890. Evaluation of the Antifungal Activity of TDT 067 (Terbinafine in Transfersome®) in Combination with Antifungals Used in the Treatment of Systemic Fungal Infections
Session: Poster Abstract Session: Antifungal Therapy
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • TDT 067 IDSA combination study poster 890 for upload.pdf (219.4 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. The effect of combining TDT 067 with caspofungin (CAS) and voriconazole (VOR), used in the treatment of systemic mycoses, was evaluated against relevant fungal species.

    Methods: 

    TDT 067 was tested in combination with CAS against 5 strains each of Candida albicans, C. glabrata, C. krusei, and C. parapsilosis,  and with VOR against 5 strains each of Aspergillus fumigatus, A. flavus, Fusarium solani, and Rhizopus spp. Combination minimum inhibitory concentration (MIC) testing was performed by a checkerboard microdilution assay with 2 antifungal agents combined in varying concentrations to determine whether they had synergistic, indifferent, or antagonistic interactions on the respective MICs. Visually clear wells from the assay were subcultured for colony forming unit (CFU) counts to determine cidality.

    Results: 

    TDT 067 combined with CAS demonstrated synergy against 2 strains of C. albicans (MICs of TDT 067 and CAS up to 16-fold and 62-fold lower, respectively, in combination), and resulted in ≥99.9% reduction in CFUs against all C. krusei and C. glabrata strains tested and 1 C. albicans strain. TDT 067 and VOR in combination demonstrated synergistic interaction against 6/20 strains of the filamentous fungi tested, including 3 A. fumigatus strains (MICs of TDT 067 and VOR up to 4-fold and 16-fold lower, respectively, in combination), 2 Rhizopus strains (MICs of TDT 067 and VOR up to 16-fold and 128-fold lower, respectively, in combination), and 1 A. flavus strain (MICs of TDT 067 and VOR 4-fold lower in combination). The addition of TDT 067 to VOR resulted in ≥99.9% reduction in CFUs against all the Aspergillus strains tested.

    Conclusion: 

    TDT 067 showed synergistic interactions in combination with CAS and VOR, with the greatest effect shown by the combination of TDT 067 and VOR against Aspergillus strains, resulting in fungicidal activity. Importantly, there was no antagonism with the combination of TDT 067 with either antifungal against any of the strains tested. TDT 067 may have clinical utility in combination with antifungals used for treatment of invasive fungal infections.


    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.