Interactions of itraconazole with amphotericin B in the treatment of murine invasive candidiasis.
The interactions of amphotericin B and itraconazole were studied in murine invasive candidiasis. Candida albicans-infected mice were treated for 10 consecutive days, 24 h after infection. Survival was monitored over 30 days and kidney cultures were done. Mice treated with amphotericin B (0.2 mg/kg/day intraperitoneally) or itraconazole (100 mg/kg/day by oral gavage in two divided doses/ day) had a 30-day survival of 20% or 40%. Concomitant administration of both drugs resulted in 100% mortality; 90% of mice treated with amphotericin B (1 mg/kg/day) survived. With the combination, 100% were dead by day 28 (P < or = .001 vs. amphotericin B). With sequential therapy (i.e., 5 days with one drug and then 5 days with the other), survival was inferior to that with amphotericin B alone but similar to that with itraconazole alone. Kidney culture results confirmed the antagonism of the combination compared with amphotericin B alone. In treatment of murine invasive candidiasis, the concomitant or sequential use of amphotericin B and itraconazole results in a negative interaction.
Sugar
A M
AM
Evans Memorial Department of Clinical Research, Boston Medical Center, Massachusetts 02181, USA. asugar@med-med1.bu.edu
Liu
X P
XP
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D002177:Candidiasis / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D017964:Itraconazole / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008813:Mice, Inbred ICR
D017964:Itraconazole; D000666:Amphotericin B