Chromoblastomycosis, flucytosine

The spectrum of activity of flucytosine is restricted to C neoformans, some Candida species, and the dematiaceous molds that cause chromoblastomycosis. Flucytosine is not used as a single agent because of its demonstrated synergy with other agents and to avoid the development of secondary resistance. Clinical use at present is confined to combination therapy, either with amphotericin for... 

Flucytosine Interferes with DNA and RNA synthesis selectively in fungi Synergistic with amphotericin systemic toxicity in host due to DNA and RNA effects Cryptococcus and chromoblastomycosis infections Oral duration, hours renal excretion Toxicity Myelosuppression... 

Antifungal spectrum Flucytosine is fungistatic and effective in treating chromoblastomycosis and in combination for candidiasis, and cryptococcosis. 

Resistance Resistance can develop during therapy and is the reason that flucytosine is not used as a single antimycotic drug except for chromoblastomycosis. The rate of emergence of resistant fungal cells is lower with the combination of amphotericin B and flucytosine than it is with flucytosine alone. Decreased levels of any of the enzymes in the conversion of 5-FC to 5-FU and beyond, or increased synthesis of cytosine, can confer resistance. 

Flucytosine (ancobon) is clinically useful for Cryptococcus neoformans, Candida spp., and chromoblastomycosis. It is given orally at 100 mgAg/day, in divided doses at 6-hour intervals and is used predominantly in combination with amphotericin B. An all-oral regimen of flucytosine plus fluconazole has been advocated for therapy of AIDS patients with cryptococcosis, but the combination has substantial Gl toxicity without evidence that flucytosine improves the outcome. The combination of flucytosine with C-AMB runs the risk of substantial bone marrow suppression or colitis if the flucytosine dose is not promptly adjusted downward if amphotericin B—induced azotemia occurs. It is common practice in HIV-negative patients with cryptococcal meningitis to begin with C-AMB or ambisome plus flucytosine and change to fluconazole after the patient has improved. 

The major towback of Flucytosine is rapid development of resistance in fungi, either by mutations or by increased synthesis of pyrimidines this limits the use of 9 as a single antifungal agent. Monotherapy with Flucytosine is currently only used in some cases of chromoblastomycosis and in uncomplicated candidosis in all other cases, 9 is used together with other agents, usually Amphotericin B [173]. 

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