STUDIES ON THE CORRELATION BETWEEN IN VITRO AND IN VIVO ANTIBACTERIAL ACTION OF SULFONAMIDE. II

Investigations in Some Experimental Infections in Mice

Abstract

Several strains of S. pyogenes, E. coli K. pneumoniae, Shigella and Proteus which were determined. for both the degree of virulence to the mouse and sensitivity in vitro to the sulfonamides were used for the present studies. Using these pathogens, therapeutic activities of the sulfonamides were investigated in mice infected by the intraperitoneal route with a variety of challenge doses.
In sensitive strains, it was found that levels of ED₅₀ had changed remarkably by challenge dose of the infected strains and a therapeutic effect of the drug was obtained clearly when below 10⁶ viable cells per mouse had been challenged.
Such results as above mentioned were also observed, to a certain degree, on strains sensitive to the drug in the level of 100-800 mcg/ml, but for high resistant strains, scarcely any therapeutic effects were observed, even when the challenge doses were very small.
When a certain level of challenge dose less than 10⁶ viable cells per mouse was used in all test cultures and the therapeutic effects were compared with each other definite correlation was observed between MIC and ED₅₀ with only a few exceptions. That is to say, degree of the therapeutic effect was dependent mainly on levels of the MIC and challenge dose of the test strain, and then it would seem that there is no remarkable influence of virence of the strain to the effect of the drugs.