Enhanced Diallyl Trisulfide has in vitro Synergy with Amphotericin B against Cryptococcus neoformans

Abstract

Although amphotericin B remains the drug of choice for systemic fungal infections, its use is limited by considerable side effects. In The Peoples' Republic of China, commercial Allium sativum derived compounds are widely used as an antifungal drug to treat systemic fungal infections. To evaluate the scientific merit of using A. sativum derived compounds as antifungal agents, we studied a Chinese commercial preparation, allitridium. This preparation contained mainly diallyl trisulfide as confirmed by highperformance liquid chromatography. Allitridium, with and without amphotericin B, was tested to determine its efficacy in killing three isolates of Cryptococcus neoformans. The minimum inhibitory concentration of the commercial preparation was 50 µg/ml and the minimum fungicidal concentration was 100 µg/ml against 1 × 10⁵ organisms of C. neoformans. In addition, the commercial preparation was shown to be synergistic with amphotericin B in the in vitro killing of C. neoformans. This study demonstrates that diallyl trisulfide and other polysulfides possess potent in vitro fungicidal effects and their activity is synergistic with amphotericin B. These observations lend laboratory support for the treatment of cryptococcal infections with both amphotericin B and the Chinese commercial preparation.

Key words

Amphotericin B - garlic - Cryptococcus neoformans - Allium sativum - Alliaceae - allitridium - diallyl trisulfide