In vitro antifungal and fungicidal spectra of a new pradimicin derivative, BMS-181184

Abstract

A new pradimicin derivative, BMS-181184, was compared with amphotericin B and fluconazole against 249 strains from 35 fungal species to determine its antifungal spectrum. Antifungal testing was performed by the broth macrodilution reference method recommended by the National Committee for Clinical Laboratory Standards (document M27-P, 1992). BMS-181184 MICs for 97% of the 167 strains of Candida spp., Cryptococcus neoformans, Torulopsis glabrata, and Rhodotorula spp. tested were < or = 8 micrograms/ml, with a majority of MICs being 2 to 8 micrograms/ml. Similarly, for Aspergillus fumigatus and 89% of the 26 dermatophytes tested BMS-181184 MICs were < or = 8 micrograms/ml. BMS-181184 was fungicidal for the yeasts, dermatophytes, and most strains of A. fumigatus, although the reduction in cell counts was less for A. fumigatus than for the yeasts. BMS-181184 was active against Sporothrix schenckii, dematiaceous fungi, and some members of the non-Aspergillus hyaline hyphomycetes. BMS-181184, however, was not fungicidal against members of the family Dematiaceae. BMS-181184 lacked activity or had poorer activity (MICs, > or = 16 micrograms/ml) against Aspergillus niger, Aspergillus flavus, Malassezia furfur, Fusarium spp., Pseudallescheria boydii, Alternaria spp., Curvularia spp., Exserohilum mcginnisii, and the zygomycetes than against yeasts. The activity of BMS-181184 was minimally (twofold or less) affected by changes in testing conditions (pH, inoculum size, temperature, the presence of serum), testing methods (agar versus broth macrodilution), or test media (RPMI 1640, yeast morphology agar, high resolution test medium). Overall, our results indicate that BMS-181184 has a broad antifungal spectrum and that it is fungicidal to yeasts and, to a lesser extent, to filamentous fungi.