Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1989 Aug;33(8):1242–1246. doi: 10.1128/aac.33.8.1242

Efficacy of SCH39304 in murine cryptococcosis.

B I Restrepo 1, J Ahrens 1, J R Graybill 1
PMCID: PMC172633  PMID: 2552903

Abstract

Cryptococcal meningitis is increasing in frequency, in large part because of the advent of acquired immune deficiency syndrome. Using the murine cryptococcosis model, a new oral triazole, SCH39304, has been compared with two drugs in clinical use, fluconazole and amphotericin B. BALB/c mice (nu/nu and nu/+) were challenged intracerebrally or intranasally. Oral treatment was given daily with SCH39304 at doses of 1 to 60 mg/kg of body weight or fluconazole at doses of 1 or 5 mg/kg of body weight. Amphotericin B was given intraperitoneally three times weekly, at doses of 3 or 6 mg/kg. After intracerebral challenge, SCH39304 prolonged survival in doses as low as 1 mg/kg, a dose at which fluconazole was ineffective. At equal doses, SCH39304 consistently increased survival more than did fluconazole but not longer than did amphotericin B. SCH39304 significantly lowered colony counts in brains more than did fluconazole but no more than did amphotericin B. SCH39304 was also superior to fluconazole after intranasal challenge at equal doses. SCH39304 appears to be superior to fluconazole in mice when the drugs are given at equal doses. Clinical trials are warranted.

Full text

PDF
1242

Selected References

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

  1. Arndt C. A., Walsh T. J., McCully C. L., Balis F. M., Pizzo P. A., Poplack D. G. Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system. J Infect Dis. 1988 Jan;157(1):178–180. doi: 10.1093/infdis/157.1.178. [DOI] [PubMed] [Google Scholar]
  2. Bennett J. E., Dismukes W. E., Duma R. J., Medoff G., Sande M. A., Gallis H., Leonard J., Fields B. T., Bradshaw M., Haywood H. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis. N Engl J Med. 1979 Jul 19;301(3):126–131. doi: 10.1056/NEJM197907193010303. [DOI] [PubMed] [Google Scholar]
  3. Byrne W. R., Wajszczuk C. P. Cryptococcal meningitis in the acquired immunodeficiency syndrome (AIDS): successful treatment with fluconazole after failure of amphotericin B. Ann Intern Med. 1988 Mar;108(3):384–385. doi: 10.7326/0003-4819-108-3-384. [DOI] [PubMed] [Google Scholar]
  4. Diamond R. D., Bennett J. E. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med. 1974 Feb;80(2):176–181. doi: 10.7326/0003-4819-80-2-176. [DOI] [PubMed] [Google Scholar]
  5. Dismukes W. E., Cloud G., Gallis H. A., Kerkering T. M., Medoff G., Craven P. C., Kaplowitz L. G., Fisher J. F., Gregg C. R., Bowles C. A. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med. 1987 Aug 6;317(6):334–341. doi: 10.1056/NEJM198708063170602. [DOI] [PubMed] [Google Scholar]
  6. Doern G. V., Tubert T. A., Chapin K., Rinaldi M. G. Effect of medium composition on results of macrobroth dilution antifungal susceptibility testing of yeasts. J Clin Microbiol. 1986 Oct;24(4):507–511. doi: 10.1128/jcm.24.4.507-511.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eng R. H., Bishburg E., Smith S. M., Kapila R. Cryptococcal infections in patients with acquired immune deficiency syndrome. Am J Med. 1986 Jul;81(1):19–23. doi: 10.1016/0002-9343(86)90176-2. [DOI] [PubMed] [Google Scholar]
  8. Goodpasture H. C., Hershberger R. E., Barnett A. M., Peterie J. D. Treatment of central nervous system fungal infection with ketoconazole. Arch Intern Med. 1985 May;145(5):879–880. [PubMed] [Google Scholar]
  9. Graybill J. R., Ahrens J. R 51211 (itraconazole) therapy of murine cryptococcosis. Sabouraudia. 1984;22(6):445–453. doi: 10.1080/00362178485380721. [DOI] [PubMed] [Google Scholar]
  10. Graybill J. R., Craven P. C., Taylor R. L., Williams D. M., Magee W. E. Treatment of murine cryptococcosis with liposome-associated amphotericin B. J Infect Dis. 1982 May;145(5):748–752. doi: 10.1093/infdis/145.2.748. [DOI] [PubMed] [Google Scholar]
  11. Graybill J. R., Williams D. M., Van Cutsem E., Drutz D. J. Combination therapy of experimental histoplasmosis and cryptococcosis with amphotericin B and ketoconazole. Rev Infect Dis. 1980 Jul-Aug;2(4):551–558. doi: 10.1093/clinids/2.4.551. [DOI] [PubMed] [Google Scholar]
  12. Kovacs J. A., Kovacs A. A., Polis M., Wright W. C., Gill V. J., Tuazon C. U., Gelmann E. P., Lane H. C., Longfield R., Overturf G. Cryptococcosis in the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Oct;103(4):533–538. doi: 10.7326/0003-4819-103-4-533. [DOI] [PubMed] [Google Scholar]
  13. Lake-Bakaar G., Quadros E., Beidas S., Elsakr M., Tom W., Wilson D. E., Dincsoy H. P., Cohen P., Straus E. W. Gastric secretory failure in patients with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1988 Sep 15;109(6):502–504. doi: 10.7326/0003-4819-109-6-502. [DOI] [PubMed] [Google Scholar]
  14. Stern J. J., Hartman B. J., Sharkey P., Rowland V., Squires K. E., Murray H. W., Graybill J. R. Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients. Am J Med. 1988 Oct;85(4):477–480. doi: 10.1016/s0002-9343(88)80081-0. [DOI] [PubMed] [Google Scholar]
  15. Washington J. A., 2nd Discrepancies between in vitro activity of and in vivo response to antimicrobial agents. Diagn Microbiol Infect Dis. 1983 Mar;1(1):25–31. doi: 10.1016/0732-8893(83)90029-9. [DOI] [PubMed] [Google Scholar]
  16. Zuger A., Louie E., Holzman R. S., Simberkoff M. S., Rahal J. J. Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Diagnostic features and outcome of treatment. Ann Intern Med. 1986 Feb;104(2):234–240. doi: 10.7326/0003-4819-104-2-234. [DOI] [PubMed] [Google Scholar]

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

RESOURCES