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
Handouts
  • 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.

    Methods: 

    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.

    Results: 

    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).

    Conclusion: 

    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

    Disclosures:

    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.