title: In vitro activity of the protegrin IB-367 alone and in combination compared with conventional antifungal agents against dermatophytes.
abstract: The occurrence of resistance or side effects in patients receiving antifungal agents leads to failure in the treatment of mycosis. The aim of this experimental study was to investigate the in vitro effects of IB-367 alone and in combination with three standard antifungal drugs, fluconazole (FLU), itraconazole (ITRA) and terbinafine (TERB), against 20 clinical isolates of dermatophytes belonging to three species. Minimum inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), synergy test, time-kill curves, fungal biomass (FB) and hyphal damage using 2,3-bis-(2-methoxy-4-nitro-5-sulfenylamino carbonil)-2H-tetrazolium hydroxide assay (XTT) were performed to study the efficacy of IB-367. In this study, we observed that TERB and ITRA had MICs lower values for all the strains compared to IB-367 and FLU. Synergy was found in 35%, 30% and 25% of IB-367/FLU, IB-367/ITRA and IB-367/TERB interactions respectively. IB-367 exerted a fungicidal activity against Trichophyton mentagrophytes, T. rubrum and Microsporum canis at concentrations starting from 1x MIC. At a concentration of 5x MIC, IB-367 showed the highest rates of hyphae damage for M. canis 53% and T. mentagrophytes 50%; against the same isolates it caused a reduction of 1 log of the total viable count cell hyphae damage. We propose IB-367 as a promising candidate for the future design of antifungal drugs.
authors.affiliation: Department of Dermatology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Oriana
authors.initials: O
authors.lastname: Simonetti
authors.affiliation: Department of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.affiliation: Department of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Arzeni
authors.affiliation: Department of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.affiliation: Department of Dermatology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Conte
authors.affiliation: Department of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Staffolani
authors.affiliation: Department of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Orsetti
authors.affiliation: Department of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Morciano
authors.affiliation: Department of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Castelli
authors.affiliation: Department of Plastic and Reconstructive Surgery, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scalise
authors.affiliation: Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kamysz
authors.affiliation: Department of Dermatology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Offidani
authors.affiliation: Department of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.affiliation: Department of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Barchiesi
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000187:drug effects* / Q000302:isolation & purification; D015169:Colony Count, Microbial; D003881:Dermatomycoses / Q000382:microbiology; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D025301:Hyphae / Q000187:drug effects; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D000077291:Terbinafine
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D009281:Naphthalenes; D017964:Itraconazole; D015725:Fluconazole; D000077291:Terbinafine; C119872:antimicrobial peptide IB-367
keywords: IB‐367; dermatophytes; fluconazole; itraconazole; synergy testing; terbinafine