title: In vitro interactions of anidulafungin with azole antifungals, amphotericin B and 5-fluorocytosine against Candida species.
abstract: Anidulafungin, an echinocandin, is in late stage development for the treatment of fungal infections. We investigated the activity of anidulafungin in combination with other antifungal agents (fluconazole, itraconazole, ketoconazole, amphotericin B and 5-fluorocytosine) against four isolates each of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis, and two isolates of Candida krusei using a macrobroth chequerboard method with interactions evaluated by fractional inhibitory concentration indices (FICIs). Additive activity (FICI > 0.5 to 1) or indifference (FICI > 1 to < 4) was observed in 85 of 90 interactions of anidulafungin with another antifungal agent. Synergy with itraconazole (FICI<or=0.5) was observed for one strain of C. glabrata, and antagonism with ketoconazole (FICI>or=4), a drug rarely used systemically, was noted for four strains of C. tropicalis. The combination of anidulafungin and amphotericin B demonstrated additive activity for each of the 18 isolates of Candida tested. These results suggest additional studies are warranted, for example in animal models, to evaluate further the potential of combination antifungal therapy with anidulafungin for Candida infections.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Man., Canada R3A 1R9. jkarlowsky@hsc.mb.ca
authors.forename: James A
authors.initials: JA
authors.lastname: Karlowsky
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Hoban
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
authors.forename: Beth P
authors.initials: BP
authors.lastname: Goldstein
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage*; D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D002176:Candida albicans / Q000187:drug effects / Q000302:isolation & purification; D041221:Candida glabrata / Q000187:drug effects / Q000302:isolation & purification; D041022:Candida tropicalis / Q000187:drug effects / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D004347:Drug Interactions; D054714:Echinocandins; D005437:Flucytosine / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000008:administration & dosage*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D010456:Peptides, Cyclic; D000666:Amphotericin B; D000077612:Anidulafungin; D005437:Flucytosine