TABLE 2.
Synergistic in vitro activities of L-685,818 combined with bafilomycin A1, fluconazole, LiCl, and MK-0991/caspofungin acetate against serotype A C. neoformans wild-type strain H99 and calcineurin (Δcna1) and FKBP12 (Δfrr1) mutant strains at 30°C
| Strain type | MIC (μg/ml) ofa:
|
FIC index
|
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Agent alone
|
Agents combined
|
||||||||||||
| L6 | BF | FL | Li | MK | L6+BF | L6+FL | L6+Li | L6+MK | L6+BF | L6+FL | L6+Li | L6+MK | |
| H99 | >25 | >62.2 | 6.25 | >42 | 25 | ≤0.39–>62.2 | 6.25–3.12 | >25–>42 | ≤0.39–6.25 | 1.00 | 0.62 | 2.0 | 0.25 |
| Δcna1 mutant | >25 | >62.2 | 6.25 | >42 | 6.25 | ≤0.39–≤0.06 | ≤0.39–1.56 | >25–>42 | ≤0.39–6.25 | 0.008 | 0.25 | 2.0 | 1.00 |
| Δfrr1 mutant | >25 | >62.2 | 6.25 | >42 | 25 | ≤0.39–>62.2 | ≤0.39–3.12 | >25–>42 | ≤0.39–25 | 1.00 | 0.50 | 2.0 | 1.00 |
a
L6, L-685,818; BF, bafilomycin A1; FL, fluconazole; Li, LiCl; MK, MK-0991/caspofungin acetate. For calculation purposes, MICs of >25, >42, >62.2, ≤0.39, and ≤0.06 μg/ml were assumed to be 50, 84, 124.4, 0.19, and 0.03 μg/ml, respectively.