Treatment of streptomycin-susceptible enterococcal experimental endocarditis with combinations of penicillin and low- or high-dose streptomycin

Abstract

We used two strains of streptomycin-susceptible enterococci (MIC, 64 and 128 micrograms of streptomycin per ml, respectively) isolated from patients with infective endocarditis. When combined with penicillin, 20 micrograms of streptomycin per ml killed both strains synergistically in vitro whereas combinations of 5 and 10 micrograms of streptomycin per ml did not act synergistically against either strain. By using the rabbit model of enterococcal experimental endocarditis, animals were treated for 3 days with procaine penicillin (1.2 X 10(6) U intramuscularly three times daily) together with low-dose streptomycin (3.5 mg/kg) or high-dose streptomycin (10 mg/kg) intramuscularly three times daily. The peak concentrations of streptomycin in serum at 0.5 h were 9.2 and 26.8 micrograms/ml in the low- or high-dose group, respectively. When combined with procaine penicillin, both dosages of streptomycin were more effective (P less than 0.01) than procaine penicillin alone for the treatment of enterococcal experimental endocarditis. There was no significant difference in the efficacy of procaine penicillin plus low-dose streptomycin versus procaine penicillin plus high-dose streptomycin therapy of enterococcal experimental endocarditis.