An in vitro study on the active conversion of flucytosine to fluorouracil by microorganisms in the human intestinal microflora

Background: Investigation of the rate of active conversion of flucytosine to fluorouracil by microorganisms in the intestinal microflora. Methods: Active conversion of flucytosine was investigated using viable and nonviable Escherichia coli at different flucytosine concentrations. Additionally, flucytosine conversion was studied in fecal specimens from 3 neutropenic patients at the start of the antimicrobial/antifungal prophylaxis (C/A regimen) and 1 week later. Results: Flucytosine levels decreased by an average of 72, 71 and 72% flucytosine after incubation for 48 h of 1010 viable E. coli/ml suspension in broth containing 13, 130 and 1,300 mg/l flucytosine, respectively. The decreasing flucytosine levels corresponded approximately to an identical increase in fluorouracil levels. Also, a 44% decrease of flucytosine levels occurred when nonviable E. coliwere used, indicating that bacterial viability is not necessary for this conversion. When fecal specimens of 2 patients were investigated prior to the C/A regimen, significant flucytosine conversion occurred, whereas this conversion was not observed in the corresponding fecal specimens after 1 week of C/A regimen. Conclusion: These in vitro experiments showed that extensive flucytosine conversion can occur in the human intestinal microflora by E. coli. Consequently, fluorouracil exposure and fluorouracil-related toxicity may occur in the flucytosine-treated patient. Copyright

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