Synergistic activity of carbenicillin and gentamicin in experimental Pseudomonas bacteremia in neutropenic rats

Abstract

Rats made neutropenic with cyclophosphamide were infected intraperitoneally with Pseudomonas aeruginosa. The challenge organism was killed synergistically in vitro by the combination of gentamicin and carbenicillin. Untreated neutropenic rats infected with 3 x 10(6)Pseudomonas died between days 2 and 7, and the overall mortality was 70%. Groups of infected neutropenic rats were treated intramuscularly with 1.5 or 6 mg of gentamicin per kg per dose, 100 or 400 mg of carbenicillin per kg per dose, or 1.5 mg of gentamicin and 100 mg of carbenicillin per kg per dose. Treatment was begun at 2 h postinfection and was continued every 8 h for about 72 h. Cultures of blood and peritoneal washings were performed in control and treated rats at 1, 4, 24, 48, and 72 h postinfection. Gentamicin at either dose level was ineffective in preventing death, but mortality was significantly reduced by high-dose carbenicillin and low-dose combination therapy. In addition, the latter regimens sterilized the peritoneal fluid and blood. Carbenicillin and gentamicin showed in vivo synergy in the treatment of neutropenic Pseudomonas-infected rats.