We sought to determine whether measurement of Histoplasma capsulatum var. capsulatum
antigen concentration in tissues and blood provided a marker for antifungal effect of
itraconazole in a nonlethal murine model of
histoplasmosis. Treatment with
itraconazole (
Sporanox), in
cyclodextrin, was evaluated in a pulmonary model of
histoplasmosis. Mice infected with 4.0 x 10(7) yeast-phase organisms by endotracheal inoculation were treated with
itraconazole, 1.5 mg twice daily by gavage, for 10 consecutive days, beginning on day 4 of
infection. All mice were sacrificed on day 15 of
infection. Blood, spleen, and lung tissues were removed for culture and quantification of
antigen. Numbers of organisms were significantly lower in spleens from the treated group: 20.8 +/- 41.8 vs. 65.8 +/- 39.1 in the control group, P = 0.017. Numbers of organisms in lung were 9.6 +/- 27.3 colony forming units in treated versus 24.2 +/- 36.3 in control animals, P = 0.267.
Antigen concentrations in spleen tissue and serum were lower in treated versus control mice: spleen, 1.8 +/- .6 units in treated versus 11.0 +/- 2.3 in controls, P < 0.001; serum, 0.8 +/- 0.2 units in treated versus 2.2 +/- 1.0 units in controls, P < 0.001. Lung
antigen concentrations were similar in the two groups, 19.2 +/- 1.4 units in treated compared to 17.9 +/- 3.0 units in control mice, P = 0.142. The
cyclodextrin formulation of
itraconazole (
Sporanox) demonstrated antifungal activity in experimental
histoplasmosis.
Antigen detection was a useful marker for antifungal effect.