Activities of D0870, a novel triazole, against Candida lusitaniae and Trichosporon beigelii in experimental murine infections.
Candida lusitaniae and Trichosporon beigelii may cause life-threatening infections in the immunocompromised host and may be resistant to amphotericin B. We assessed the activities of a new triazole, D0870, against one T. beigelii and four C. lusitaniae strains, in comparison with those of fluconazole and amphotericin B. Immunosuppressed CF1 mice, intravenously infected with each fungal strain, received 3 days of therapy with oral D0870 (5 or 25 mg/kg of body weight daily), fluconazole (5 to 50 mg/kg daily), or parenteral amphotericin B (1 or 2 mg/kg daily). Survival was significantly prolonged and kidney fungus titers were reduced in mice treated with D0870 compared with untreated mice (P < or = 0.05). Treatment with D0870 was significantly more effective than that with amphotericin B or fluconazole in animals infected with two of the C. lusitaniae strains and equally effective for the remaining two C. lusitaniae strains and the T. beigelii strain. Fluconazole and amphotericin B failed to improve the survival of mice infected with one and two C. lusitaniae strains, respectively. D0870 was active against all the organisms tested, including those resistant to fluconazole and amphotericin B.
Karyotakis
N C
NC
Department of Medical Specialties, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Dignani
M C
MC
Hachem
R
R
Anaissie
E J
EJ
D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy*; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014250:Trichosporon / Q000187:drug effects*
D000935:Antifungal Agents; D014230:Triazoles; C058219:ICI 195739