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. 1996 Oct;40(10):2243–2247. doi: 10.1128/aac.40.10.2243

Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis.

K Hata 1, J Kimura 1, H Miki 1, T Toyosawa 1, M Moriyama 1, K Katsu 1
PMCID: PMC163511  PMID: 8891122

Abstract

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. In the present study, we investigated the therapeutic effects of oral ER-30346 on experimental local infections caused by Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans and compared them with those of itraconazole and fluconazole. In experimental murine models of pulmonary aspergillosis, candidiasis, and cryptococcosis, ER-30346 reduced the numbers of CFU in the lungs significantly compared with the numbers of CFU in the lungs of the controls (P < 0.05). ER-30346 was as effective as or more effective than itraconazole against pulmonary aspergillosis. Against pulmonary candidiasis and cryptococcosis, ER-30346 was more effective than itraconazole and was as effective as fluconazole. ER-30346 was also effective against pulmonary candidiasis caused by fluconazole-resistant C. albicans. In mice with intracranial cryptococcosis, ER-30346 reduced the numbers of CFU in the brains significantly compared with the numbers of CFU in the brains of the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. In an experimental model of oral candidiasis in rats, ER-30346 reduced the numbers of CFU in oral swabs significantly compared with the numbers of CFU in oral swabs from the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. Thus, ER-30346 shows efficacy in murine aspergillosis, candidiasis, and cryptococcosis models. Further studies are needed to determine the potential of ER-30346 for use in the treatment of these infections.

