Related Experiment Video

Updated: May 7, 2026

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
08:45

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance

Published on: December 28, 2017

13.9K

Systemic Antifolate Chemotherapy Does Not Select for Fluconazole-Resistant Candida: A Multicenter Clinical Study

Dawid Żyrek1, Joanna Nowicka2, Magdalena Pajączkowska2

  • 1Department of Histology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland.

Pathogens (Basel, Switzerland)
|June 25, 2025
PubMed

Insights

Systemic antifolate therapy with pemetrexed or methotrexate does not increase the risk of fluconazole-resistant yeast colonization or infection in cancer patients. In vitro resistance does not translate to in vivo clinical risk.

Area of Science:

  • Medical Mycology
  • Antifungal Resistance
  • Cancer Therapeutics

Background:

  • Previous in vitro studies show folic acid antagonists like methotrexate can induce multidrug resistance in Candida species to azole antifungals.
  • Antineoplastic antifolates, such as methotrexate and pemetrexed, are used in cancer therapy.
  • The clinical significance of in vitro observed antifungal resistance in vivo remains unclear.

Purpose of the Study:

  • To investigate if systemic antifolate therapy (methotrexate or pemetrexed) is a risk factor for fluconazole-resistant yeast colonization or infection.
  • To evaluate the in vivo impact of antifolate treatment on the development of azole resistance in endogenous yeasts.

Main Methods:

  • A case-control study involving 44 cancer patients receiving high-dose antifolate therapy and 48 controls not exposed to antifolates.
  • Collection of oral swabs and clinical data from all participants.
  • Isolation, identification, and fluconazole susceptibility testing of 109 fungal strains from 13 species.

Main Results:

  • Fluconazole-resistant yeast isolates were found in 9.1% of antifolate-treated patients and 6.3% of control patients.
  • No statistically significant difference in the prevalence of fluconazole-resistant yeasts between the two groups.
  • The study identified 13 different fungal species across all isolates.

Conclusions:

  • Systemic antineoplastic antifolate therapy does not appear to induce azole resistance in endogenous yeast species in vivo.
  • The in vitro phenomenon of antifolate-induced azole cross-resistance does not translate to a clinically significant increased risk of fluconazole-resistant yeast infections in cancer patients.
Keywords:
Candidaantifolatescross-resistancedrug-induced resistancemethotrexatepemetrexedyeast

More Related Videos

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis08:48

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis

Published on: March 19, 2019

7.1K
A Soluble Tetrazolium-Based Reduction Assay to Evaluate the Effect of Antibodies on Candida tropicalis Biofilms06:50

A Soluble Tetrazolium-Based Reduction Assay to Evaluate the Effect of Antibodies on Candida tropicalis Biofilms

Published on: September 16, 2022

3.2K

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Antimicrobial Effectiveness01:28

Antimicrobial Effectiveness

The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...