amphotericin-b and sordarin

In vitro susceptibility to the sordarin derivative GM 237354 and amphotericin B were tested in a total of 190 Cryptococcus neoformans clinical isolates from different geographical areas of Spain and South American countries. Minimal inhibitory concentrations (MICs) were obtained using the NCCLS reference microbroth dilution method and analysed according the serotypes of Cr. neoformans. The MICs for amphotericin B were lower than 1.0 microg ml(-1) (MIC90% 0.5 microg ml(-1) , MIC50% 0.125 microg ml(-1)) but five isolates showed MICs of 2.0 microg ml(-1) to GM 237354 (MIC90% 1.0 microg ml(-1), MIC50% 0.5 microg ml(-1)). Cryptococcus neoformans var. gattii serotype B, was significantly less susceptible than A and AD serotypes (P = 0.047 and P = 0.022, respectively).

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Humans; Indenes; Microbial Sensitivity Tests; Serotyping

Sordarins are new antifungals which inhibit fungal protein synthesis by blocking elongation factor 2. Three compounds were evaluated in a murine model of histoplasmosis. Immune-competent mice were infected intravenously with 10(6) to 10(8) CFU of Histoplasma capsulatum yeast cells. Mice were treated either orally with sordarins or fluconazole from day 2 through 8 after infection or intraperitoneally with amphotericin B during the same period. Protection was measured by increased rates of survival for 30 days after infection or reduction of lung or kidney tissue counts 9 days after infection. All three of the antifungal drugs tested were protective compared with controls. Sordarins were effective at doses as low as 2 mg/kg of body weight/day. This novel class of drugs compared favorably with amphotericin B and fluconazole for the treatment of histoplasmosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Fluconazole; Histoplasma; Histoplasmosis; Indenes; Kidney; Lung; Male; Mice; Mice, Inbred ICR