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ABSTRACTThe susceptibilities of 13 clinical isolates of Scedosporium apiospermumand 55 clinical isolates of S. prolificansto new and conventional drugs belonging to three different classes of antifungal agents, the azoles (miconazole, itraconazole, voriconazole, UR-9825, posaconazole), the polyenes (amphotericin B, nystatin and liposomal nystatin), and allylamines (terbinafine), were studied by use of proposed standard M38-P of NCCLS. Low growth-inhibitory antifungal activities were found in vitro for most of the drugs tested against S. prolificansisolates, with the MICs at which 90% of isolates are inhibited (MIC90s) being >8 μg/ml; the MIC90s of voriconazole and UR-9825, however, were 4 μg/ml. S. apiospermumisolates were more susceptible in vitro, with the highest activity exhibited by voriconazole (MIC90s, 0.5 μg/ml), followed by miconazole (MIC90s, 1 μg/ml), UR-9825 and posaconazole (MIC90s, 2 μg/ml), and itraconazole (MIC90s, 4 μg/ml). The MICs of terbinafine, amphotericin B, and the two formulations of nystatin (for which no statistically significant differences in antifungal activities were found for the two species) for S. apiospermumisolates were high. Cross-resistance was observed among all the azoles except posaconazole and among all the polyenes except the lipid formulation. A distribution analysis was performed with the MICs of each drug and for each species. Bimodal and skewed MIC distributions were obtained, and cutoffs indicating the borders of different MIC subpopulations of the distributions were determined on the basis of the normal plot technique. These cutoffs were in many cases reproducible between 48 and 72 h.