title: Antifungal activities of tacrolimus in combination with antifungal agents against fluconazole-susceptible and fluconazole-resistant Trichosporon asahii isolates.
abstract: The antifungal activity of tacrolimus in combination with antifungal agents against different fungal species has been previously reported. Here we report the in vitro interactions between tacrolimus and amphotericin B, fluconazole, itraconazole, and caspofungin against 30 clinical isolates of both fluconazole-susceptible and fluconazole-resistant Trichosporon asahii. For these analyses, we used the broth microdilution method based on the M27-A3 technique and checkerboard microdilution method. Tacrolimus showed no activity against T. asahii strains (minimal inhibitory concentrations, MICs>64.0μgmL-1). However, a larger synergistic interaction was observed by the combinations tacrolimus+amphotericin B (96.67%) and tacrolimus+caspofungin (73.33%) against fluconazole-susceptible isolates. Combinations with azole antifungal agents resulted in low rates of synergism for this group (fluconazole+tacrolimus=40% and itraconazole+tacrolimus=10%). Antagonistic interactions were not observed. For the fluconazole-resistant T. asahii group, all tested combinations showed indifferent interactions. The synergism showed against fluconazole-susceptible T. asahii isolates suggests that the potential antifungal activity of tacrolimus deserves in vivo experimental investigation, notably, the combination of tacrolimus with amphotericin B or caspofungin.
authors.affiliation: Universidade Federal de Santa Maria (UFSM), Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Santa Maria, RS, Brazil; Universidade Regional Integrada do Alto Uruguai e das Missões (URI), Santiago, RS, Brazil.
authors.forename: Thaís Felli
authors.initials: TF
authors.lastname: Kubiça
authors.affiliation: Universidade Federal de Santa Maria (UFSM), Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Santa Maria, RS, Brazil.
authors.forename: Laura Bedin
authors.initials: LB
authors.lastname: Denardi
authors.affiliation: Universidade Federal de Santa Maria (UFSM), Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Santa Maria, RS, Brazil.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Azevedo
authors.affiliation: Universidade Federal de Santa Maria (UFSM), Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Santa Maria, RS, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Oliveira
authors.affiliation: Complexo Hospitalar Santa Casa, Porto Alegre, RS, Brazil.
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Severo
authors.affiliation: Universidade Federal de Santa Maria (UFSM), Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Santa Maria, RS, Brazil; Universidade Federal de Santa Maria (UFSM), Departamento de Microbiologia e Parasitologia, Santa Maria, RS, Brazil.
authors.forename: Janio Morais
authors.initials: JM
authors.lastname: Santurio
authors.affiliation: Universidade Federal de Santa Maria (UFSM), Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Santa Maria, RS, Brazil; Universidade Federal de Santa Maria (UFSM), Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Santa Maria, RS, Brazil; Universidade Federal de Santa Maria (UFSM), Departamento de Microbiologia e Parasitologia, Santa Maria, RS, Brazil. Electronic address: sydneyalves.ufsm@gmail.com.
authors.forename: Sydney Hartz
authors.initials: SH
authors.lastname: Alves
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D065095:Calcineurin Inhibitors / Q000494:pharmacology*; D000077336:Caspofungin; D004347:Drug Interactions; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D055666:Lipopeptides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D016559:Tacrolimus / Q000494:pharmacology*; D014250:Trichosporon / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D054714:Echinocandins; D055666:Lipopeptides; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D000077336:Caspofungin; D016559:Tacrolimus
keywords: FK506; Resistance; Susceptibility; Synergism