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Selected References

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  1. Allendoerfer R., Loebenberg D., Rinaldi M. G., Graybill J. R. Evaluation of SCH51048 in an experimental model of pulmonary aspergillosis. Antimicrob Agents Chemother. 1995 Jun;39(6):1345–1348. doi: 10.1128/aac.39.6.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barchiesi F., Colombo A. L., McGough D. A., Fothergill A. W., Rinaldi M. G. In vitro activity of itraconazole against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus. Antimicrob Agents Chemother. 1994 Jul;38(7):1530–1533. doi: 10.1128/aac.38.7.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DeGregorio M. W., Lee W. M., Linker C. A., Jacobs R. A., Ries C. A. Fungal infections in patients with acute leukemia. Am J Med. 1982 Oct;73(4):543–548. doi: 10.1016/0002-9343(82)90334-5. [DOI] [PubMed] [Google Scholar]
  4. Denning D. W., Lee J. Y., Hostetler J. S., Pappas P., Kauffman C. A., Dewsnup D. H., Galgiani J. N., Graybill J. R., Sugar A. M., Catanzaro A. NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis. Am J Med. 1994 Aug;97(2):135–144. doi: 10.1016/0002-9343(94)90023-x. [DOI] [PubMed] [Google Scholar]
  5. Denning D. W., Tucker R. M., Hanson L. H., Stevens D. A. Treatment of invasive aspergillosis with itraconazole. Am J Med. 1989 Jun;86(6 Pt 2):791–800. doi: 10.1016/0002-9343(89)90475-0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Georgopapadakou N. H., Walsh T. J. Antifungal agents: chemotherapeutic targets and immunologic strategies. Antimicrob Agents Chemother. 1996 Feb;40(2):279–291. doi: 10.1128/aac.40.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Graybill J. R. New antifungal agents. Eur J Clin Microbiol Infect Dis. 1989 May;8(5):402–412. doi: 10.1007/BF01964056. [DOI] [PubMed] [Google Scholar]
  9. Hata K., Kimura J., Miki H., Toyosawa T., Nakamura T., Katsu K. In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum. Antimicrob Agents Chemother. 1996 Oct;40(10):2237–2242. doi: 10.1128/aac.40.10.2237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hay R. J. Antifungal therapy and the new azole compounds. J Antimicrob Chemother. 1991 Jul;28 (Suppl A):35–46. doi: 10.1093/jac/28.suppl_a.35. [DOI] [PubMed] [Google Scholar]
  11. He X., Tiballi R. N., Zarins L. T., Bradley S. F., Sangeorzan J. A., Kauffman C. A. Azole resistance in oropharyngeal Candida albicans strains isolated from patients infected with human immunodeficiency virus. Antimicrob Agents Chemother. 1994 Oct;38(10):2495–2497. doi: 10.1128/aac.38.10.2495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hector R. F., Yee E. Evaluation of Bay R 3783 in rodent models of superficial and systemic candidiasis, meningeal cryptococcosis, and pulmonary aspergillosis. Antimicrob Agents Chemother. 1990 Mar;34(3):448–454. doi: 10.1128/aac.34.3.448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hitchcock C. A., Pye G. W., Troke P. F., Johnson E. M., Warnock D. W. Fluconazole resistance in Candida glabrata. Antimicrob Agents Chemother. 1993 Sep;37(9):1962–1965. doi: 10.1128/aac.37.9.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoag K. A., Street N. E., Huffnagle G. B., Lipscomb M. F. Early cytokine production in pulmonary Cryptococcus neoformans infections distinguishes susceptible and resistant mice. Am J Respir Cell Mol Biol. 1995 Oct;13(4):487–495. doi: 10.1165/ajrcmb.13.4.7546779. [DOI] [PubMed] [Google Scholar]
  15. Huffnagle G. B., Strieter R. M., Standiford T. J., McDonald R. A., Burdick M. D., Kunkel S. L., Toews G. B. The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of monocytes and CD4+ T cells during a pulmonary Cryptococcus neoformans infection. J Immunol. 1995 Nov 15;155(10):4790–4797. [PubMed] [Google Scholar]
  16. Jones J. H., Russell C. The histology of chronic candidal infection of the rat's tongue. J Pathol. 1974 Jun;113(2):97–100. doi: 10.1002/path.1711130205. [DOI] [PubMed] [Google Scholar]
  17. Larsen R. A. Azoles and AIDS. J Infect Dis. 1990 Sep;162(3):727–730. doi: 10.1093/infdis/162.3.727. [DOI] [PubMed] [Google Scholar]
  18. Meyer R. D., Young L. S., Armstrong D., Yu B. Aspergillosis complicating neoplastic disease. Am J Med. 1973 Jan;54(1):6–15. doi: 10.1016/0002-9343(73)90077-6. [DOI] [PubMed] [Google Scholar]
  19. Myerowitz R. L., Pazin G. J., Allen C. M. Disseminated candidiasis. Changes in incidence, underlying diseases, and pathology. Am J Clin Pathol. 1977 Jul;68(1):29–38. doi: 10.1093/ajcp/68.1.29. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Sawyer R. T. Experimental pulmonary candidiasis. Mycopathologia. 1990 Feb;109(2):99–109. doi: 10.1007/BF00436790. [DOI] [PubMed] [Google Scholar]
  22. Sawyer R. T., Harmsen A. G. The relative contribution of resident pulmonary alveolar macrophage and inflammatory polymorphonuclear neutrophils in host resistance to pulmonary infection by Candida albicans. Mycopathologia. 1989 Nov;108(2):95–105. doi: 10.1007/BF00436059. [DOI] [PubMed] [Google Scholar]
  23. Uchida K., Yamaguchi H., Shibuya K. [The therapeutic effects of itraconazole, a new triazole antifungal agent, for experimental fungal infections]. Jpn J Antibiot. 1991 May;44(5):588–599. [PubMed] [Google Scholar]
  24. Van Cutsem J., Van Gerven F., Van de Ven M. A., Borgers M., Janssen P. A. Itraconazole, a new triazole that is orally active in aspergillosis. Antimicrob Agents Chemother. 1984 Oct;26(4):527–534. doi: 10.1128/aac.26.4.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Van Zant G. Studies of hematopoietic stem cells spared by 5-fluorouracil. J Exp Med. 1984 Mar 1;159(3):679–690. doi: 10.1084/jem.159.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Venkateswarlu K., Denning D. W., Manning N. J., Kelly S. L. Resistance to fluconazole in Candida albicans from AIDS patients correlated with reduced intracellular accumulation of drug. FEMS Microbiol Lett. 1995 Sep 15;131(3):337–341. doi: 10.1111/j.1574-6968.1995.tb07797.x. [DOI] [PubMed] [Google Scholar]
  27. vanden Bossche H., Marichal P., Odds F. C., Le Jeune L., Coene M. C. Characterization of an azole-resistant Candida glabrata isolate. Antimicrob Agents Chemother. 1992 Dec;36(12):2602–2610. doi: 10.1128/aac.36.12.2602. [DOI] [PMC free article] [PubMed] [Google Scholar]

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