Activities of sordarins in murine histoplasmosis

John R. Graybill, Laura Najvar, Annette Fothergill, Rosie Bocanegra, Federico Gomez De Las Heras

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Sordarins are new antifungals which inhibit fungal protein synthesis by blocking elongation factor 2. Three compounds were evaluated in a murine model of histoplasmosis. Immune-competent mice were infected intravenously with 106 to 108 CFU of Histoplasma capsulatum yeast cells. Mice were treated either orally with sordarins or fluconazole from day 2 through 8 after infection or intraperitoneally with amphotericin B during the same period. Protection was measured by increased rates of survival for 30 days after infection or reduction of lung or kidney tissue counts 9 days after infection. All three of the antifungal drugs tested were protective compared with controls. Sordarins were effective at doses as low as 2 mg/kg of body weight/day. This novel class of drugs compared favorably with amphotericin B and fluconazole for the treatment of histoplasmosis.

Original languageEnglish (US)
Pages (from-to)1716-1718
Number of pages3
JournalAntimicrobial agents and chemotherapy
Volume43
Issue number7
DOIs
StatePublished - Jul 1999

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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