Candida albicans resistance to 5-fluorocytosine: frequency of partially resistant strains among clinical isolates.

Resistance to 5-fluorocytosine was studied in 137 independent Candida albicans clinical isolates. Seventy-eight isolates (57%) were susceptible; 51 isolates (37%) were partially resistant; 8 isolates (6%) were highly resistant. All partially resistant isolates gave rise to variants which were highly resistant. Some susceptible isolates gave rise to variants which were highly resistant; two such isolates were shown to be heterozygous for resistance, and these isolates define a new type of heterozygote. A partially resistant isolate gave rise to resistant variants which were auxotrophic for lysine; this result was interpreted as preliminary evidence that the allele which determined resistance was linked to an allele which determined auxotrophy for lysine. It is suggested that heterozygotes constitute a source of preexisting mutant alleles which determine resistance, and that 5-fluorocytosine treatment of infections due to heterozygotes may result in significant selection for resistant variants. A simple screening procedure is described by which partially resistant strains may be recognized.