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. 1997 Jul;41(7):1558–1561. doi: 10.1128/aac.41.7.1558

Activity of the triazole SCH 56592 against disseminated murine coccidioidomycosis.

J E Lutz 1, K V Clemons 1, B H Aristizabal 1, D A Stevens 1
PMCID: PMC163958  PMID: 9210684

Abstract

SCH 56592 (SCH) is a new triazole antifungal with a broad spectrum of activity. In vitro susceptibility testing against five strains of Coccidioides immitis revealed MICs from 0.39 to 3.13 microg/ml and minimal fungicidal concentrations from 1.56 to 3.13 microg/ml. A murine model of systemic coccidioidomycosis was established in female CD-1 mice. Groups received either no treatment or oral therapy with fluconazole at 10 or 100 mg/kg of body weight; itraconazole at 10 or 100 mg/kg; SCH at 0.5, 2, 10, or 25 mg/kg; or its methylcellulose diluent alone. Therapy began 2 days postinfection and continued once daily for 19 days. Surviving mice were euthanized 49 days postinfection, and infectious burdens were determined by culture. All drugs were superior to no-treatment or diluent-treatment controls (P < 0.001) in prolonging survival but were not significantly different from one another. Itraconazole at 100 mg/kg was superior to fluconazole in reduction of CFU in the spleen, liver, and lung (P < 0.01 to 0.001). SCH at 0.5 mg/kg was superior to either fluconazole or itraconazole at 10 mg/kg in reduction of CFU in all three organs (P < 0.05 to 0.001). SCH at 2 mg/kg was not significantly different from itraconazole at 100 mg/kg in all three organs. SCH at 10 and 25 mg/kg was superior to either dose of fluconazole or itraconazole in all three organs (P < 0.05 to 0.001). In terms of reduction of CFU, SCH was > or = 200-fold as potent as fluconazole and > or = 50-fold as potent as itraconazole. There was a clear dose-responsive relationship for SCH in each of the organs. It is noteworthy that SCH effected cures (no detectable C. immitis in any organ) in 1 of 9, 6 of 10, or 9 of 9 surviving mice in animals given 2, 10, or 25 mg/kg, respectively. Neither fluconazole nor itraconazole cured any survivor. SCH has potent, fungicidal activity in vivo against C. immitis. It should be considered for clinical trials in patients with coccidioidomycosis.

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Selected References

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

  1. Clemons K. V., Hanson L. H., Perlman A. M., Stevens D. A. Efficacy of SCH39304 and fluconazole in a murine model of disseminated coccidioidomycosis. Antimicrob Agents Chemother. 1990 May;34(5):928–930. doi: 10.1128/aac.34.5.928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clemons K. V., Homola M. E., Stevens D. A. Activities of the triazole SCH 51048 against Coccidioides immitis in vitro and in vivo. Antimicrob Agents Chemother. 1995 May;39(5):1169–1172. doi: 10.1128/aac.39.5.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clemons K. V., Leathers C. R., Lee K. W. Systemic Coccidioides immitis infection in nude and beige mice. Infect Immun. 1985 Mar;47(3):814–821. doi: 10.1128/iai.47.3.814-821.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clemons K. V., Stevens D. A. Comparative efficacy of amphotericin B colloidal dispersion and amphotericin B deoxycholate suspension in treatment of murine coccidioidomycosis. Antimicrob Agents Chemother. 1991 Sep;35(9):1829–1833. doi: 10.1128/aac.35.9.1829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clemons K. V., Stevens D. A. Efficacies of amphotericin B lipid complex (ABLC) and conventional amphotericin B against murine coccidioidomycosis. J Antimicrob Chemother. 1992 Sep;30(3):353–363. doi: 10.1093/jac/30.3.353. [DOI] [PubMed] [Google Scholar]
  6. Clemons K. V., Stevens D. A. Utility of the triazole D0870 in the treatment of experimental systemic coccidioidomycosis. J Med Vet Mycol. 1994;32(4):323–326. doi: 10.1080/02681219480000411. [DOI] [PubMed] [Google Scholar]
  7. Dewsnup D. H., Galgiani J. N., Graybill J. R., Diaz M., Rendon A., Cloud G. A., Stevens D. A. Is it ever safe to stop azole therapy for Coccidioides immitis meningitis? Ann Intern Med. 1996 Feb 1;124(3):305–310. doi: 10.7326/0003-4819-124-3-199602010-00004. [DOI] [PubMed] [Google Scholar]
  8. Einstein H. E., Johnson R. H. Coccidioidomycosis: new aspects of epidemiology and therapy. Clin Infect Dis. 1993 Mar;16(3):349–354. doi: 10.1093/clind/16.3.349. [DOI] [PubMed] [Google Scholar]
  9. Galgiani J. N., Ampel N. M. Coccidioidomycosis in human immunodeficiency virus-infected patients. J Infect Dis. 1990 Nov;162(5):1165–1169. doi: 10.1093/infdis/162.5.1165. [DOI] [PubMed] [Google Scholar]
  10. Hoeprich P. D., Finn P. D. Obfuscation of the activity of antifungal antimicrobics by culture media. J Infect Dis. 1972 Oct;126(4):353–361. doi: 10.1093/infdis/126.4.353. [DOI] [PubMed] [Google Scholar]
  11. Hostetler J. S., Catanzaro A., Stevens D. A., Graybill J. R., Sharkey P. K., Larsen R. A., Tucker R. M., al-Haidary A. D., Rinaldi M. G., Cloud G. A. Treatment of coccidioidomycosis with SCH 39304. J Med Vet Mycol. 1994;32(2):105–114. doi: 10.1080/02681219480000151. [DOI] [PubMed] [Google Scholar]
  12. Hostetler J. S., Hanson L. H., Stevens D. A. Effect of cyclodextrin on the pharmacology of antifungal oral azoles. Antimicrob Agents Chemother. 1992 Feb;36(2):477–480. doi: 10.1128/aac.36.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Stevens D. A. Coccidioidomycosis. N Engl J Med. 1995 Apr 20;332(16):1077–1082. doi: 10.1056/NEJM199504203321607. [DOI] [PubMed] [Google Scholar]
  14. Sugar A. M., Liu X. P. In vitro and in vivo activities of SCH 56592 against Blastomyces dermatitidis. Antimicrob Agents Chemother. 1996 May;40(5):1314–1316. doi: 10.1128/aac.40.5.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]

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