title: Activities of triazole-echinocandin combinations against Candida species in biofilms and as planktonic cells.
abstract: Biofilm formation complicates the treatment of various infections caused by Candida species. We investigated the effects of simultaneous or sequential combinations of two triazoles, voriconazole (VRC) and posaconazole (PSC), with two echinocandins, anidulafungin (AND) and caspofungin (CAS), against Candida albicans and Candida parapsilosis biofilms in comparison to their planktonic counterparts. Antifungal activity was assessed by the 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide (XTT) metabolic assay. Antifungal-agent interactions were analyzed by the Bliss independence model in the simultaneous-treatment studies and by analysis of variance (ANOVA) in the sequential-treatment studies. Against C. albicans planktonic cells, the simultaneous combination of PSC (32 to 128 mg/liter) and CAS (0.008 to 0.25 mg/liter) was synergistic; the combinations of PSC (128 to 1,024 mg/liter) with AND (0.03 to 0.5 mg/liter) and VRC (32 to 512 mg/liter) with AND (0.008 to 0.03 mg/liter) were antagonistic. Against C. parapsilosis planktonic cells, the interaction between VRC (32 to 1,024 mg/liter) and CAS (1 to 16 mg/liter) was antagonistic. All simultaneous antifungal combinations demonstrated indifferent interactions against biofilms of both Candida species. Damage to biofilms of both species increased (P<0.01) in the presence of subinhibitory concentrations of echinocandins (0.008 to 0.064 mg/liter), followed by the addition of PSC (512 mg/liter for C. albicans and 64 to 512 mg/liter for C. parapsilosis) or VRC (256 to 512 mg/liter for C. albicans and 512 mg/liter for C. parapsilosis). Triazole-echinocandin combinations do not appear to produce antagonistic effects against Candida sp. biofilms, while various significant interactions occur with their planktonic counterparts.
authors.affiliation: 3rd Department of Pediatrics, Aristotle University, Hippokration Hospital, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Chatzimoschou
authors.forename: Aspasia
authors.initials: A
authors.lastname: Katragkou
authors.forename: Maria
authors.initials: M
authors.lastname: Simitsopoulou
authors.forename: Charalampos
authors.initials: C
authors.lastname: Antachopoulos
authors.forename: Elpiniki
authors.initials: E
authors.lastname: Georgiadou
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roilides
mesh_terms: D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002175:Candida / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects; D000077336:Caspofungin; D054714:Echinocandins / Q000494:pharmacology*; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D010933:Plankton / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D011743:Pyrimidines; D014230:Triazoles; C101425:posaconazole; D000077612:Anidulafungin; D000077336:Caspofungin; D065819:Voriconazole