Comparison of the efficacies of amphotericin B, fluconazole, and itraconazole against a systemic Candida albicans infection in normal and neutropenic mice.
We compared the efficacies of the new triazole antifungal drugs fluconazole and itraconazole with that of amphotericin B in vitro and in an animal model of systemic candidiasis in normal and neutropenic mice. Antifungal treatment with fluconazole (2.5 to 20 mg/kg orally twice daily), itraconazole (10 to 40 mg/kg orally twice daily), or amphotericin B (0.1 to 4 mg/kg intraperitoneally once daily) was started 1 day after intravenous injection of 10(4) Candida albicans into normal mice or 10(3) C. albicans into neutropenic mice; the drugs were administered for 2 days. In normal mice the efficacy of treatment, which was assessed on the basis of the number of C. albicans cultured from the kidney, was greater for amphotericin B than for the triazoles. Fluconazole was more potent than itraconazole on the basis of equivalent doses, although itraconazole was more potent on the basis of the amount of free drug that was available. In neutropenic mice amphotericin B was less effective than it was in normal mice, whereas the triazoles were equally effective in normal and neutropenic mice. This was not expected, since in vitro data showed that amphotericin B was highly fungicidal, whereas both fluconazole and itraconazole had only a minimal effect on the growth of C. albicans in vitro.
Van t Wout
J W
JW
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Mattie
H
H
van Furth
R
R
D000380:Agranulocytosis / Q000150:complications*; D000666:Amphotericin B / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D015725:Fluconazole; D006207:Half-Life; D017964:Itraconazole; D007654:Ketoconazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009503:Neutropenia / Q000150:complications*; D014230:Triazoles / Q000493:pharmacokinetics / Q000627:therapeutic use
D000935:Antifungal Agents; D014230:Triazoles; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D007654:Ketoconazole