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The antimycotic activity of 5-fluorocytosine
  1. R. J. Holt,
  2. R. L. Newman1
  1. Queen Mary's Hospital for Children, Carshalton, Surrey

    Abstract

    5-Fluorocytosine (5 FC) showed marked in vitro activity against nearly all the clinical isolates of Candida and Cryptococcus examined; the required minimal inhibitory concentration was usually below 2 μg/ml and the minimal cidal concentration below 10 μg/ml. The drug had limited activity towards Aspergillus species and dermatophytes. Strains of Candida and other fungi with greatly enhanced resistance were fairly readily obtained by successive cultures on increasingly high concentrations of 5-fluorocytosine.

    Serum, urine, and faecal assays of 5 FC were made by a microbiological method on specimens from eight children who received between 100 and 25 mg/kg/day of the drug over several weeks for candidosis of the urinary tract usually associated with congenital anatomical abnormalities. Seven of these cases were successfully treated but in the other the Candida became highly resistant and treatment was discontinued. Serum drug levels ranged up to 30 μg/ml; urine levels were frequently between 200 and 500 μg/ml. No 5 FC was detected in faecal samples.

    Sensitivity tests and assays were also made on samples from subjects receiving 5 FC in other hospitals; five had systemic C. albicans infection, the sixth had cryptococcal meningitis. In the latter case levels up to 34 μg/ml were recorded in the cerebrospinal fluid after oral administration, and an investigation was made into the possibility of competitive antagonism by intrathecal cytosine arabinoside given for Hodgkin's disease. The emergence in two other cases of strains of Candida highly resistant to 5 FC is discussed, and it is suggested that careful laboratory monitoring of cases receiving 5 FC must continue throughout therapy and afterwards.

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    Footnotes

    • 1 Dr Newman died after this paper had been written.