Tacrolimus, not triamcinolone acetonide, interacts synergistically with itraconazole, terbinafine, bifonazole, and amorolfine against clinical dermatophyte isolates - 16/10/18

Doi : 10.1016/j.mycmed.2018.09.003

J. Zhang ^a,^{^{1
Jinqing Zhang and Jingwen Tan contributed equally to this study and are joint first authors.}}, J. Tan ^b,^{^{1
Jinqing Zhang and Jingwen Tan contributed equally to this study and are joint first authors.}}, L. Yang ^b,^⁎ , Y. He ^a,^⁎
^a Department of dermatology, Beijing Chao-Yang Hospital, Capital Medical University Beijing, 100020 Beijing, China
^b Department of Medical Mycology, Shanghai Dermatology Hospital, 200443 Shanghai, China

^⁎Corresponding authors.

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Abstract

Objectives

To 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 methods

The interactions between TAC or TRI with antifungal agents were tested according to the microdilution checkerboard technique adapted from the CLSI M38-A2 microdilution method.

Results

TAC 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.