In vivo and in vitro antifungal activity of the polyene derivative SPA-S-753 against encapsulated form of Cryptococcus neoformans

The in vitro and in vivo activity of SPA-S-753 (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diaspartate), a new water soluble polyene, was compared with amphotericin B against Cryptococcus neoformans in encapsulated (K) and nonencapsulated (N) morphological forms. In vitro tests against 17 isolates of C. neoformans (in K or N form) showed that SPA-S-753 activity is about ten times higher than that of amphotericin B. In direct contact tests the SPA-S-753 cytocidal action was significantly higher than that of amphotericin B; the K cells are, however, less sensitive to the cytocidal action exerted by the two polyenes even when using concentrations 4-fold higher than those used against the N cells and they present a smaller potassium ion release. The cytocidal activity of the two polyenes is favoured by a low electrolyte concentration and an acid pH. SPA-S-753 microbicidal activity by contact in vivo, in mice infected with C. neoformans N cells by i.p. route, is more powerful than that of amphotericin B. In protection tests in mice infected with 10 LD(50) of C. neoformans K cells, SPA-S-753 action is again more powerful, but not to a significant degree, than that of amphotericin B, In conclusion, both substances showed a reduced in vitro and in vivo activity against C. neoformans in the K morphological form. Nevertheless our results demonstrate that SPA-S-753 exerts an antifungal over-all activity that is more effective than that of amphotericin B under similar experimental conditions.