Sulfonamide Activity as Influenced by Variation in pH of Culture Media *

In view of recent reports suggesting a possible relationship between ionization and the bacteriostatic action of the sulfonamides, it was thought that it might be of interest to study the activity of several sulfonamide derivatives as well as that of p-aminobenzoic acid under a widely varying pH range of the culture medium. Therefore, experiments were carried out with a strain of Staph. aureus which grew in a synthetic medium at pH values between 6.5 and 8.9. Tests for bacteriostasis by the sulfonamides and for the reversal of sulfonamide activity by p-aminobenzoic acid were made at several pH levels. The sulfonamide compounds used were sulfanilamide, sulfaguanidine, sulfapyridine, sulfathiazole, and sulfadiazine. The medium employed was that described by Gladstone3 for the cultivation of Staph. aureus. It consisted of a mixture of amino acids, salts, and glucose to which were added the growth factors, nicotinic acid and thiamin chloride. This medium was sterilized by filtration through a Mandler filter candle and the pH was adjusted aseptically after sterilization. A glass electrode potentiometer was used in making pH adjustments and determinations in all experiments. The test strain of Staph. aureus was cultivated exclusively in the chemically defined medium throughout the course of the investigation. Sulfonamide stock solutions were made up on a molar basis in the test medium and the pH was adjusted by adding small amounts of concentrated solutions of HCI or NaOH. The various concentrations of the sulfonamide compounds to be tested were obtained by making serial dilutions of the stock solutions, so that each tube in a test contained half the sulfonamide -concentration of the one