Spectrum of in vitro antifungal activity of ditiocarb sodium

The immunomodulator ditiocarb sodium (sodium diethyldithiocarbamate, DTC, CAS 148-18-5) is finding increasing use in treating AIDS-patients. Using a macro broth dilution method the minimal inhibitory concentrations and minimal fungicidal concentrations of DTC were studied for 76 fungal strains (54 species) and a broad spectrum of direct antifungal activity was found. All 6 Candida albicans strains tested were inhibited by 1.2 micrograms DTC/ml, a concentration achievable by i.v. administration of DTC in doses as presently used for immunomodulation. All strains of Cryptococcus were inhibited by DTC in concentrations of 2.5 micrograms/ml. In combination with amphotericin B, DTC showed a synergistic mode of action for 6 out of 7 Cryptococcus neoformans strains (checkerboard technique). As far as the direct antifungal activity of DTC was tested (11 strains, 5 species), the combination with amphotericin B or flucytosine showed no antagonistic mode of action. The augmentation of host defences by the immunomodulating agent DTC could become an adjunct to conventional therapy in immunocompromised patients with systemic fungal infections.