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

• Published in: Brazilian journal of microbiology Vol. 46; no. 1; pp. 125 - 129
• Main Authors: Denardi, Laura Bedin, Mario, Débora Alves Nunes, Loreto, Érico Silva, Santurio, Janio Morais, Alves, Sydney Hartz
• Format: Journal Article
• Language: English
• Published: Brazil Springer Nature B.V 01.05.2015; Sociedade Brasileira de Microbiologia
• Subjects: Antifungal Agents - pharmacology; Azoles - pharmacology; Candida glabrata - drug effects; Candida glabrata - isolation & purification; Candidiasis - microbiology; Drug Resistance, Bacterial; Drug Synergism; Drug therapy; Fungi; Humans; Infections; Medical Microbiology; Microbial Sensitivity Tests; MICROBIOLOGY; Studies; Tacrolimus - pharmacology; azole resistance; combination therapy; Candida glabrata; FK506
• ISSN: 1678-4405; 1517-8382; 1678-4405
• DOI: 10.1590/s1517-838246120120442

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.