Joint Action of Penicillin with Chloramphenicol on an Experimental Streptococcal Infection of Mice. ∗

Abstract

In the course of studies on the effects of antibiotics on enterococci it was observed that chloramphenicol interfered with the early bactericidal action of penicillin (1). In the presence of both penicillin and chloramphenicol the rate of bactericidal action was considerably slower than with penicillin alone. It was of interest to determine whether this apparent antagonism between two antibiotic agents is limited to an in vitro phenomenon or whether it could be demonstrated in vivo. Since enterococci are essentially nonpathogenic for small laboratory animals, a highly fatal infection with beta hemolytic streptococci was used in the present experiments.

Materials and methods. White Swiss mice weighing about 20 g, from a heterozygous stock, were used in all experiments. The infections were produced with a beta hemolytic, group A, type 3, streptococcus, strain C 203, kindly supplied by Dr. H. Eagle. The virulence of this organism was kept at high level by passage through mice once or twice weekly. Cultures were grown in 5% sheep blood broth at 37°C for 18 hours. The LD₅₀ for intraperitoneal injection of mice consisted of 60-100 organisms contained in 0.2 ml of a 10^-6 dilution of an 18 hour culture. In all experiments 0.2 ml of a 10^-4 dilution of culture, about 100 LD₅₀, was injected intraperitoneally as the infecting dose. Commercial crystalline sodium penicillin G was freshly dissolved in saline prior to each experiment and suitably diluted. Chloramphenicol (Chloromycetin lot No. 1294161†) was dissolved in saline in a concentration of 4 mg/ml and sterilized by Seitz nitration. Such stock solutions were kept at 4°C for 2-3 weeks without apparent deterioration. Final dilutions were prepared in saline just prior to each experiment. Mice were treated one hour after infection.