COMPARISON OF THE ACTIVITY OF FREE AND LIPOSOMAL AMPHOTERICIN-B IN-VITRO AND IN A MODEL OF SYSTEMIC AND LOCALIZED MURINE CANDIDIASIS

Because of the toxicity of amphotericin B-desoxycholate (AmB-d) during systemic therapy, less toxic forms of AmB, which promise to have a br oader therapeutic index, are under investigation. There is, however, n o convincing explanation of how such preparations might be made less t oxic yet retain their antifungal efficacy. In this study, the antifung al activity of a less toxic, unilamellar liposomal (1) preparation of AmB (AmBisome), which is commercially available in some countries, was compared with conventional AmB-d in vitro and in models of systemic a nd localized candidiasis in immunosuppressed mice. Results indicate th at IAmB has four to eight times less antifungal activity than AmB-d in all experimental settings tested. Because IAmB is significantly less active, the therapeutic index of such preparations must be tested clin ically before their use can be recommended solely on the basis of toxi city data.