887. Evaluation of the Broad-Spectrum Antimicrobial Activity of TDT 067 (Terbinafine in Transfersome®) Against Dermatophytes, Yeasts, Filamentous Fungi, and Bacteria
Session: Poster Abstract Session: Antifungal Therapy
Saturday, October 22, 2011
Room: Poster Hall B1
  • TDT 067 IDSA broad spectrum poster 887 for upload.pdf (204.4 kB)
  • Background:

    TDT 067 is a novel carrier-based dosage form of terbinafine in Transfersome® (1.5% spray; developed by Targeted Delivery Technologies Ltd.) in development for onychomycosis. This study compared the antimicrobial activity of TDT 067 and naked terbinafine against dermatophytes, yeasts, filamentous fungi, and bacteria.


    Minimum inhibitory concentrations (MICs) of TDT 067 and naked terbinafine were determined for Trichophyton rubrum (n=5), T. mentagrophytes (n=5), Epidermophyton floccosum (n=5), Candida albicans (n=5), C. parapsilosis (n=6), C. krusei (n=6), C. glabrata (n=6), Cryptococcus neoformans (n=5), Aspergillus fumigatus (n=5), A. flavus (n=5), Rhizopus sp. (n=5), Fusarium solani (n=5), Pseudallescheria boydii (n=6), Nocardia asteroides (n=5), and Actinomadura madurae (n=1) using CLSI standardized methodologies. Minimum fungicidal concentrations (MFCs) were determined by subculturing visually clear wells from the MIC assay for colony count.


    TDT 067 showed potent inhibitory activity and was cidal against dermatophytes (MICs 0.00003−0.015 µg/mL) with MICs lower (mean 8-fold) than terbinafine against all strains. TDT 067 MICs were ≤0.25 µg/mL against C. albicans, C. parapsilosis, and Cr. neoformans, and were lower (mean 3-fold) than terbinafine against all yeast strains, except for C. glabrata for which they were equivalent. In contrast to terbinafine, TDT 067 was cidal against 4/5 Cr. neoformans strains. Results for filamentous fungi were strain specific with TDT 067 MICs lower than terbinafine against 9/10 Aspergillus strains (up to 60-fold lower; MICs 0.002−1 µg/mL), all Rhizopus strains (up to 117-fold lower; MICs 4−8 µg/mL), 1/6 P. boydii strains (30-fold lower; MICs 15−469 µg/mL), and 3/5 Fusarium strains (up to 30-fold lower; MICs 1−234 µg/mL).  TDT 067 MICs were lower than terbinafine against 5/6 strains of bacteria (2−234-fold lower; MICs 4−120 µg/mL).


    The Transfersome® in TDT 067 potentiates the activity of terbinafine. TDT 067 has potent antifungal activity against dermatophyte and non-dermatophyte pathogens of onychomycosis. The antimicrobial activity of TDT 067 extends to other fungi and filamentous bacteria, indicating that TDT 067 may have broader clinical utility.

    Subject Category: M. Mycology including clinical and basic studies of fungal infections

    Mahmoud Ghannoum, PhD1, Nancy Isham, M(ASCP)2, William Henry, PhD3 and Sam Yurdakul, PhD3, (1)Case Western Reserve University/Center For Medical Mycology, Cleveland, OH, (2)Case Western University, Cleveland, OH, (3)Celtic Pharma Development Services Europe Ltd., London, United Kingdom


    M. Ghannoum, Celtic Pharma: Consultant and Speaker's Bureau, Research support
    Merck: Consultant and Speaker's Bureau, Research support
    Pfizer: Consultant and Speaker's Bureau, Research support
    Humco: Consultant, Research support
    NovaBay: Consultant, Research support

    N. Isham, None

    W. Henry, Celtic Pharma Development Services Ltd.: Employee, Salary

    S. Yurdakul, Celtic Pharma Development Services Ltd.: Employee, Salary

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    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.