title: In vitro interaction of terbinafine with itraconazole, fluconazole, amphotericin B and 5-flucytosine against Aspergillus spp.
abstract: We investigated the in vitro interaction of terbinafine with itraconazole, fluconazole, amphotericin B and 5-flucytosine, against Aspergillus spp. We tested three isolates of Aspergillus fumigatus (one resistant to itraconazole), and two each of Aspergillus flavus, Aspergillus niger and Aspergillus terreus. We employed a broth microdilution-based method derived from an in vivo validated method capable of detecting itraconazole resistance in A. fumigatus. We studied the effect on the MICs by calculation of the fractional inhibitory concentration (FIC) and fractional fungicidal concentration (FFC) (99.99% kill). Itraconazole and terbinafine were synergic or additive in all strains (FIC = 0.15-1.0). Fluconazole and terbinafine were synergic with A. fumigatus, A. terreus and A. flavus (FIC = 0.3-0.5) and indifferent with A. niger (FIC = 2) isolates. Amphotericin B and terbinafine were mostly indifferent or antagonistic (FIC = 1.0-4.02). Flucytosine and terbinafine were usually indifferent or antagonistic (FIC = 0.63-8.5). FFCs were generally in accord with FICs. The use of terbinafine in combination therapy for Aspergillus infections with azoles seems promising, whereas terbinafine and amphotericin B or flucytosine in combination were less effective.
authors.affiliation: School of Medicine, University of Manchester, Hope Hospital, Salford, Manchester M6 8HD, UK.
authors.forename: J
authors.initials: J
authors.lastname: Mosquera
authors.forename: A
authors.initials: A
authors.lastname: Sharp
authors.forename: C B
authors.initials: CB
authors.lastname: Moore
authors.forename: P A
authors.initials: PA
authors.lastname: Warn
authors.forename: D W
authors.initials: DW
authors.lastname: Denning
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects* / Q000302:isolation & purification; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D015725:Fluconazole / Q000494:pharmacology; D005437:Flucytosine / Q000494:pharmacology; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D009281:Naphthalenes / Q000494:pharmacology; D000077291:Terbinafine
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine; D000077291:Terbinafine