There are no effective therapeutics for treating invasive Scedosporium prolificans infections. Doses of 15, 25, and 50 mg/kg of body weight/day for the new triazole albaconazole (ABC) were evaluated in an immunocompetent rabbit model of systemic infection with this mold. Treatments were begun 1 day after challenge and given for 10 days. ABC at any dose was more effective than amphotericin B (AMB) at 0.8 mg/kg/day at clearing S. prolificans from tissue (P < 0.007). The percentages of survival at 25 mg of ABC/kg/day were similar to those obtained with AMB. Rabbits showed 100% survival when they were treated with 50 mg of ABC per kg (P < 0.0001 versus control group), and only this dosage was able to reduce tissue burden significantly in the five organs studied, i.e., spleen, kidneys, liver, lungs, and brain.Scedosporium prolificans is an emerging filamentous fungus that infects both immunosuppressed and healthy patients, and it is the most common agent of disseminated phaeohyphomycosis (2,11,14,15,20). The infection is probably mostly acquired by inhalation of conidia and can take a wide variety of forms. Disseminated infection is associated mainly with patients with underlying blood malignancies and is usually fatal. The infection is generally treated with amphotericin B (AMB) and occasionally with other drugs, although the outcome is not often successful (2,9,15,20). Several in vitro studies have demonstrated that S. prolificans is generally resistant to the antifungal agents available, and this correlates with the poor clinical response (5, 7). In a previous paper, we demonstrated that high doses of liposomal amphotericin B (10 mg/kg of body weight/day) combined with granulocyte colony-stimulating factor were moderately effective in the treatment of murine scedosporiosis (18). However, further studies are required to determine whether more appropriate dosages of the drug and more suitable strategies that combine it with granulocyte colony-stimulating factor or other lymphokines provide better results. Another alternative, which is practically unexplored, is to use a therapy combining two antifungal agents. In vitro studies have demonstrated that itraconazole combined with terbinafine has a synergic effect against clinical isolates of this fungus (16). This is a line of investigation that deserves to be developed, although the rapid clearance of both drugs in mice makes it necessary to use other animal models for testing this combination. In spite of these promising approaches, alternative treatments for these severe and increasingly frequent mycoses still need to be investigated. The new triazole albaconazole (ABC) showed good in vitro activity against this fungus in a recent study which tested 30 strains (5). This drug has also shown good in vitro activity against dermatophytes, Aspergillus, Paecilomyces, and Candida species, among others (4,8,19). The concentrations of this drug achieved in plasma of mice are very low, and its half-life is short; however, its pharmacokinetics and bioavailability are excellent ...
