TREATMENT OF DISSEMINATED TORULOPSIS-GLABRATA INFECTION WITH DO870 AND AMPHOTERICIN-B

Torulopsis glabrata, an opportunist pathogen in immunosuppressed patie nts, is resistant to many antifungal agents, and there are no establis hed treatment regimens for this organism. The mouse model was used to evaluate treatment with DO870, amphotericin B, fluconazole, and their combination. Mice were immunosuppressed with 5 mg of gold sodium thiom alate given intraperitoneally 1 day prior to intravenous infection wit h 10(8) T. glabrata cells. Treatment with a new antifungal triazole, D O870, at doses ranging from 1 to 50 mg/kg of body weight administered per os either daily or on alternate days; fluconazole at 100 mg/kg twi ce a day per os; or amphotericin B at 3 mg/kg/day intraperitoneally wa s begun 1 day after infection. Treatment for 5 days was followed by sa crifice 2 days later for determining CFU counts in spleen and kidney t issue. For a fluconazole-sensitive isolate (MIC of DO870, < 1.25 mu g/ ml), DO870 at 5 mg/kg/day significantly reduced counts in kidney and s pleen tissue (P < 0.05), amphotericin B was modestly effective, and th e combination of DO870 (25 mg/kg) and amphotericin B (3 mg/kg) was mar kedly more effective than either drug alone (P < 0.01). Three addition al isolates were resistant in vitro to DO870 (MIC, 4 mu g/ml). No redu ction in CFU in kidney or spleen tissue was observed with DO870 when c ompared with counts in control tissue. DO870 is effective in vivo agai nst at least some isolates of T. glabrata and when combined with ampho tericin B can exert additive effects.