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

• Published in: Revista iberoamericana de micología 2011-12, Vol.28 (4), p.155-158
• Main Authors: Finquelievich, Jorge, Landaburu, Maria Fernanda, Pinoni, Victoria, Iovannitti, Cristina Adela
• Format: Article
• Language: Spanish
• Subjects: Aspergillus; Candida; Histoplasma capsulatum
• ISSN: 1130-1406
• DOI: 10.1016/j.riam.2011.03.006

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 6 mg/Kg/d, caspofungin 2 mg/Kg/d, 4 mg/Kg/d, 8 mg/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.Original Abstract: Antecedentes: La anfotericina B es un farmaco efectivo para el tratamiento de la histoplasmosis. La caspofungina es activa contra especies de Candida y Aspergillus. Estudios in vitro han demostrado el efecto inhibitorio de este farmaco en Histoplasma capsulatum. Objetivo: Evaluar la eficacia de la caspofungina comparada con la anfotericina B para el tratamiento de histoplasmosis en un modelo experimental en hamster. Metodos: Se utilizaron tres cepas de Histoplasma capsulatum var. capsulatum. El tratamiento comenzo una semana tras la inoculacion y los animales fueron distribuidos aleatoriamente en 6 grupos, segun los farmacos utilizados: anfotericina B 6 mg/kg/dia, caspofungina en dosis de 2, 4 y 8 mg/kg/dia, solucion fisiologica y dextrosa al 5%. Se tomaron muestras semanales para hemocult