ON THE MODE OF ACTION OF THE SULFONAMIDES I. ACTION ON ESCHERICHIA COLI

¹ From the Departments of Physiology and Pharmacology, Pediatrics, and Biochemistry, Duke University School of Medicine, Durham, North Carolina

1. Quantitative data on the growth and respiration of E. coli in different media, in the presence and absence of the sulfonamides, has been obtained. Sulfanilamide, sulfapyridine, sulfathiazole and sulfadiazine were employed.

2. The size of inoculum has no real effect on the results. The apparent effect is due to the limitations of the medium and the time course of the inhibition.

3. There is a latent period of sixty to ninety minutes before the action of the sulfonamides on the rate of growth is measurable. Following this, the inhibition develops gradually during the course of three or more hours, depending on the concentration of the drug and the medium.

4. The relationship between rate of growth and drug concentration is plotted. It is simple in a salt-glucose medium, but rather complex in one containing proteose-peptone. These complicated relationships make difficult the evaluation of drug potency and may partly explain the clinical experience that therapeutic result may seem to be independent of sulfonamide blood concentration.

5. They indicate that, as the concentration of the drug is raised, the number of reactions inhibited is increased, and that sulfanilamide cannot inhibit some reaction which is sensitive to the other drugs.

6. At the bacteriostatically active concentrations studied, the sulfonamides do not primarily inhibit the respiration (per cell) of the resting or growing organism.

7. Incubation of non-growing cells with sulfonamide does not affect the subsequent development of inhibition when growth is initiated. Growth was prevented by low temperature, or by withholding ammonia or glucose.

8. A provisional theoretical description of the mode of action of the drug is given.

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