Tacrolimus, not triamcinolone acetonide, interacts synergistically with itraconazole, terbinafine, bifonazole, and amorolfine against clinical dermatophyte isolates

Abstract

ObjectivesTo compare the in vitro interactions between tacrolimus (TAC)/triamcinolone acetonide (TRI) with itraconazole (ITC), terbinafine (TRB), bifonazole (BIZ), and amorolfine (AMF) in 28 clinical dermatophyte isolates, including 13 Trichophyton rubrum, 6 Trichophyton mentagrophytes, 5 Microsporum canis, and 4 Epidermophyton floccosum strains. Materials and methodsThe interactions between TAC or TRI with antifungal agents were tested according to the microdilution checkerboard technique adapted from the CLSI M38-A2 microdilution method. ResultsTAC and TRI did not exhibit significant antifungal activity against the tested strains at the highest concentration (MICs>8μg/mL). However, a strong synergistic interaction was observed for combinations of TAC with ITC (53%), TRB (53%), or BIZ (63%) against Trichophyton strains. Comparatively, TRI/ITC (11%) and TRI/BIZ (16%) combinations showed weaker synergistic activity against the same Trichophyton strains. TAC also showed synergistic interaction with ITC against 20% M. canis strains, with TRB against 60% M. canis strains, and with BIZ against 25% E. floccosum strains. No synergism was observed when M. canis and E. floccosum strains were exposed to TRI in combination with these drugs. Antagonism was not observed for any combinations. ConclusionsCompared with TRI, TAC showed better synergy when combined with antifungal agents, especially topical TRB and BIZ, against dermatophyte isolates.