TABLE 4.
fks hot spot mutations, MICs, and relative increases in MICs compared to modal MICs of rezafungin and comparators for Candida sp. isolates with rezafungin MICs above the wild-type upper limit
| Organism | Mutationa |
MICb (mg/liter) |
Increase in MICc |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Fks1 | Fks2 | RZF | ANF | MCF | AMB | FLU | RZF | ANF | MCF | |
| C. albicans | S645P | NT | 1 | 0.25 | 2 | 0.25 | 0.25 | 4 | 6 | 7 |
| D648Y | NT | 0.5 | 0.06 | 0.125 | 0.25 | 0.125 | 3 | 4 | 3 | |
| P1354S | NT | 0.5 | 0.06 | 0.125 | 0.5 | >64 | 3 | 4 | 3 | |
| P1354S | NT | 0.25 | 0.016 | 0.06 | 0.5 | >32 | 2 | 2 | 2 | |
| P1354S | NT | 0.25 | 0.016 | 0.06 | 0.5 | 64 | 2 | 2 | 2 | |
| P1354S | NT | 0.25 | 0.016 | 0.06 | 0.5 | 64 | 2 | 2 | 2 | |
| P1354P/S | NT | 0.25 | 0.03 | 0.06 | 0.5 | >64 | 2 | 3 | 2 | |
| P1354P/S | NT | 0.25 | 0.06 | 0.06 | 0.5 | >64 | 2 | 4 | 2 | |
| R1361R/S | NT | 0.25 | 0.06 | 0.125 | 0.125 | 0.125 | 2 | 4 | 3 | |
| R1361G | NT | 0.25 | 0.06 | 0.125 | 0.125 | 0.25 | 2 | 4 | 3 | |
| R1361G | NT | 0.25 | 0.016 | 0.06 | 0.5 | 64 | 2 | 2 | 2 | |
| C. glabrata | L630Q | S663F | 2 | 1 | 0.5 | 0.5 | 1 | 4 | 5 | 5 |
| L630Q | S663F | 2 | 1 | 0.5 | 0.5 | 32 | 4 | 5 | 5 | |
| WT | S663F | 2 | 1 | 0.5 | 0.5 | 2 | 4 | 5 | 5 | |
| WT | S663F | 1 | 0.25 | 0.125 | 0.125 | 2 | 3 | 3 | 3 | |
| WT | S663F | 0.5 | 0.25 | 0.125 | 0.5 | 2 | 2 | 3 | 3 | |
| WT | S663F | 0.5 | 0.06 | 0.06 | 0.5 | 2 | 2 | 1 | 2 | |
| WT | S663P | 2 | 1 | 0.5 | 0.125 | 2 | 4 | 5 | 5 | |
| WT | S663P | 0.5 | 0.125 | 0.125 | 0.25 | 4 | 2 | 2 | 3 | |
| Y1429X | Y658N/L664Q | 0.5 | 0.125 | 0.06 | 0.125 | >32 | 2 | 2 | 2 | |
| WT | F659del | 0.5 | 0.06 | 0.06 | 0.25 | >64 | 2 | 1 | 2 | |
| C. tropicalis | F650S | NT | 1 | 0.25 | 1 | 0.25 | 0.5 | 3 | 3 | 5 |
| S654P | NT | 2 | 2 | 2 | 0.5 | 0.5 | 4 | 6 | 6 | |
| C. dubliniensis | S645P | NT | 2 | 0.25 | 2 | 0.03 | 0.125 | 4 | 3 | 6 |
| S645P | NT | 1 | 0.25 | 2 | 0.03 | 0.125 | 3 | 3 | 6 | |
| C. krusei | S659F | NT | 1 | 0.25 | 4 | 0.5 | 32 | 3 | 3 | 7 |
| C. auris | S639F | NT | 16 | 4 | >32 | 1 | >256 | 6 | 6 | >8 |
| S639F | NT | 16 | >32 | >32 | 1 | >256 | 6 | >9 | >8 | |
| S639F | NT | 8 | >32 | >32 | 1 | >256 | 5 | >9 | >8 | |
| S639F | NT | 8 | >32 | >32 | 1 | >256 | 5 | >9 | >8 | |
| S639F | NT | 8 | >32 | >32 | 1 | >256 | 5 | >9 | >8 | |
| S639F | NT | 8 | >32 | >32 | 1 | >256 | 5 | >9 | >8 | |
| S639F | NT | 8 | >32 | >32 | 1 | >256 | 5 | >9 | >8 | |
| S639F | NT | 8 | >32 | >32 | 1 | >256 | 5 | >9 | >8 | |
| WT | NT | 2 | 2 | 0.25 | 1 | >256 | 3 | 5 | 1 | |
| WT | NT | 2 | 1 | 0.25 | 1 | 256 | 3 | 4 | 1 | |
| WT | NT | 2 | 0.03 | 0.03 | 0.5 | 256 | 3 | −1 | −2 | |
a
NT, not tested.
b
MICs above the wild-type upper limit/ECOFF are in boldface. RZF, rezafungin; ANF, anidulafungin; MCF, micafungin; AMB, amphotericin B; FLU, fluconazole.
c
The number of two-fold dilution increases in the MIC compared to the modal MIC.