Determination of the therapeutic activity of caspofungin compared with the amphotericin B in an animal experimental model of histoplasmosis in hamster (Mesocrisetus auratus)

Abstract

Background: Treatment with amphotericin B is highly effective in histoplasmosis. Caspofungin has shown good activity against Candida and Aspergillus spp. In vitro studies have demonstrated that Histoplasma capsulatum is inhibited by caspofungin.

Objectives: The purpose of this study was to evaluate the effectiveness of caspofungin in the treatment of histoplasmosis in an animal experimental model.

Methods: Three strains of Histoplasma capsulatum var. capsulatum were used. Treatment started one week post-inoculation and the animals were randomly assigned to six groups: amphotericin B 6mg/Kg/d, caspofungin 2mg/Kg/d, 4mg/Kg/d, 8mg/Kg/d and the other two groups received saline solution and dextrose solution. Blood samples for culture were obtained once a week, from day 7 to 35 post-inoculation. One week after the end of the treatment the animals were sacrificed and spleen cultures were performed.

Results: Blood cultures were negative in all the hamsters which received amphotericin B (100%, P<0.001); those treated with caspofungin and the control animals presented 30 and 32% of positive cultures respectively (P=0.59). Spleen cultures were negative in the animals treated with amphotericin B, while the percentage of positive spleen cultures in the caspofungin groups varied from 25 to 100%, and in the control groups from 35 to 94.8% (P=0.07). The statistical analysis of the undiluted cultures showed the use of amphotericin B as the only independent predictor of negative culture (P<0.001).

Conclusions: The efficacy of amphotericin B is well known for the treatment of histoplasmosis, though we could not demonstrate that caspofungin is better than control.