The precise mode of therapeutic action of sulfanilamide on streptococcus can be arrived at only by considering the sum total of factors that inhibit or favor the natural growth of the microorganism under the experimental conditions that obtain, whether in vivo or in vitro. Too sweeping conclusions have hitherto been drawn from the study of a single variable factor, such as an unfavorable temperature or the absence or presence of peptone. We have attempted here to analyze the factors that have hitherto been recognized and some new ones, but particularly the relationship of these factors to one another.

The result obtained on adding sulfanilamide to the streptococcus in the test tube is usually bacteriostasis and not complete destruction of even small numbers of bacteria. This is on the condition that the suspending medium is a favorable one for the growth of the microorganism; the more growth-promoting the medium is the less the bacteriostasis. If, on the other hand, the medium is too poor, or one that in itself inhibits growth, the addition of sulfanilamide may lead to sterilization of the culture.

The conditions for growth of the streptococcus in the body of the rabbit or mouse, depend on the strain of bacteria used, but are on the whole favorable. Defence, however, in the form of phagocytosis by both polymorphonuclear and by mononuclear cells is attempted even in the susceptible animal. When sulfanilamide is used to treat such an animal, or when sulfanilamide-grown (inhibited) streptococci are employed, phagocytosis is pronounced, whether studied in the test tube or in the animal body. In the rabbit the delay by sulfanilamide and resultant increased phagocytosis by polymorphonuclears allows mononuclear cells to accumulate and recovery may result.

Sulfanilamide not only does not completely destroy the streptococcus but does not even impair its innate virulence. It acts upon the streptococcus not only by inhibiting growth but by a temporary inhibition of hemotoxin formation, but only under certain conditions. The drug does not neutralize hemotoxin already formed. No significant effect of sulfanilamide on the formation of leucocidin or fibrinolysin by streptococcus has been evident in our experiments.

Sulfanilamide differs in one important respect from other drugs that are destructive either in the test tube or actually in the body, for protozoa and bacteria. Protozoa fix or adsorb arsenicals and acriflavine that kill them variably in vitro and in vivo. Streptococci fix both gentian violet and acriflavine, which dyes have marked destructive action in the test tube but are less effective in vivo. Sulfanilamide is not diminished at all by contact in vitro with large masses of streptococci, nor does the action of this drug render the microorganism more capable than untreated cocci to adsorb gentian violet or acriflavine, or to be destroyed by these highly bactericidal substances.

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