Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates

• Main Authors: Laura Bedin Denardi, Débora Alves Nunes Mario, Érico Silva Loreto, Janio Morais Santurio, Sydney Hartz Alves
• Format: Article
• Language: English
• Published: Sociedade Brasileira de Microbiologia 2015-03-01
• Series: Brazilian Journal of Microbiology
• Subjects: Candida glabrata; azole resistance; FK506; combination therapy
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1517-83822015000100125&lng=en&tlng=en

In vitro interaction between tacrolimus (FK506) and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole) against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%), followed by that of the combination with ketoconazole (37%), against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata, a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%), itraconazole (73%), voriconazole (63%) and fluconazole (60%). The synergisms that we observed in vitro, notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.