Therapy of neutropenic rats infected with Pseudomonas aeruginosa

Rats made profoundly neutropenic with cyclophosphamide were injected with 100 or 1,000 50% lethal doses of a strain of Pseudomonas aeruginosa suspended in mucin. Rats were treated for 24, 48, or 72 hr with thrice daily intramuscular administration of carbenicillin (400 mg/kg), gentamicin (10 mg/kg), both of these agents at the same doses, or saline. One hour after injection of antibiotics, the mean bactericidal titers in serum were 1:4.7, 1:21., and 1:8.6 for rats receiving carbenicillin, gentamicin, and a combination of the two agents, respectively. Combination chemotherapy produced a greater reduction in mortality rate than did either agent alone for both inoculum sizes and for all three durations of therapy. Gentamicin was at least as effective as carbenicillin regardless of inoculum size or duration of therapy. Fourfold or greater increases in minimal inhibitory concentrations of P. aeruginosa were seen in 54% of postmortem blood culture isolates from animals treated with carbenicillin, in 15% from rats treated with gentamicin, and in none from animals receiving both agents.