Flucytosine: Site of Action, Mechanism of Resistance and Use in Combination Therapy
Abstract
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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Flucytosine is the only pyrimidine analog with antimycotic properties currently in use for human treatment, and it can convert into 5-fluorouracyl and further into 5-fluorodeoxyuridine inside the fungal cell.
“The only pyrimidine analog with antimycotic properties currently in use for human treatment is flucytosine, which has the potential to convert into 5-fluorouracyl and further to 5-fluorodeoxyuridine inside the fungal cell [27].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [27]
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- Authors
- Chandra, J., Mohammad, S., & Ghannoum, M. A.
- Affiliations
- University Hospitals of Cleveland (US)
- Corresponding author
- Ghannoum, Mahmoud A.
- Venue
- Antimicrobial Drug Resistance
- Publisher
- Humana Press
- Published
- 2009
- Pages
- 313-326
- OpenAlex
- W1914885837
- Cited by
- 6
- References
- 96
- Citations by year
- 2024: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2013: 1
- FWCI
- 0.00
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- Locations
- Humana Press eBooks (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- 5-fluorocytosine, antifungal agents, mechanism of action, primary drug resistance, combination antifungal therapy, candidiasis, cryptococcosis, chromoblastomycosis, amphotericin B, echinocandins, azoles, site of action
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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