Further In Vitro Studies with 5-Fluorocytosine

Susceptibilities of 53 isolates of Cryptococcus neoformans and of 15 isolates identified as either Candida albicans or Candida species to 5-fluorocytosine (5-FC) were measured. Thirteen, or 24.5%, of all isolates of C. neoformans were resistant to 5-FC. Eight of these isolates were recovered from patients treated with 100 mg of 5-FC per kg per day, whereas only one was from a patient receiving 150 mg per kg per day. Only one isolate of C. neoformans recovered before treatment was resistant. In 14 cases of cryptococcosis treated with 5-FC at one institution, therapeutic failures associated with resistant isolates of C. neoformans occurred in 6 of 10 cases receiving 100 mg per kg per day but in only one of 4 cases treated with 150 mg per kg per day. Mean concentrations of 5-FC in serum and cerebrospinal fluid were twofold higher in those patients receiving the larger dose. Of 15 isolates of Candida, 5 were susceptible to clinically meaningful concentrations of 5-FC and 8 were totally resistant. Seven of the resistant Candida isolates were isolated before treatment, and selection of resistant isolates during treatment was not observed. Resistant isolates were associated with three of five therapeutic failures. Treatment with 5-FC at 100 mg per kg per day was successful in four of nine patients with systemic candidiasis.