Multiple Patterns of Resistance to Fluconazole in Candida glabrata Isolates from a Patient with Oropharyngeal Candidiasis Receiving Head and Neck Radiation

Redding, Spencer W.; Kirkpatrick, William R.; Saville, Stephen; Coco, Brent J.; White, William; Fothergill, Annette; Rinaldi, Michael; Eng, Tony; Patterson, Thomas F.; Lopez-Ribot, Jose

doi:10.1128/jcm.41.2.619-622.2003

Cited by 85Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

Multiple Patterns of Resistance to Fluconazole in Candida glabrata Isolates from a Patient with Oropharyngeal Candidiasis Receiving Head and Neck Radiation

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Redding, Spencer W., Kirkpatrick, William R., Saville, Stephen, Coco, Brent J., White, William, Fothergill, Annette, Rinaldi, Michael, Eng, Tony +2 more·2003·Journal of Clinical Microbiology

DOI 10.1128/jcm.41.2.619-622.2003PMC PMC149712

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Abstract

Candida glabrata has emerged in recent years as a significant cause of systemic fungal infection. We have previously reported on the first three patients receiving radiation for head and neck cancer to develop oropharyngeal candidiasis due to C. glabrata . The goal of this study was to track the development of increased fluconazole resistance in C. glabrata isolates and to evaluate previously described genetic mechanisms associated with this resistance from one of these three patients. The patient was a 52-year-old man with squamous cell carcinoma treated with radiation. At week 7 of his radiation, he developed oropharyngeal candidiasis, which was treated with 200 mg of fluconazole daily for 2 weeks. Serial cultures from this and three subsequent time points yielded C. glabrata . Isolates from these cultures were subjected to antifungal susceptibility testing, DNA karyotyping, and evaluation of the expression of genes previously associated with C. glabrata resistance to fluconazole, CgCDR1 , CgCDR2 , and CgERG11 . Two strains (A and B) of C. glabrata were identified and found to display different patterns of resistance development and gene expression. Strain A developed resistance over a 2-week period and showed no overexpression of these genes. In contrast, strain B first showed resistance 6 weeks after fluconazole therapy was discontinued but showed overexpression of all three genes. In conclusion, development of resistance to fluconazole by C. glabrata is a highly varied process involving multiple molecular mechanisms.

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Fluconazole resistance has been described in a high percentage of patients after extensive use.
“Afterwards, fluconazole resistance has been described in a high percentage of patients [87].”
From CandidaInfections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents (2013) · cites this paper as [87]

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[Molecular mechanisms of fluconazole resistance in clinical isolates of Candida glabrata].
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Authors: Redding, S. W., Kirkpatrick, W. R., Saville, S., Coco, B. J., White, W., Fothergill, A., Rinaldi, M., Eng, T., Patterson, T. F., & Lopez-Ribot, J.
Affiliations: Department of General Dentistry
Department of Medicine, Division of Infectious Diseases
Department of Pathology
The University of Texas at San Antonio Health Science Center (US)
Corresponding author: Redding, Spencer W.
ORCID: White, William
Eng, Tony
Patterson, Thomas F.
Lopez-Ribot, Jose
Venue: Journal of Clinical Microbiology
Publisher: American Society for Microbiology
Published: 2003-02
Volume: 41
Issue: 2
Pages: 619-622
ISSN: 0095-1137 (ISSN-L)
1098-660X
DOI: 10.1128/jcm.41.2.619-622.2003
PMC: PMC149712
OpenAlex: W2147779148
Cited by: 85
References: 23
Citations by year: 2025: 2 · 2024: 1 · 2023: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 6
FWCI: 3.52
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Clinical Microbiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Pfizer
National Institutes of Health (5-R01-)
National Institute of Dental and Craniofacial Research (5-R01-DE11381-6, R01DE011381)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords: Candida glabrata, fluconazole resistance, oropharyngeal candidiasis, head and neck radiotherapy, head and neck cancer, squamous cell carcinoma, multidrug resistance genes, gene overexpression, antifungal susceptibility, serial isolates
MeSH terms: Abnormalities, Radiation-Induced, Antifungal Agents, Candidiasis, Head, Humans, Male, Middle Aged, Neck, Pharyngitis, Fluconazole, Drug Resistance, Fungal, Candida glabrata

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Multiple Patterns of Resistance to Fluconazole in Candida glabrata Isolates from a Patient with Oropharyngeal Candidiasis Receiving Head and Neck Radiation

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