Skip to main content
Applied Microbiology logoLink to Applied Microbiology
. 1970 Oct;20(4):624–629. doi: 10.1128/am.20.4.624-629.1970

Evaluation of Systemic Antifungal Agents in X-Irradiated Mice 1

Robert S Gordee 1, Thomas R Matthews 1,2
PMCID: PMC377004  PMID: 5498613

Abstract

The effect of X irradiation on the survival time of animals experimentally infected with pathogenic fungi was studied, and the activity of antifungal agents in pre-irradiated hosts was evaluated. A 24-hr preinfection dose of X irradiation decreased the survival time of mice infected with Cryptococcus neoformans and Histoplasma capsulatum to a greater extent than Candida albicans or Blastomyces dermatitidis infections. Exposure to 400 r caused a significant reduction in the variation (S2) survival time of C. albicans or H. capsulatum mouse infections. A single 100-mg/kg dose of 5-fluorocytosine or amphotericin B administered within 24 hr postinfection significantly extended the survival time of mice infected with C. albicans. Delayed treatment with amphotericin B was effective against C. neoformans infections. Four 50-mg/kg doses of 5-fluorocytosine were more effective than a single 200-mg/kg dose against C. neoformans infections. A single dose of amphotericin B provided significant protection when administered 48 hr postinfection against B. dermatitidis in preirradiated mice. A single dose of saramycetin 48 hr postinfection was highly effective against H. capsulatum mouse infections. A 100-mg/kg dose of amphotericin B was only effective against this fungal pathogen when administered within 8 hr postinfection. In vivo activity of the antifungal agents studied was detected within 8 to 14 days. The relative in vivo activity of several antifungal agents indicated the importance of considering their individual pharmacological properties for optimum effectiveness. The experimental model used in this study should be useful for the detection and for the preclinical evaluation of new antifungal agents.

Full text

PDF
624

Selected References

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

  1. EMMONS C. W. Chemotherapeutic and toxic activity of the antifungal agent X-5079C in experimental mycoses. Am Rev Respir Dis. 1961 Oct;84:507–513. doi: 10.1164/arrd.1961.84.4.507. [DOI] [PubMed] [Google Scholar]
  2. Gordee R. S., Matthews T. R. Reliable technique for plating pathogenic fungi from organ homogenates. Appl Microbiol. 1968 Oct;16(10):1610–1610. doi: 10.1128/am.16.10.1610-.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gordee R. S., Simpson P. J. Relationships of x-irradiation to the enhancement of Candida albicans infections. J Bacteriol. 1967 Jul;94(1):6–12. doi: 10.1128/jb.94.1.6-12.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hurley R. Experimental infection with Candida albicans in modified hosts. J Pathol Bacteriol. 1966 Jul;92(1):57–67. doi: 10.1002/path.1700920108. [DOI] [PubMed] [Google Scholar]
  5. Kimball H. R., Williams T. W., Wolff S. M. Effect of bacterial endotoxin on experimental fungal infections. J Immunol. 1968 Jan;100(1):24–33. [PubMed] [Google Scholar]
  6. Koechlin B. A., Rubio F., Palmer S., Gabriel T., Duschinsky R. The metabolism of 5-fluorocytosine-2-14-C and of cytosine-14-C in the rat and the disposition of 5-fluorocytosine-2-14-C in man. Biochem Pharmacol. 1966 Apr;15(4):435–446. doi: 10.1016/0006-2952(66)90254-1. [DOI] [PubMed] [Google Scholar]
  7. LOURIA D. B. Some aspects of the absorption, distribution, and excretion of amphotericin B in man. Antibiotic Med Clin Ther (New York) 1958 May;5(5):295–301. [PubMed] [Google Scholar]
  8. Lones G. W., Pggott W. R., Hill W. B. Effect of neohepataene on experimental systemic mycoses in mice. Sabouraudia. 1968 Oct;6(4):334–338. doi: 10.1080/00362176885190651. [DOI] [PubMed] [Google Scholar]
  9. MILLER C. P., HAMMOND C. W., ANDERLE S. K. Studies on susceptibility to infection following ionizing radiation. V. Comparison of intraperitoneal and intravenous challenge at intervals following different doses of x-radiation. J Exp Med. 1960 Jun 1;111:773–784. doi: 10.1084/jem.111.6.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Panse M. V. Enhancement of Candida albicans virulence in mice infection & efficacy of hamycin. Indian J Exp Biol. 1967 Apr;5(2):112–114. [PubMed] [Google Scholar]
  11. Pittillo R. F., Ray B. J. Chemotherapeutic activity of 5-fluorocytosine against a lethal Candida albicans infection in mice. Appl Microbiol. 1969 May;17(5):773–774. doi: 10.1128/am.17.5.773-774.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. ROTH F. J., Jr, FRIEDMAN J., SYVERTON J. T. Effects of roentgen radiation and cortisone on susceptibility of mice to Candida albicans. J Immunol. 1957 Feb;78(2):122–127. [PubMed] [Google Scholar]
  13. Scholer H. J. Sulfonamides in experimental nocardiosis, histoplasmosis, and South American blastomycosis. Chemotherapy. 1968;13(2):65–80. doi: 10.1159/000220533. [DOI] [PubMed] [Google Scholar]
  14. Seelig M. S. Mechanisms by which antibiotics increase the incidence and severity of candidiasis and alter the immunological defenses. Bacteriol Rev. 1966 Jun;30(2):442–459. doi: 10.1128/br.30.2.442-459.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Shadomy S., Robertson G. M., Jr, Shadomy H. J., Utz J. P., Gamble E. In vitro and in vivo activity of hamycin against Blastomyces dermatitidis. J Bacteriol. 1969 Feb;97(2):481–487. doi: 10.1128/jb.97.2.481-487.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. TALMAGE D. W. Effect of ionizing radiation on resistance and infection. Annu Rev Microbiol. 1955;9:335–346. doi: 10.1146/annurev.mi.09.100155.002003. [DOI] [PubMed] [Google Scholar]
  17. WICK W. E., STREIGHTOFF F., HOLMES D. H. Guide to antibiotic therapy of experimental bacterial infections in mice. J Bacteriol. 1961 Feb;81:233–235. doi: 10.1128/jb.81.2.233-235.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Williams T. W., Jr, Emmons C. W. Hamycin treatment of experimental blastomycosis in mice. Proc Soc Exp Biol Med. 1965 Nov;120(2):481–484. doi: 10.3181/00379727-120-30567. [DOI] [PubMed] [Google Scholar]

Articles from Applied Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES