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Effect of Pemetrexed and Methotrexate on Fluconazole Susceptibility in Yeast Cover

Effect of Pemetrexed and Methotrexate on Fluconazole Susceptibility in Yeast

Open Access
|Dec 2025

Figures & Tables

Change of minimum inhibitory concentration (MIC) values for fluconazole among the tested strains of which MIC changed after exposure to methotrexate (MTX) or pemetrexed (PMX)_ ‘The p-value in the first column reflects the outcome of the one-sided Wilcoxon test for paired samples_

Change of minimal inhibitory concentration to Fluconazole [μg/mL] after stimulation with an antifolate
All strains that showed an increase in MICC. albicans strains that showed an increase in MICAll strains that showed a decrease in MICC. albicans strains that showed a decrease in MIC
After MTXMinimal MIC change [%]25%25%-50%-50%
Maximal MIC change [%]1500%1100%-63%-50%
Average MIC change [%]±SD529%± 602%367%± 464%-53%± 6%-50%± 0%
Number of strains7653
p value <0.010.020.030.13*
After PMXMinimal MIC change [%]50%50%-25%-25%
Maximal MIC change [%]700%700%-75%-50%
Average MIC change [%]±SD264%± 251%210%± 277%-50%± 12%-46%± 9%
Number of strains75107
p value <0.010.03<0.01<0.01

Summary characteristics of minimum inhibitory concentration (MIC) values for fluconazole among the tested strains before and after exposure to methotrexate (MTX) or pemetrexed (PMX)_ The p-value in the first column reflects the outcome of the one-sided Wilcoxon test for paired samples_

Minimal inhibitory concentration to Fluconazole [μg/mL]
All strainsn= 18C. albicansn= 12C. tropicalisn= 3N. glabratusn= 3
Before stimulationRange0.13 – 16.000.13 – 1.000.25 – 1.001.00 – 16.00
Median(Q1-Q3)0.25(0.25-0.88)0.25(0.22-0.25)0.50(0.38-0.75)1.00(1.00-8.50)
Geometric mean MIC0.400.240.502.52
After MTXRange0.13 – 16.000.13 – 12.000.25 – 1.000.38 – 16.00
Median(Q1-Q3)0.28(0.25-0.84)0.25(0.13-0.31)0.25(0.25-0.63)16.00(8.19-16.00)
Geometric mean MIC0.550.350.404.58
Average MIC change [%]191%171%-17%479%
Maximal MIC change [%]1500%1100%-50%1500%
p value 0.750.860.16*0.67*
After PMXRange0.13 – 16.000.13 – 8.000.13 – 4.000.25 – 16.00
Median(Q1-Q3)0.19(0.13-0.45)0.16(0.13-0.22)0.25(0.19-2.13)6.00(3.13-11.00)
Geometric mean MIC0.410.240.502.88
Average MIC change [%]75%61%67%142%
Maximal MIC change [%]700%700%300%500%
p value 0.480.440.50*0.67*

Change in the minimum inhibitory concentration (MIC) value for Fluconazole before and after exposure to methotrexate (MTX) or pemetrexed (PMX) for each of the tested strains_ The color of the cell reflects changes in MIC for FLU after antifolate stimulation: red indicates an increase, green a decrease and white-no MIC change_

SpeciesStrain numberMIC before stimulation [μg/mL]MIC after MTX exposure (% of MIC change)MIC after PMX exposure (% of MIC change)
C. albicans10.130.13 (0%)0.19 (50%)
20.250.31 (25%)0.13 (-50%)
30.250.13 (-50%)0.13 (-50%)
41.0012.00 (1100%)8.00 (700%)
50.250.13 (-50%)0.13 (-50%)
60.250.13 (-50%)0.13 (-50%)
70.250.25 (0%)0.19 (-25%)
80.250.25 (0%)0.13 (-50%)
90.252.25 (800%)0.50 (100%)
100.250.31 (25%)0.13 (-50%)
110.130.25 (100%)0.19 (50%)
12 *0.130.31 (150%)0.31 (150%)
C. tropicalis130.500.25 (-50%)0.25 (-50%)
140.250.25 (0%)0.13 (-50%)
151.001.00 (0%)4.00 (300%)
N. glabratus161.0016.00 (1500%)6.00 (500%)
1716.0016.00 (0%)16.00 (0%)
18 **1.000.38 (-63%)0.25 (-75%)
DOI: https://doi.org/10.2478/am-2025-0019 | Journal eISSN: 2545-3149 | Journal ISSN: 0079-4252
Language: English, Polish
Page range: 243 - 250
Submitted on: May 14, 2025
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Accepted on: Nov 24, 2025
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Published on: Dec 23, 2025
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year

© 2025 Dawid Żyrek, Joanna Nowicka, Magdalena Pajączkowska, published by Polish Society of Microbiologists
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.