Patients with severe and complicated
paracoccidioidomycosis are treated with
amphotericin B by the intravenous route.
Fluconazole is active in vitro against Paracoccidioides brasiliensis and can also be administered intravenously, but few clinical or experimental data are available about its action against the
infection caused by this fungus. In the present study, the efficacy of
fluconazole and
amphotericin B was assessed comparatively in rats inoculated parenterally with P. brasiliensis. The treatment was performed 3 times a week for 4 weeks starting one week after
infection.
Fluconazole administered 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 intravenously at the dose of 3 mg/kg
body weight,
fluconazole was as effective as
amphotericin B (0.8 mg/kg
body weight) in reducing the pulmonary fungal 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
infection (P < 0.005). Except for this result obtained with a low dose,
fluconazole showed an antifungal action equal to or higher than that of
amphotericin B. The activity of
fluconazole at doses equivalent to those used for human treatment suggests that this
antifungal agent may be an alternative to
amphotericin B for the early intravenous treatment of patients with
paracoccidioidomycosis.