Comparison of ciprofloxacin with azlocillin plus tobramycin in the therapy of experimental Pseudomonas aeruginosa endocarditis

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Abstract
The efficacy of ciprofloxacin (Bay o 9867), a promising new quinolone, was compared with the efficacy of azlocillin plus tobramycin in rabbits with experimentally induced Pseudomonas aeruginosa endocarditis. The MBCs of ciprofloxacin, azlocillin, and tobramycin against the test strain were 0.5, 8, and 4 micrograms/ml respectively. Ciprofloxacin at a concentration of 50 mg/kg or azlocillin at a concentration of 200 mg/kg in combination with tobramycin at a concentration of 5 mg/kg was administered intramuscularly at 8-h intervals for 4 days. Both regimens produced median peak serum bactericidal titers of 1:8. The concentrations of ciprofloxacin, azlocillin, and tobramycin in serum, 1.8 +/- 0.7, 154 +/- 48, and 9.1 +/- 2.4 micrograms/ml (mean +/- standard deviation), respectively, closely approximated concentrations found in humans after accepted dosages. At the end of treatment, the titers of P. aeruginosa were 3.0 +/- 1.6 log10 CFU/g of vegetation (mean +/- standard deviation) for recipients of ciprofloxacin and 3.2 +/- 1.3 log10 CFU/g of vegetation for recipients of azlocillin plus tobramycin. These values compared with control titers of 7.3 +/- 1.6 CFU/g. These data indicate that at the doses used, ciprofloxacin was as effective as azlocillin plus tobramycin in the treatment of P. aeruginosa endocarditis in rabbits. Since the latter drug combination has proven efficacy, ciprofloxacin deserves further evaluation in the therapy of systemic infections in animal models and in humans.