STUDIES ON PIROMIDIC ACID (REPORT II)

With Special Reference to Sensitivity Disc Test and its Clinical Application

Abstract

1) Piromidic acid has been appreciated to be applicable to the urinary tract infections as well as the biliary tract infections. In the treatment of these diseases, it is considered that the concentration of active substances in the infected tissues, i.e. active levels in blood and in urine in the case of urinary tract infection and the ones in blood and in bile in the case of biliary tract infection, play important roles. According to our experiments, active principles of piromidic acid in body fluids were unchanged piromidic acid and β-hydroxypiromidic acid, a main active metabolite and the average ratios of them were about 4 : 1 in blood, about 1 : 10 in urine and about 3 : 1 in bile, respectively. It was considered under these circumstances that the mixture of piromidic acid and β-hydroxypiromidic acid might be one representative at the ratio of 1 : 1-4 if only one ratio should be selected for simplification of clinical tests on piromidic acid.
2) In vitroantibacterial activity of the mixture of piromidic acid and 8-hydroxypiromidic acid was almost similar at the ratios of 1 : 1, 1 : 3 and 1 : 4.
3) On the basis of these results, sensitivity discs containing piromidic acid and β-hydroxypiromidic acid at the ratio of 1 : 1, were prepared. Correlations between minimum inhibitory concentrations by the serial dilution method and diameters of inhibition zones by the disc method were repeatedly investigated using 112 strains of 18 bacterial species. Then the linear regression curves were drawn for the following disc methods ; 1) conventional method where incubation time was about 16 hours, 2) delayed method where incubation time was about 24 hours, 3) rapid method where incubation time was 3-4 hours with heavy inoculum and 4) rapid method where incubation time was 5-6 hours with heavy inoculum, respectively.
4) Piromidic acid was administered in 4 cases of urinary tract infection and was effective in all cases. Infecting bacteria isolated from these cases were all determined to be sensitive by means of the disc method above mentioned. The results indicated the usefulness of the sensitivity test using the disc containing piromidic acid and β-hydroxypiromidic acid simultaneously for the laboratory control of chemotherapy with piromidic acid.