periods up to 40 h. Each therapy was associated with significant reductions in bacterial counts in blood, liver, spleen and kidney compared with untreated animals. In no tissue in normal or granulocytopenic animals did therapy with a combination of ticarcillin and tobramycin reduce bacterial counts significantly more effectively than did the better single antibiotic agent alone. Apparently, when ticarcillin and tobramycin are administered to animals at doses equivalent to therapeutic doses given in humans, a synergistic effect in reduction of bacterial counts in parenchymal organs and blood is not observed. These studies may help explain clinical reports in humans describing a lack of synergistic activity of combination antibiotic therapy in patients with Pseudomonas sepsis.