Comparative efficacy of fluconazole and amphotericin B in the parenteral treatment of experimental paracoccidioidomycosis in the rat

Patients with severe and complicated paracoccidioidomycosis are treated wit h amphotericin B by the intravenous route. Fluconazole is active in vitro a gainst Paracoccidioides brasiliensis and can also be administered intraveno usly, but few clinical or experimental data are available about its action against the infection caused by this fungus. In the present study, the effi cacy of fluconazole and amphotericin B was assessed comparatively in rats i noculated parenterally with P. brasiliensis. The treatment was performed 3 times a week for 4 weeks starting one week after infection. Fluconazole adm inistered intraperitoneally (14 mg/kg body weight/dose) was more effective (P < 0.001) than amphotericin B (2 mg/kg body weight/dose) in reducing the number of colony forming units in the lungs and spleen. When administered i ntravenously at the dose of 3 mg/kg body weight, fluconazole was as effecti ve as amphotericin B (0.8 mg/kg body weight) in reducing the pulmonary fung al burden. Under these conditions, the rats treated with fluconazole had a smaller number of colony forming units than untreated animals (P < 0.001), but amphotericin B was more effective than fluconazole in reducing spleen i nfection (P < 0.005). Except for this esult obtained with a low dose, fluco nazole showed an antifungal action equal to or higher than that of amphoter icin B. The activity of fluconazole at doses equivalent to those used for h uman treatment suggests that this antifungal agent may be an alternative to amphotericin B for the early intravenous treatment of patients with paraco ccidioidomycosis.