In vitro susceptibility of the opportunistic fungus Cryptococcus neoformans to anthelmintic benzimidazoles.
Ten benzimidazole derivatives and amphotericin B were tested in vitro against three isolates of Cryptococcus neoformans. Drug concentrations inhibiting 50% of growth (IC50s) were determined. Four derivatives, including mebendazole and albendazole, had moderately high activities (IC50 = 0.1 to 0.3 microgram/ml). Fenbendazole, however, was 10-fold more active (IC50 = 0.01 to 0.02 microgram/ml) and also 2-fold more active than amphotericin B. Ten additional clinical isolates of C. neoformans were tested against fenbendazole, mebendazole, and albendazole; similar susceptibilities were observed. Drug concentrations lethal to 90% of the cells (LC90s) were determined for two isolates. The LC90s of albendazole and mebendazole were 0.92 to 2.1 micrograms/ml, and those of fenbendazole were 0.06 to 0.07 microgram/ml; the latter are eight to ninefold lower than the LC90s of amphotericin B that were obtained. Spontaneously arising mutants displaying partial resistance to fenbendazole arose at a low frequency (5 x 10(-9).
Cruz
M C
MC
Medical College of Pennsylvania, Philadelphia 19129.
Bartlett
M S
MS
Edlind
T D
TD
D000666:Amphotericin B / Q000494:pharmacology; D000871:Anthelmintics / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D012441:Saccharomyces cerevisiae / Q000187:drug effects
D000871:Anthelmintics; D000935:Antifungal Agents; D001562:Benzimidazoles; D000666:Amphotericin B