Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1990 Jun;34(6):1132–1138. doi: 10.1128/aac.34.6.1132

Therapeutic effect of the triazole Bay R 3783 in mouse models of coccidioidomycosis, blastomycosis, and histoplasmosis.

D Pappagianis 1, B L Zimmer 1, G Theodoropoulos 1, M Plempel 1, R F Hector 1
PMCID: PMC171771  PMID: 2393272

Abstract

A new triazole, Bay R 3783, was compared with ketoconazole, itraconazole, and fluconazole, which were given via the alimentary tract at three dosages, and amphotericin B, which was given at 1 mg/kg intraperitoneally, in murine models of the systemic mycoses coccidioidomycosis, histoplasmosis, and blastomycosis. In a pulmonary coccidioidomycosis model, Bay R 3783, fluconazole, and itraconazole were essentially equally efficacious and more active than ketoconazole in protecting mice against death; but they were inferior to amphotericin B. In a short-term organ load experiment, Bay R 3783 and amphotericin B were equally effective and were more effective than the other drugs in reducing the amount of Coccidioides immitis in the lungs. Against meningocerebral coccidioidomycosis, Bay R 3783, itraconazole, and fluconazole at 25 mg/kg and amphotericin B prevented death only during therapy, with mortalities ensuing shortly thereafter. In mice with systemic histoplasmosis, Bay R 3783 and itraconazole at 25 mg/kg and amphotericin B prevented death in all mice through a 44-day observation period. Clearance of Histoplasma capsulatum from organs was similar in mice treated with Bay R 3783 and itraconazole; this clearance was greater than that in mice treated with ketoconazole and fluconazole but less than that in mice treated with amphotericin B. In mice with systemic blastomycosis, Bay R 3783 at 25 mg/kg yielded 90% survivors at 60 days, which was greater than that achieved with amphotericin B (60%) or itraconazole (30%). Clearance of Blastomyces dermatitidis from the lungs was greatest with Bay R 3783, followed by that with amphotericin B, itraconazole, fluconazole, and ketoconazole, in that order. Therefore, Bay R 3783 showed effectiveness comparable to or exceeding those of itraconazole and fluconazole and exceeding that of ketoconazole against these systemic mycoses in mice.

Full text

PDF
1132

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Dupont B., Drouhet E. Cryptococcal meningitis and fluconazole. Ann Intern Med. 1987 May;106(5):778–778. doi: 10.7326/0003-4819-106-5-778_2. [DOI] [PubMed] [Google Scholar]
  2. Fasching C. E., Hughes C. E., Hector R. F., Peterson L. R. High-pressure liquid chromatographic assay of Bay n 7133 in human serum. Antimicrob Agents Chemother. 1984 May;25(5):596–598. doi: 10.1128/aac.25.5.596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Finquelievich J. L., Negroni R., Arechavala A. Treatment with itraconazole of experimental coccidioidomycosis in the Wistar rat. Mycoses. 1988 Feb;31(2):80–86. [PubMed] [Google Scholar]
  4. Graybill J. R., Palou E., Ahrens J. Treatment of murine histoplasmosis with UK 49,858 (fluconazole). Am Rev Respir Dis. 1986 Oct;134(4):768–770. doi: 10.1164/arrd.1986.134.4.768. [DOI] [PubMed] [Google Scholar]
  5. Graybill J. R., Sun S. H., Ahrens J. Treatment of murine coccidioidal meningitis with fluconazole (UK 49,858). J Med Vet Mycol. 1986 Apr;24(2):113–119. doi: 10.1080/02681218680000171. [DOI] [PubMed] [Google Scholar]
  6. Hector R. F., Zimmer B. L., Pappagianis D. Microtiter method for MIC testing with spherule-endospore-phase Coccidioides immitis. J Clin Microbiol. 1988 Dec;26(12):2667–2668. doi: 10.1128/jcm.26.12.2667-2668.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kobayashi G. S., Travis S. J., Medoff G. Comparison of fluconazole and amphotericin B in treating histoplasmosis in immunosuppressed mice. Antimicrob Agents Chemother. 1987 Dec;31(12):2005–2006. doi: 10.1128/aac.31.12.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Levine H. B., Cobb J. M. Oral therapy for experimental coccidioidomycosis with R41 400 (ketoconazole), a new imidazole. Am Rev Respir Dis. 1978 Oct;118(4):715–721. doi: 10.1164/arrd.1978.118.4.715. [DOI] [PubMed] [Google Scholar]
  9. Palou de Fernandez E., Patino M. M., Graybill J. R., Tarbit M. H. Treatment of cryptococcal meningitis in mice with fluconazole. J Antimicrob Chemother. 1986 Aug;18(2):261–270. doi: 10.1093/jac/18.2.261. [DOI] [PubMed] [Google Scholar]
  10. Polak A., Dixon D. M. Fungistatic and fungicidal effects of amphotericin B, ketoconazole and fluconazole (UK 49,858) against histoplasma capsulatum in vitro and in vivo. Mykosen. 1987 Apr;30(4):186–194. doi: 10.1111/j.1439-0507.1987.tb03967.x. [DOI] [PubMed] [Google Scholar]
  11. Shehab Z. M., Britton H., Dunn J. H. Imidazole therapy of coccidioidal meningitis in children. Pediatr Infect Dis J. 1988 Jan;7(1):40–44. doi: 10.1097/00006454-198801000-00010. [DOI] [PubMed] [Google Scholar]
  12. Tucker R. M., Hanson L. H., Brummer E., Stevens D. A. Activity of ICI 195,739, a new oral triazole, compared with that of ketoconazole in the therapy of experimental murine blastomycosis. Antimicrob Agents Chemother. 1989 Apr;33(4):573–575. doi: 10.1128/aac.33.4.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Viviani M. A., Tortorano A. M., Giani P. C., Arici C., Goglio A., Crocchiolo P., Almaviva M. Itraconazole for cryptococcal infection in the acquired immunodeficiency syndrome. Ann Intern Med. 1987 Jan;106(1):166–166. doi: 10.7326/0003-4819-106-1-166_1. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES