Use of discriminative models of Pseudomonas aeruginosa bacteremia in granulocytopenic rats for testing antimicrobial efficacy.

The efficacy of single agent and combination antibiotic therapy was evaluated in rats with severe granulocytopenia and Pseudomonas aeruginosa infection using animal survival, rates of bacteremia and the emergence of resistant organisms as criteria. In this model end points following single agent therapy with imipenem/cilastatin and the synergistic combination of moxalactam plus amikacin were comparable. At a high bacterial challenge dose, equivalent results were obtained using single agent therapy with either piperacillin or ticarcillin. Results were also similar following therapy with piperacillin or ticarcillin in synergistic combination with amikacin. At a lower bacterial challenge dose, aminoglycoside therapy was superior to therapy with the beta-lactams. Therapy with the in vitro synergistic double beta-lactam combination of ceftazidime plus piperacillin was no more effective than therapy with the individual compounds. Results from these studies in this discriminative animal model have in part been used to formulate prospective clinical antibiotic studies in granulocytopenic cancer patients.