Effectiveness of gentamicin and carbenicillin in a rat model against infections with Pseudomonas aeruginosa resistant to gentamicin or gentamicin and carbenicillin

The combination of carbenicillin and gentamicin against gentamicin or gentamicin and carbenicillin resistant Pseudomonas aeruginosa was studied in vitro and in vivo using Andriole's model of intraperitoneal infection of rats. Only those strains for which in vitro marked synergy could be shown were studied in vivo. No significant lowering of mortality in rats was demonstrated using the combination of 1.5 mg/kg/dose of gentamicin and 100 mg/kg/dose of carbenicillin given intrapentoneally or intramuscularly against resistant P. aerginosa. Significant lowering of mortality was demonstrated using the combination or gentamicin alone against sensitive P. aeruginosa as compared to untreated controls. Serum gentamicin levels at 30 min following the low dose (1.5 mg/kg) were lower than the gentamicin MIC in in vitro synergy experiments. A significant lowering of mortality in rats was obtained using the combination of 3 mg/kg/dose of gentamicin and carbenicillin as compared to gentamicin alone for 3 of 5 resistant strains and for 2 of 5 strains when compared to carbenicillin alone. With 4 of 5 strains, significant lowering of mortality was obtained comparing the combination to untreated controls. No significant differences were observed comparing the use of each drug alone to untreated controls for 4 of 5 strains.