Activities of sordarins in murine histoplasmosis.
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 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 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.
Graybill
J R
JR
University of Texas Health Science Center, San Antonio, Texas. graybill@uthSCSA.edu
Najvar
L
L
Fothergill
A
A
Bocanegra
R
R
de las Heras
F G
FG
D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use* / Q000633:toxicity; D015725:Fluconazole / Q000627:therapeutic use; D006658:Histoplasma / Q000302:isolation & purification; D006660:Histoplasmosis / Q000188:drug therapy* / Q000382:microbiology; D007192:Indenes; D007668:Kidney / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D000935:Antifungal Agents; D007192:Indenes; C003329:sordarin; D000666:Amphotericin B; D015725:Fluconazole