Increase of the Effectiveness of Polyene Antibiotics, with Univalent Cations

Abstract

IN the course of investigations connected with fungistatic antibiotics of polyene character, it was observed that salts of univalent cations increased the effectiveness of these substances to a substantial degree. The experiments were carried out by the agar-diffusion method on potato-extract glucose agar media. The salts were added aseptically in the form of their sterilized aqueous solution to the medium before pouring the test plates. Following a ground layer of 16 ml., a 4-ml. seeded layer containing about 10⁶ spores per ml. was made; the salt concentration was the same in both. The polyene antibiotic was dissolved in methanol and diluted with a 75 per cent (v/v) mixture of methanol and water. By a 3 per cent solution of potassium chloride the effectiveness of nystatin was increased 2-fold against Aspergillus niger, 8-fold against Candida albicans and Kloeckera brevis¹, and 16-fold against Saccharomyces cerevisiae (Fig. 1). This effect can be obtained also with sodium, lithium and ammonium salts, and the anion, either chloride, bromide, iodide, sulphate, citrate, or acetate, makes scarcely any difference. In similar concentrations, calcium and magnesium salts are ineffective. There is a correlation between the concentration of the salt and the increase of the inhibition zone diameter. The increased effectiveness is observed also in liquid media.