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Cited by 139Fungal Infections and StudiesAntifungal resistance and susceptibilityFungal Plant Pathogen Control

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

Heteroresistance to Fluconazole and Voriconazole in Cryptococcus neoformans

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Mondon, P., Petter, R., Amalfitano, G., Luzzati, R., Concia, E., Polacheck, I., Kwon-Chung, K. J.·1999·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.43.8.1856PMC PMC89380
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Abstract

Cryptococcus neoformans isolates that exhibited unusual patterns of resistance to fluconazole and voriconazole were isolated from seven isolates from two different geographical regions: one isolate from an Israeli non-AIDS patient and six serial isolates from an Italian AIDS patient who had suffered six recurrent episodes of cryptococcal meningitis. Each isolate produced cultures with heterogeneous compositions in which most of the cells were susceptible, but cells highly resistant to fluconazole (MICs, ≥64 μg/ml) were recovered at a variable frequency (7 × 10 −3 to 4.6 × 10 −2 ). Evidence showed that this type of resistance is innate and is unrelated to drug exposure since the Israeli patient had never been treated with azoles or any other antimycotic agents. Analysis of clonal subpopulations of these two strains showed that they exhibited heterogeneous patterns of resistance. The number of subpopulations which grew on fluconazole or voriconazole agar declined progressively with increasing azole concentration without a sharp cutoff point. For the Italian serial isolates, the number of clonal populations resistant to fluconazole (64 μg/ml) and voriconazole (1 μg/ml) increased steadily, yielding the highest number for the isolate from the last episode. Attempts to purify a sensitive subpopulation failed, but clones highly resistant to fluconazole (100 μg/ml) and moderately resistant to voriconazole (1 μg/ml) always produced a homogeneous population of resistant cells. Upon maintenance on drug-free medium, however, the majority of the homogeneously resistant cells of these subclones lost their resistance and returned to the stable initial heteroresistant phenotype. The pattern of heteroresistance was not affected by the pH or osmolarity of the medium but was influenced by temperature. The resistance appeared to be suppressed at 35°C and was completely abolished at 40°C. Although heterogeneity in azole resistance among subpopulations of single isolates has been reported for Candida species, the transient changes in expression of resistance under different growth conditions reported here have not been observed in fungal pathogens.

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Metadata

Authors
Mondon, P., Petter, R., Amalfitano, G., Luzzati, R., Concia, E., Polacheck, I., & Kwon-Chung, K. J.
Affiliations
  • National Institutes of Health (US)
  • University of Verona (IT)
  • Hadassah Medical Center (IL)
ORCID
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
1999-08
Volume
43
Issue
8
Pages
1856-1861
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.43.8.1856
PMC
PMC89380
OpenAlex
W2000804360
Cited by
139
References
36
Citations by year
2026: 5 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 11 · 2021: 5 · 2020: 9 · 2019: 7 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 2 · 2014: 10 · 2013: 7 · 2012: 12
FWCI
3.27
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
Funders
Pfizer
Topics
  • Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
Keywords
Cryptococcus neoformans, azole resistance, fluconazole, voriconazole, heteroresistance, clonal subpopulations, cryptococcal meningitis, AIDS, temperature-dependent resistance, loss of resistance, serial isolates
MeSH terms
Acquired Immunodeficiency Syndrome, Adult, Amphotericin B, Antifungal Agents, Cryptococcus neoformans, Drug Resistance, Microbial, Humans, Hydrogen-Ion Concentration, Male, Microbial Sensitivity Tests, Osmolar Concentration, Phenotype, Pyrimidines, Staining and Labeling, Temperature, Triazoles, Fluconazole, Meningitis, Fungal, Itraconazole, Voriconazole

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