Activities of sordarins in murine histoplasmosis

Sordarins are new antifungals which inhibit fungal protein synthesis by blo cking elongation factor 2. Three compounds were evaluated in a murine model of histoplasmosis. Immune competent mice were infected intravenously with 10(6) to 10(8) CFU of Histoplasma capsulatum yeast cells. Mice were treated either orally with sordarins or fluconazole from day 2 through 8 after inf ection or intraperitoneally with amphotericin B during the same period. Pro tection was measured by increased rates of survival for 30 days after infec tion or reduction of lung or kidney tissue counts 9 days after infection. A ll three of the antifungal drugs tested were protective compared with contr ols. 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 fluc onazole for the treatment of histoplasmosis.