LIPOSOMAL AMPHOTERICIN-B (AMBISOME) REDUCES DISSEMINATION OF INFECTION AS COMPARED WITH AMPHOTERICIN-B DEOXYCHOLATE (FUNGIZONE) IN A RAT MODEL OF PULMONARY ASPERGILLOSIS

The efficacy of AmBisome, a liposomal formulation of amphotericin B, w as compared with that of Fungizone (amphotericin B desoxycholate), in a rat model of unilateral, pulmonary aspergillosis. Repeated administr ation of cyclophosphamide resulted in persistent, severe, granulocytop enia. The left lung was inoculated with a conidial suspension of Asper gillus fumigatus, thus establishing an unilateral infection. Antifunga l treatment was started 40 h after fungal inoculation, at which time m ycelial disease was confirmed by histological examination. Both Fungiz one 1 mg/kg and AmBisome 10 mg/kg resulted in increased survival in te rms of delayed as well as reduced mortality. Quantitative cultures of lung tissue showed that only AmBisome 10 mg/kg resulted in reduction o f the number of fungal cfus in the inoculated left lung. Compared with Fungizone, both AmBisome 1 mg/kg/day and AmBisome 10 mg/kg/day signif icantly prevented dissemination from the infected left lung to the rig ht lung. In addition, both AmBisome regimens reduced hepatosplenic dis semination, and the 10 m/kg dosage fully prevented this complication. In conclusion, when compared with Fungizone, in this model AmBisome is more effective in reducing dissemination of unilateral, pulmonary asp ergillosis, even when given in relatively low dosage. Such low dosages may have a place in prophylactic settings.