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Cited by 232Antifungal resistance and susceptibilityFungal Infections and StudiesFungal Plant Pathogen Control

Evolving Role of Flucytosine in Immunocompromised Patients: New Insights into Safety, Pharmacokinetics, and Antifungal Therapy

Francis, P., Walsh, T. J.·1992·Clinical Infectious Diseases
DOI 10.1093/clind/15.6.1003
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Abstract

Flucytosine is an antifungal agent useful in combination with amphotericin B in the treatment of several deeply invasive mycoses. The potentially dose-limiting, hematologic, gastrointestinal, and hepatic toxicities of flucytosine lead to a reluctance to use it in myelosuppressed patients. To investigate the safety and tolerability of flucytosine in this setting, we evaluated its use in 17 patients with cancer or aplastic anemia during a 2 1/2-year period at our institution and reviewed the literature describing mechanisms of action, resistance, in vitro and in vivo antifungal activity, clinical antifungal activity, pharmacokinetics, and toxicity. The combination of amphotericin B plus flucytosine eradicated the mycosis in 12 (71%) of 17 patients, whereas 3 (18%) of 17 died of progressive fungal infection. Serial serum levels of flucytosine measured by a creatinine iminohydrolase assay permitted reliable dosage adjustment. During therapy, only 2 (12%) of 17 patients had elevated mean serum levels of flucytosine (> 100 micrograms/mL) and 3 (18%) other patients had transiently elevated levels. Paired serum samples (n = 45) obtained at steady state during therapy with orally administered flucytosine showed similar peak and trough levels. Adverse effects of flucytosine therapy included one case each of reversible nausea, diarrhea, elevated transaminase levels, and thrombocytopenia. No cases of bone marrow aplasia, enterocolitis, hepatitis, or death due to flucytosine toxicity were…

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Crossref · 10.1093/clind/15.6.1003

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  • Emergence of resistance may occur rapidly when flucytosine is used as a single agent.

    “emergence of resistance may occur rapidly when this compound is used as a single agent [173].”

    From Guidelines for Treatment of Candidiasis (2004) · cites this paper as [173]

  • All of these triazole agents have the same mechanism of action against Candida and, in many instances, are affected by the same resistance mechanisms.

    “All of these agents have the same mechanism of action against Candida and, in many instances, are affected by the same resistance mechanisms (24, 32, 81, 225, 226, 260, 274, 294, 312).”

    From Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem (2007) · cites this paper as [81]

  • Voriconazole binds much more effectively to the cytochrome P-450 isoenzyme target in C. krusei than does fluconazole.

    “because voriconazole binds much more effectively to the cytochrome P-450 isoenzyme target in C. krusei than does fluconazole (81, 274).”

    From Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem (2007) · cites this paper as [81]

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Authors
Francis, P., & Walsh, T. J.
Affiliations
National Institutes of Health (US)
Corresponding author
Walsh, T. J.
ORCID
Walsh, T. J.
Venue
Clinical Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
1992-12-01
Volume
15
Issue
6
Pages
1003-1018
ISSN
  • 1058-4838 (ISSN-L)
  • 1537-6591
DOI
10.1093/clind/15.6.1003
OpenAlex
W1968406074
Cited by
232
References
92
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 4 · 2017: 3 · 2016: 4 · 2015: 9 · 2014: 6 · 2013: 3 · 2012: 10
FWCI
5.81
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords
5-fluorocytosine, amphotericin B, invasive fungal infections, immunocompromised patients, myelosuppression, pharmacokinetics, drug toxicity, serum drug concentration monitoring, combination antifungal therapy, aplastic anemia, cancer patients, antifungal resistance
MeSH terms
Adolescent, Adult, Amphotericin B, Child, Preschool, Drug Therapy, Combination, Female, Flucytosine, Humans, Male, Middle Aged, Mycoses, Immunocompromised Host

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