Overview of SPA-S-843 in vitro Activity against Filamentous Fungi

Abstract

In this study, we investigated the in vitro antifungal activity of a new water-soluble partricin A derivative, N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diascorbate, coded SPA-843, currently developed by Società Prodotti Antibiotici. The activity of SPA-S-843 was compared to that of amphotericin B against 13 strains of Aspergillus spp., 4 strains of Mucor sp., 4 strains of Rhizopus oryzae, 2 strains Paecilomyces variotii, 5 strains of Penicillium spp., 1 strain of Sporothrix schenkii, 7 strains of Trichophyton spp. and 2 strains of Microsporum spp.; the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) were measured for all the organisms. The in vitro susceptibility testing method employed was an adaptation of the macrodilution reference method for yeasts as described in the National Committee for Clinical Laboratory Standards document M27-A. The in vitro inhibitory activities of SPA-S-843 and amphotericin B against the fungi were evaluated in RPMI-1640 supplemented with L-glutamine and buffered with morpholinepropanesulfonic acid, while the in vitro fungicidal activities were determined by subculturing 0.1 ml from all tubes with no visible growth onto drug-free Sabouraud dextrose agar plates. Comparison with amphotericin B showed that the in vitro inhibitory activity of SPA-S-843 against Aspergillus spp. was better than that of amphotericin B and similar against R. oryzae, P. variotii, Penicillium spp. and S. schenkii. Amphotericin B presented geometric means (GM) of the MICs lower than those of SPA-S-843 against Mucor sp., Microsporum spp. and Trichophyton spp. SPA-S-843 was most fungicidal against Mucor sp. and P. variotii; SPA-S-843 and amphotericin B showed the same fungicidal activity against Aspergillus spp. (GM of the MFCs 12.53 μg/ml), Penicillium spp. (about 12 μg/ml) and S. schenkii (MFC 19.2 μg/ml). Amphotericin B presented GM of the MFC values lower than those of SPA-S-843 against R. oryzae, Microsporum spp. and Trichophyton spp.