Comparative efficacies of amphotericin B, triazoles, and combination of both as experimental therapy for murine trichosporonosis.
We assessed the activities of amphotericin B deoxycholate, liposomal amphotericin B, fluconazole, and SCH 39304 against 10 strains of Trichosporon beigelii in mice with hematogenous infections. Cyclophosphamide-immunosuppressed CF1 male mice were challenged intravenously with a lethal inoculum of T. beigelii (5 x 10(6) conidia per mouse) and were assigned to different treatment groups or were left untreated. Amphotericin B deoxycholate (1 mg/kg of body weight and liposomal amphotericin B (1, 5, and 10 mg/kg) were given parenterally once daily. Escalating doses (5, 10, and 20 mg/kg/day) of fluconazole and SCH 39304 were tested. We also compared the activity of amphotericin B deoxycholate plus fluconazole (1 and 10 mg/kg/day, respectively) with that of each agent alone. Fluconazole significantly prolonged the survival of mice infected with each of the 10 strains tested. Amphotericin B deoxycholate achieved various responses, improving the outcomes in mice infected with seven of the strains. Liposomal amphotericin B was not more effective than amphotericin B deoxycholate against the two strains tested. Both fluconazole and SCH 39304 reduced the kidney fungal counts in a dose-dependent pattern, with SCH 39304 being more active than fluconazole against one of the two strains tested. The activity of the combination of amphotericin B deoxycholate plus fluconazole appeared to be superior to that of either agent alone, especially in reducing the kidney fungal burden. Fluconazole is more active than amphotericin B deoxycholate against experimental murine trichosporonosis.
Anaissie
E J
EJ
Department of Medical Specialties, University of Texas M. D. Anderson Cancer Center, Houston.
Hachem
R
R
Karyotakis
N C
NC
Gokaslan
A
A
Dignani
M C
MC
Stephens
L C
LC
Tin-U
C K
CK
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005069:Evaluation Studies as Topic; D008081:Liposomes; D008297:Male; D051379:Mice; D009181:Mycoses / Q000188:drug therapy*; D014230:Triazoles / Q000627:therapeutic use*; D014250:Trichosporon
D000935:Antifungal Agents; D004337:Drug Carriers; D008081:Liposomes; D014230:Triazoles; D000666:Amphotericin B