Calcineurin inhibitor FK506 exhibits synergistic antifungal activity with caspofungin against echinocandin resistant strains.

#Strains were grown overnight with shaking at 30°C and washed twice in dH2O. The OD600 was taken of the cultures with a spectrophotometer and diluted to 0.01 OD600/ml in RPMI-1640 medium [Sigma R1383 (8.4g) and MOPS (34.5g) in 1L dH2O buffered to pH7 with NaOH]. Minimum inhibitory concentrations (MIC) of each drug alone and fractional inhibitory concentrations of the drugs in combination were determined using the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) protocol M27-A3. Final concentrations of caspofungin (CAS) ranged from 16 to 0.0312 µg/ml. FK506 concentrations ranged from 4.0 to 0.063 µg/ml.
&FIC index = (MICcombined drug 1/MIC alone drug 1) + (MICcombined drug 2/MICalone drug 2) FIC ≤0.5 (synergy), >0.5 but <1.0 (additive), >1.0 but ≤2.0 (no interaction), >2.0 (antagonism).
*C. lusitaniae clinical echinocandin resistant isolates with the Ser645Phe mutation in the Fks1 protein.