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. 1989 Feb;33(2):147–151. doi: 10.1128/aac.33.2.147

Comparison of the efficacies of amphotericin B, fluconazole, and itraconazole against a systemic Candida albicans infection in normal and neutropenic mice.

J W Van t Wout 1, H Mattie 1, R van Furth 1
PMCID: PMC171446  PMID: 2541654

Abstract

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.

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Selected References

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  1. Bistoni F., Vecchiarelli A., Mazzolla R., Puccetti P., Marconi P., Garaci E. Immunoadjuvant activity of amphotericin B as displayed in mice infected with Candida albicans. Antimicrob Agents Chemother. 1985 Apr;27(4):625–631. doi: 10.1128/aac.27.4.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Espinel-Ingroff A., Shadomy S., Gebhart R. J. In vitro studies with R 51,211 (itraconazole). Antimicrob Agents Chemother. 1984 Jul;26(1):5–9. doi: 10.1128/aac.26.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fainstein V., Bodey G. P., Elting L., Maksymiuk A., Keating M., McCredie K. B. Amphotericin B or ketoconazole therapy of fungal infections in neutropenic cancer patients. Antimicrob Agents Chemother. 1987 Jan;31(1):11–15. doi: 10.1128/aac.31.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ganer A., Arathoon E., Stevens D. A. Initial experience in therapy for progressive mycoses with itraconazole, the first clinically studied triazole. Rev Infect Dis. 1987 Jan-Feb;9 (Suppl 1):S77–S86. doi: 10.1093/clinids/9.supplement_1.s77. [DOI] [PubMed] [Google Scholar]
  5. Horn R., Wong B., Kiehn T. E., Armstrong D. Fungemia in a cancer hospital: changing frequency, earlier onset, and results of therapy. Rev Infect Dis. 1985 Sep-Oct;7(5):646–655. doi: 10.1093/clinids/7.5.646. [DOI] [PubMed] [Google Scholar]
  6. Hughes C. E., Beggs W. H. Action of fluconazole (UK-49,858) in relation to other systemic antifungal azoles. J Antimicrob Chemother. 1987 Feb;19(2):171–174. doi: 10.1093/jac/19.2.171. [DOI] [PubMed] [Google Scholar]
  7. Hughes C. E., Peterson L. R., Beggs W. H., Gerding D. N. Ketoconazole and flucytosine alone and in combination against Candida spp. in a neutropenic site in rabbits. J Antimicrob Chemother. 1986 Jul;18(1):65–72. doi: 10.1093/jac/18.1.65. [DOI] [PubMed] [Google Scholar]
  8. Humphrey M. J., Jevons S., Tarbit M. H. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother. 1985 Nov;28(5):648–653. doi: 10.1128/aac.28.5.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lopez-Berestein G., Fainstein V., Hopfer R., Mehta K., Sullivan M. P., Keating M., Rosenblum M. G., Mehta R., Luna M., Hersh E. M. Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study. J Infect Dis. 1985 Apr;151(4):704–710. doi: 10.1093/infdis/151.4.704. [DOI] [PubMed] [Google Scholar]
  10. Lopez-Berestein G., Hopfer R. L., Mehta R., Mehta K., Hersh E. M., Juliano R. L. Liposome-encapsulated amphotericin B for treatment of disseminated candidiasis in neutropenic mice. J Infect Dis. 1984 Aug;150(2):278–283. doi: 10.1093/infdis/150.2.278. [DOI] [PubMed] [Google Scholar]
  11. Odds F. C., Cheesman S. L., Abbott A. B. Antifungal effects of fluconazole (UK 49858), a new triazole antifungal, in vitro. J Antimicrob Chemother. 1986 Oct;18(4):473–478. doi: 10.1093/jac/18.4.473. [DOI] [PubMed] [Google Scholar]
  12. Perfect J. R., Savani D. V., Durack D. T. Comparison of itraconazole and fluconazole in treatment of cryptococcal meningitis and candida pyelonephritis in rabbits. Antimicrob Agents Chemother. 1986 Apr;29(4):579–583. doi: 10.1128/aac.29.4.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rabinovich S., Shaw B. D., Bryant T., Donta S. T. Effect of 5-fluorocytosine and amphotericin B on Candida albicans infection in mice. J Infect Dis. 1974 Jul;130(1):28–31. doi: 10.1093/infdis/130.1.28. [DOI] [PubMed] [Google Scholar]
  14. Richardson K., Brammer K. W., Marriott M. S., Troke P. F. Activity of UK-49,858, a bis-triazole derivative, against experimental infections with Candida albicans and Trichophyton mentagrophytes. Antimicrob Agents Chemother. 1985 May;27(5):832–835. doi: 10.1128/aac.27.5.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rogers T. E., Galgiani J. N. Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo. Antimicrob Agents Chemother. 1986 Sep;30(3):418–422. doi: 10.1128/aac.30.3.418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Saag M. S., Dismukes W. E. Azole antifungal agents: emphasis on new triazoles. Antimicrob Agents Chemother. 1988 Jan;32(1):1–8. doi: 10.1128/aac.32.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tremblay C., Barza M., Fiore C., Szoka F. Efficacy of liposome-intercalated amphotericin B in the treatment of systemic candidiasis in mice. Antimicrob Agents Chemother. 1984 Aug;26(2):170–173. doi: 10.1128/aac.26.2.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Troke P. F., Andrews R. J., Brammer K. W., Marriott M. S., Richardson K. Efficacy of UK-49,858 (fluconazole) against Candida albicans experimental infections in mice. Antimicrob Agents Chemother. 1985 Dec;28(6):815–818. doi: 10.1128/aac.28.6.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Van Cutsem J., Fransen J., Janssen P. A. Therapeutic efficacy of itraconazole in systemic candidosis in guinea pigs. Chemotherapy. 1987;33(1):52–60. doi: 10.1159/000238475. [DOI] [PubMed] [Google Scholar]
  20. Van't Wout J. W., Mattie H., van Furth R. A prospective study of the efficacy of fluconazole (UK-49,858) against deep-seated fungal infections. J Antimicrob Chemother. 1988 May;21(5):665–672. doi: 10.1093/jac/21.5.665. [DOI] [PubMed] [Google Scholar]
  21. Weber M. J., Keppen M., Gawith K. E., Epstein R. B. Treatment of systemic candidiasis in neutropenic dogs with ketoconazole. Exp Hematol. 1985 Sep;13(8):791–795. [PubMed] [Google Scholar]

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