MK-0991 (formerly L-743,872) is a water soluble semisynthetic echinocandin that possess potent, broad-spectrum antifungal activity. We evaluated the in vitro activity of MK-0991 and an echinocandin derivative LY303366, compared with that of itraconazole, fluconazole, amphotericin B and 5-flucytosine against 400 blood stream isolates of Candida spp. (nine species) obtained from more than 30 different medical centers. MICs for all antifungal drugs were determined by the NCCLS method using RPMI 1640 test medium. Both MK-0991 and LY303366 were very active against all Candida spp. isolates (MIC90, 0.25 and 1 microgram/mL, respectively). MK-0991 was two-fold to 256-fold more active than amphotericin B, fluconazole, itraconazole (except against C. parapsilosis), and 5-flucytosine (except against C. glabrata and C. parapsilosis). LY303366 was comparable to MK-0991, but was fourfold less active against C. tropicalis (MIC90, 0.5 versus 0.12 microgram/mL) and C. parapsilosis (MIC90, > 2 versus 1 microgram/mL). All of the isolates for which fluconazole and itraconazole had elevated MICs (> or = 64 micrograms/mL and > or = 1 microgram/mL, respectively) were inhibited by < or = 0.5 microgram/mL of MK-0991 and LY303366. These results suggest both MK-0991 and LY303366 possess promising antifungal activity and further in vitro and in vivo investigations are warranted.