J. Utz
1975
Citations
0
Influential Citations
6
Citations
Journal
Bulletin of the New York Academy of Medicine
Abstract
Chemistry. Flucytosine (5-fluorocytosine or 5-FC) is a fluorinated pyrimidine. It is a white crystalline powder with a molecular weight of 129.1; it is slightly soluble in water and readily soluble in alcohol (Figure i ). Mode of action. Flucytosine is incorporated by some yeasts and then interferes with subsequent pyrimidine metabolism at one or perhaps several enzymatic sites. Flucytosine enters the cell via permease enzymes located on the surface. Within the cell it is deaminated by cytosine deaminase to fluorouracil. Uracil is used preferentially by fungi and represses the internal synthesis of pyrimidines. Thus, flucytosine ultimately would seem to interfere with thymidylate synthetase. Susceptibility. Only a few genera of fungi are susceptible: Cryptococcus neoformans, Candida sp., Torulopsis sp., and Cladosporium sp. Even within these genera, however, there are marked differences among isolates-notably with Candida sp., of which 50% of isolates may be resistant de novo. C. neoformans isolates are generally more sensitive, and the minimal inhibitory concentration (MIC) ranges from 0.39 to 12.5 Mug./ml. The minimal fungicidal concentration (MFC) usually does not vary by more than one tube, although occasional exceptions show a marked discrepancy. In in zivo studies-customarily performed in mice-with isolates of