Therapy of Neutropenic Rats Infected with Pseudomonas aeruginosa

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Abstract
Rats made profoundly neutropenic with cyclophosphamide were injected with 100 or 1000 LD50 of a strain of P. aeruginosa suspended in mucin. Rats were treated for 24, 48 or 72 h with thrice daily i.m. administration of carbenicillin (400 mg/kg), gentamicin (10 mg/kg), both agents at the same doses or saline. One hour after injection of antibiotics, the mean bactericidal titers in serum were 1:4.7, 1:2.1 and 1:8.6 for rats receiving carbenicillin, gentamicin and a combination of the 2 agents, respectively. Combination chemotherapy produced a greater reduction in mortality rate than did either agent alone for both inoculum sizes and for all 3 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.

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