TABLE 3.
Checkerboard assays of fluconazole-resistant C. albicans clinical isolates overexpressing the multidrug efflux pumps CDR1, CDR2, and MDR1 and/or overexpressing the drug target ERG11 as indicateda
| Strain and compound | Compound concn (μg/ml) |
FLC concn (μg/ml) |
FICI | Outcome | ||||
|---|---|---|---|---|---|---|---|---|
| MIC1* | MIC2* | FIC | MIC1 | MIC2 | FIC | |||
| 95-142 (CDR1/CDR2) | ||||||||
| 1 | 69 | 0.13 | 0.002 | 64 | 16 | 0.25 | 0.25 | Synergy |
| 2 | 70 | 0.55 | 0.008 | 64 | 16 | 0.25 | 0.26 | Synergy |
| 3 | 73 | 0.14 | 0.002 | 64 | 16 | 0.25 | 0.25 | Synergy |
| 4 | 76 | 0.29 | 0.004 | 64 | 16 | 0.25 | 0.25 | Synergy |
| 96-25 (MDR1/ERG11) | ||||||||
| 1 | 69 | 0.13 | 0.002 | 32 | 2 | 0.06 | 0.06 | Synergy |
| 2 | 70 | 0.14 | 0.002 | 32 | 8 | 0.25 | 0.25 | Synergy |
| 3 | 36 | 0.14 | 0.004 | 32 | 2 | 0.06 | 0.06 | Synergy |
| 4 | 38 | 0.15 | 0.004 | 32 | 2 | 0.06 | 0.06 | Synergy |
| 5 | 80 | 80 | 1 | 32 | 32 | 1 | 2 | Indifferent |
| 12-99 (all four genes) | ||||||||
| 1 | 69 | 0.13 | 0.002 | 128 | 32 | 0.25 | 0.25 | Synergy |
| 2 | 70 | 0.14 | 0.002 | 128 | 32 | 0.25 | 0.25 | Synergy |
MIC values were determined by a broth microdilution assay according to CLSI protocol M27-A3 (2008) using 50% growth reduction as the cutoff for the reported MIC values. MIC1, the MIC of the compound or FLC alone; MIC2, the MIC of the compound or FLC in the presence of FLC or compound, respectively. FIC, fractional inhibitory concentration; FICI, fractional inhibitory concentration index. *, values were converted from μM to μg/ml.