COMPARISON OF LIPOSOMAL AMPHOTERICIN-B TO AMPHOTERICIN-B FOR TREATMENT OF MURINE CRYPTOCOCCAL MENINGITIS

Objective: The efficacy of liposomal amphotericin B (AmBisome(R)), a unilamellar amphotericin B liposomal preparation, was compared to that of conventional amphotericin B (Fungizone(R)), in treatment of murine cryptococcal meningitis. Materials and Methods: Meningitis was induced in outbred ICR mice by intracerebral infection with a clinical isolate of Cryptococcus neoformans. Therapy was administered days 2, 3, 5, 7, 8, 12, 15 post challenge. Protection was measured as prolonged survival and reduction of brain tissue counts. Results: Amphotericin B deoxycholate at 0.3 mg/kg and liposomal amphotericin B at 1.0 mg/kg showed comparable and significant protection over controls, with no difference between groups. Liposomal amphotericin B was nontoxic through the entire range of doses tested (0.3-30 mg/kg). Administration of seven doses, at 30 mg/kg, resulted in negative brain cultures in 78 % of animals day 30 post challenge. Conclusion: While not as potent amphotericin B deoxycholate at doses less than or equal to 1.0 mg/kg, liposomal amphotericin B was effective in treating murine cryptococcal meningitis and can be administered in sufficiently high doses to produce negative cultures in the majority of infected animals. These results suggest liposomal amphotericin B will be a useful alternative in cryptococcal meningitis.