IN-VITRO ANTIFUNGAL AND FUNGICIDAL SPECTRA OF A NEW PRADIMICIN DERIVATIVE, BMS-181184

A new pradimicin derivative, EMS-181184, was compared with amphoterici n B and fluconazole against 249 strains from 35 fungal species to dete rmine its antifungal spectrum. Antifungal testing was performed by the broth macrodilution reference method recommended by the National Comm ittee for Clinical Laboratory Standards (document M27-P, 1992). EMS-18 1184 MICs for 97% of the 167 strains of Candida spp., Cryptococcus neo formans, Torulopsis glabrata, and Rhodotorula spp. tested were less th an or equal to 8 mu g/ml, with a majority of MICs being 2 to 8 mu g/ml . Similarly, for Aspergillus fumigatus and 89% of the 26 dermatophytes tested EMS-181184 MICs were less than or equal to 8 mu g/ml EMS-18118 4 was fungicidal for the yeasts, dermatophytes, and most strains of A. fumigatus, although the reduction in cell counts was less for A. fumi gatus than for the yeasts. EMS-181184 was active against Sporothrix sc henckii, dematiaceous fungi, and some members of the non-Aspergillus h yaline hyphomycetes. EMS-181184, however, was not fungicidal against m embers of the family Dematiaceae. BMS-181184 lacked activity or had po orer activity (MICs, greater than or equal to 16 mu g/ml) against Aspe rgillus niger, Aspergillus flavus, Malassezia furfur, Fusarium spp., P seudallescheria boydii, Alternaria spp., Curvularia spp., Exserohilum mcginnisii, and the zygomycetes than against yeasts. The activity of E MS-181184 was minimally (twofold or less) affected by changes in testi ng conditions (pH, inoculum size, temperature, the presence of serum), testing methods (agar versus broth macrodilution), or test media (RPM I 1640, yeast morphology agar, high resolution test medium). Overall, our results indicate that EMS-181184 has a broad antifungal spectrum a nd that it is fungicidal to yeasts and, to a lesser extent, to filamen tous fungi.