Activity of subinhibitory concentrations of dapsone alone and in combination with cell-wall inhibitors againstMycobacterium avium complex organisms

MICs of dapsone (p-p-diaminodiphenylsulfone) were determined radiometrically for ten strains each of theMycobacterium avium complex (MAC) andMycobacterium tuberculosis. MICs ranged from 50 to 250 µg/ml forMycobacterium tuberculosis and from 2 to 100 µg/ml for MAC. However, at a concentration as low as 1.5 µg/ml dapsone significantly inhibited growth of MAC bacteria when used in combination with other drugs specifically acting at the mycobacterial cell-wall level. The latter drugs were used in subinhibitory concentrations, and includedm-fluorophenylalanine (an inhibitor of mycoside-C biosynthesis), ethambutol (an inhibitor of arabinogalactan biosynthesis), and ethionamide (an inhibitor of mycolic acid biosynthesis). Using a radiometric method (Bactec 460-TB), the activity of dapsone was found to be enhanced for 2/10 strains in the presence ofm-fluorophenylalanine, for 3/10 strains in the presence of ethambutol and for 5/10 strains in the presence of ethionamide. A satisfactory correlation between the radiometric data and bacterial viable counts was established.