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

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.