Table 1.

Synergistic in vitro activities of FK506 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 typeMIC (μg/ml) ofa:FIC index
Agent aloneAgents combined
FKBFFLLiMKFK+BFFK+FLFK+LiFK+MKFK+BFFK+FLFK+LiFK+MK
H9912.5>62.26.25>4212.5≤0.39–≤0.06≤0.39–1.5625–>42≤0.39–6.250.0080.252.00.51
Δcna1mutant>25>62.26.25>426.25≤0.39–≤0.06≤0.39–1.5625–>42≤0.39–6.250.0080.251.51.00
Δfrr1mutant>25>62.26.25>4225≤0.39–62.2≤0.39–1.5625–>42≤0.39–251.000.251.51.00
  • a FK, FK506; 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.