Table 1.
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 strains n= 18 | C. albicans n= 12 | C. tropicalis n= 3 | N. glabratus n= 3 | ||
| Before stimulation | Range | 0.13 – 16.00 | 0.13 – 1.00 | 0.25 – 1.00 | 1.00 – 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 MIC | 0.40 | 0.24 | 0.50 | 2.52 | |
| After MTX | Range | 0.13 – 16.00 | 0.13 – 12.00 | 0.25 – 1.00 | 0.38 – 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 MIC | 0.55 | 0.35 | 0.40 | 4.58 | |
| Average MIC change [%] | 191% | 171% | -17% | 479% | |
| Maximal MIC change [%] | 1500% | 1100% | -50% | 1500% | |
| p value | 0.75 | 0.86 | 0.16* | 0.67* | |
| After PMX | Range | 0.13 – 16.00 | 0.13 – 8.00 | 0.13 – 4.00 | 0.25 – 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 MIC | 0.41 | 0.24 | 0.50 | 2.88 | |
| Average MIC change [%] | 75% | 61% | 67% | 142% | |
| Maximal MIC change [%] | 700% | 700% | 300% | 500% | |
| p value | 0.48 | 0.44 | 0.50* | 0.67* | |
Table 2.
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.
| Species | Strain number | MIC before stimulation [μg/mL] | MIC after MTX exposure (% of MIC change) | MIC after PMX exposure (% of MIC change) |
|---|---|---|---|---|
| C. albicans | 1 | 0.13 | 0.13 (0%) | 0.19 (50%) |
| 2 | 0.25 | 0.31 (25%) | 0.13 (-50%) | |
| 3 | 0.25 | 0.13 (-50%) | 0.13 (-50%) | |
| 4 | 1.00 | 12.00 (1100%) | 8.00 (700%) | |
| 5 | 0.25 | 0.13 (-50%) | 0.13 (-50%) | |
| 6 | 0.25 | 0.13 (-50%) | 0.13 (-50%) | |
| 7 | 0.25 | 0.25 (0%) | 0.19 (-25%) | |
| 8 | 0.25 | 0.25 (0%) | 0.13 (-50%) | |
| 9 | 0.25 | 2.25 (800%) | 0.50 (100%) | |
| 10 | 0.25 | 0.31 (25%) | 0.13 (-50%) | |
| 11 | 0.13 | 0.25 (100%) | 0.19 (50%) | |
| 12 * | 0.13 | 0.31 (150%) | 0.31 (150%) | |
| C. tropicalis | 13 | 0.50 | 0.25 (-50%) | 0.25 (-50%) |
| 14 | 0.25 | 0.25 (0%) | 0.13 (-50%) | |
| 15 | 1.00 | 1.00 (0%) | 4.00 (300%) | |
| N. glabratus | 16 | 1.00 | 16.00 (1500%) | 6.00 (500%) |
| 17 | 16.00 | 16.00 (0%) | 16.00 (0%) | |
| 18 ** | 1.00 | 0.38 (-63%) | 0.25 (-75%) |
Table 3.
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 MIC | C. albicans strains that showed an increase in MIC | All strains that showed a decrease in MIC | C. albicans strains that showed a decrease in MIC | ||
| After MTX | Minimal MIC change [%] | 25% | 25% | -50% | -50% |
| Maximal MIC change [%] | 1500% | 1100% | -63% | -50% | |
| Average MIC change [%] ±SD | 529% ± 602% | 367% ± 464% | -53% ± 6% | -50% ± 0% | |
| Number of strains | 7 | 6 | 5 | 3 | |
| p value | <0.01 | 0.02 | 0.03 | 0.13* | |
| After PMX | Minimal MIC change [%] | 50% | 50% | -25% | -25% |
| Maximal MIC change [%] | 700% | 700% | -75% | -50% | |
| Average MIC change [%] ±SD | 264% ± 251% | 210% ± 277% | -50% ± 12% | -46% ± 9% | |
| Number of strains | 7 | 5 | 10 | 7 | |
| p value | <0.01 | 0.03 | <0.01 | <0.01 | |