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Flucytosine + fluconazole association in the treatment of a murine experimental model of cryptococcosis

Abstract

The efficacy of flucytosine (5-FC) and fluconazole (FLU) association in the treatment of a murine experimental model of cryptococcosis, was evaluated. Seven groups of 10 Balb C mice each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans. Six groups were allocated to receive 5-FC (300 mg/kg) and FLU (16 mg/ kg), either combined and individually, by daily gavage beginning 5 days after the infection, for 2 and 4 weeks. One group received distilled water and was used as control. The evaluation of treatments was based on: survival time; macroscopic examination of brain, lungs, liver and spleen at autopsy; presence of capsulated yeasts in microscopic examination of wet preparations of these organs and cultures of brain homogenate. 5-FC and FLU, individually or combined, significantly prolonged the survival time of the treated animals with respect to the control group (p<0.01). Animals treated for 4 weeks survived significantly longer than those treated for 2 weeks (p<0.01). No significant differences between the animals treated with 5-FC and FLU combined or separately were observed in the survival time and morphological parameters. The association of 5-FC and FLU does not seem to be more effective than 5-FC or FLU alone, in the treatment of this experimental model of cryptococcosis.

Cryptococcosis; Experimental cryptococcosis; Antifungal drugs


BRIEF COMMUNICATION

Flucytosine + fluconazole association in the treatment of a murine experimental model of cryptococcosis

A. J. Bava; R. NegroniI

ICentro de Micología. Facultad de Medicina. Universidad de Buenos Aires. Paraguay 2155, Piso 11. 1121 Buenos Aires, Argentina

SUMMARY

The efficacy of flucytosine (5-FC) and fluconazole (FLU) association in the treatment of a murine experimental model of cryptococcosis, was evaluated.

Seven groups of 10 Balb C mice each, were intraperitoneally inoculated with 107 cells of Cryptococcus neoformans. Six groups were allocated to receive 5-FC (300 mg/kg) and FLU (16 mg/ kg), either combined and individually, by daily gavage beginning 5 days after the infection, for 2 and 4 weeks. One group received distilled water and was used as control.

The evaluation of treatments was based on: survival time; macroscopic examination of brain, lungs, liver and spleen at autopsy; presence of capsulated yeasts in microscopic examination of wet preparations of these organs and cultures of brain homogenate.

5-FC and FLU, individually or combined, significantly prolonged the survival time of the treated animals with respect to the control group (p<0.01). Animals treated for 4 weeks survived significantly longer than those treated for 2 weeks (p<0.01). No significant differences between the animals treated with 5-FC and FLU combined or separately were observed in the survival time and morphological parameters.

The association of 5-FC and FLU does not seem to be more effective than 5-FC or FLU alone, in the treatment of this experimental model of cryptococcosis.

Keywords: Cryptococcosis; Experimental cryptococcosis; Antifungal drugs.

Full text available only in PDF format.

Recebido para publicação em 14/06/1993.

Aceito para publicação em 13/09/1994.

  • 1. ALLENDOERFER, R.; MARQUIS, A.J.; RINALDI, M.G. & GRAYBILL, J.R. - Combinated therapy with fluconazole and flucytosine in murine cryptococcal meningitis. Antimicrob. Agents Chemother., 35: 726-729, 1991.
  • 2. BAVA, A.J. & NEGRONI, R. - Comparative study of 6 antifungal treatments in an experimental model of murine cryptococcosis. Europ. J. Epidem., 8: 422-426, 1992.
  • 3. CHUCK, S.I. & SANDE, M.D. - Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. New Engl. J. Med., 321: 794-799, 1989.
  • 4. DROUHET, E. & DUPONT, B. - Cryptococcosis. In: JACOBS, P.H. & NALL, L. - Antifungal drugs therapy. New York, Marcel Dekker, 1990. p. 143-164.
  • 5. GRAYBILL, J.R. - Future directions of antifungal chemotherapy. Clin. infect. Dis., 14 (suppl. 1): S170 - S181, 1992.
  • 6. HITCHCOCK, C.A.; ANDREWS, R.J.; PYE, G.W. & TROKE, P.F. - Combination therapy of intracranial cryptococcosis in mice with fluconazole (FLU) and 5-fluorocytosine (5-FC) or amphotericin B (Ampho B). (Abstract PS3.58). In: CONGRESS OF THE INTERNATIONAL SOCIETY FOR HUMAN AND ANIMAL MYCOLOGY, 11., Montreal, 1991. Proceedings. p. 135
  • 7. JONES, B.E.; LARSEN, R.A.; BOZZETTE, S. et al. - A phase-II trial of fluconazole + fluocytosine for cryptococcal meningitis (abstract WB 2337). In: INTERNATIONAL CONFERENCE ON AIDS, 7, Florence, 1991. Abstracts. p. 266.
  • 8. LARSEN, R.A.; LEAL, M.A. E. & CHAN, L.S. - Fluconazole compared with amphotericin B plus 5 flucytosine for cryptococcal meningitis in AIDS. Ann. intern. Med., 113: 183-187, 1990.
  • 9. NEGRONI, R. - Micosis en pacientes con SIDA. Rev. argent. Micol., 13: 3-14, 1990.
  • 10. POLAK, A. - Combinations of antifungal agents in the treatment of experimental fungal infections. (Abstract S25.1). In: CONGRESS OF THE INTERNATIONAL SOCIETY FOR HUMAN AND ANIMAL MYCOLOGY, 11, Montreal, 1991. Proceedings. p. 50.
  • 11. SCHEVEN, M.; JUNNEMAN, K.; SCHRAMM, H. & HUHN, W. - Successful treatment of a Candida albicans sepsis with a combination of flucytosine and fluconazole. Mycoses, 35: 315-316, 1992.

Publication Dates

  • Publication in this collection
    05 July 2006
  • Date of issue
    Dec 1994

History

  • Received
    14 June 1993
  • Accepted
    13 Sept 1994
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