Table 2.
Effect of ospemifene-itraconazole (ITC) combination against different fungal strains.
| Fungal Strains | MIC (µg/ml) | ΣFICIa | Interaction | |||
|---|---|---|---|---|---|---|
| ITC* | Ospemifene | |||||
| Alone | Combined | Alone | Combined | |||
| C. albicans SC5314 | 0.125 | 0.0312 | >256 | 2 | 0.26 | SYN |
| C. albicans NR-29448 | 4* | 0.0625 | 8 | 0.05 | SYN | |
| C. albicans NR-29437 | 0.5 | 0.06 | 4 | 0.14 | SYN | |
| C. albicans ATCC MYA-573 | 0.5 | 0.25 | 1 | 0.50 | SYN | |
| C. albicans TWO7241 | 0.5 | 0.125 | 0.5 | 0.25 | SYN | |
| C. albicans TWO7243 | 1* | 0.5 | 1 | 0.50 | SYN | |
| C. albicans SC-TAC1G980E | 0.5 | 0.25 | 1 | 0.50 | SYN | |
| C. albicans SC-MRR1P683S | 0.25 | 0.062 | 4 | 0.26 | SYN | |
| C. glabrata ATCC 66032 | 0.5 | 0.5 | 4 | 1.02 | IND | |
| C. glabrata ATCC MYA-2950 | 0.5 | 0.5 | 4 | 1.02 | IND | |
| C. glabrata ATCC 2001 | 0.5 | 0.5 | 4 | 1.02 | IND | |
| C. glabrata HM-1123 | 0.5 | 0.5 | 4 | 1.02 | IND | |
| C. auris 385 | 1* | 0.25 | 4 | 0.27 | SYN | |
| C. auris 386 | 0.5 | 0.125 | 4 | 0.27 | SYN | |
| C. auris 388 | 1* | 0.25 | 4 | 0.27 | SYN | |
| C. auris 389 | 1* | 0.25 | 4 | 0.27 | SYN | |
| C. auris 390 | 1* | 0.125 | 4 | 0.14 | SYN | |
| C. neoformans NR-41291 | 0.25 | 0.062 | 4 | 0.26 | SYN | |
| C. neoformans NR-41295 | 0.5 | 0.25 | 1 | 0.50 | SYN | |
| C. neoformans NR-41298 | 0.5 | 0.125 | 2 | 0.26 | SYN | |
| A. fumigatus NR-35304 | 0.5 | 0.25 | 0.5 | 0.50 | SYN | |
| A. fumigatus NR-35312 | 0.5 | 0.25 | 2 | 0.50 | SYN | |
| A. fumigatus NR-35302 | 0.5 | 0.25 | 1 | 0.50 | SYN | |
aΣFICI (fractional inhibitory concentration index) values, rounded to the nearest two decimal places, were used to measure the interaction between the tested combinations. ΣFICI interpretation corresponded to the following definitions: synergistic (SYN), ΣFICI ≤ 0.50; additive (ADD), ΣFICI > 0.50 and ≤1; and indifference (IND), ΣFICI > 1 and ≤ 4.
*Indicates itraconazole resistance. MIC values of ≥ 1 µg/ml and > 2 µg/ml were selected as tentative itraconazole resistance breakpoints against yeast-like pathogens and molds, respectively52,53.