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Flucytosine: Site of Action, Mechanism of Resistance and Use in Combination Therapy

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Antimicrobial Drug Resistance

Part of the book series: Infectious Disease ((ID))

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A fl uorinated pyrimidine, 5-fl ucytosine (fl uorocytosine; 5-FC, Fig. 1), was initially developed as a potential anti-cancer agent but it was not suffi ciently effective in the fi eld of cancer chemotherapy (1). Later, 5-FC proved to be active in experimental candidiasis and cryptococcosis in mice (2) and was used to treat human infections (3). In addition to its activity against Candida and Cryptococcus, 5-FC also has an inhibitory activity against fungi causing chromoblastomycosis (4); however, it is ineffective against infections caused by fi lamentous fungi. 5-FC has a high prevalence of primary resistance in many fungal species. Due to this primary resistance, 5-FC is used mainly in combination with other antifungals (primarily amphotericin B, AmB) and more recently it has been investigated in combination with other agents including fl uconazole (FLU), ketoconazole (KTZ), itraconazole (ITRA), voriconazole (VORI) and echinocandins (e.g., micafungin, MICA and caspofungin, CAS). It is used only rarely as a single agent.

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Authors and Affiliations

  1. Research Associate, Center for Medical Mycology and Mycology Reference Laboratory, Department of Dermatology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH, USA

    Jyotsna Chandra

  2. Postdoctoral Fellow, Center for Medical Mycology and Mycology Reference Laboratory, Department of Dermatology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH, USA

    Sotohy Mohammad

  3. Center for Medical Mycology, Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH, USA

    Mahmoud A. Ghannoum

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  1. Jyotsna Chandra
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  1. Executive Vice President & Chief Medical Offi cer, Idenix Pharmaceuticals, Cambridge, MA, USA

    Douglas L. Mayers MD

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Chandra, J., Mohammad, S., Ghannoum, M.A. (2009). Flucytosine: Site of Action, Mechanism of Resistance and Use in Combination Therapy. In: Mayers, D.L. (eds) Antimicrobial Drug Resistance. Infectious Disease. Humana Press. https://doi.org/10.1007/978-1-59745-180-2_27

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