370. Efficacy of cochleated amphotericin B (C-AMB) in mouse models of oropharyngeal and vulvovaginal candidiasis
Session: Poster Abstract Session: Fungal Disease: Management and Outcomes
Thursday, October 4, 2018
Room: S Poster Hall
Posters
  • 2018_IDWeek_Poster_CAMB.pdf (1.8 MB)
  • Background: Candida albicans causes debilitating mucosal infections in patients with inherited susceptibility to chronic mucocutaneous candidiasis (CMC) such as oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC), which often require long-term azole-based treatment. Due to the high incidence of azole resistance in these patients, alternative treatment options are desirable. Acquired resistance against amphotericin B (AMB) has not been documented but parenteral administration of AMB is associated with nephrotoxicity and infusion reactions. Cochleated AMB (C-AMB) is a new formulation of AMB designed for oral administration and thus an attractive treatment option for OPC and VVC. The purpose of our study was to assess the efficacy of C-AMB in mouse models OPC and VVC.

    Methods: IL-17 signaling deficient mice (Act1-/-) were infected with a clinical isolate of C. albicans in models of OPC and VVC. From day 1 post-infection (pi) through day 4 pi, mice were treated once daily via oral gavage with C-AMB or placebo or intraperitoneal AMB-deoxycholate (AMB-d). At day 5 pi, the mice were euthanized and tongue tissue (OPC) or vaginal fluid and vaginal tissue (VVC) were harvested to quantify fungal burden.

    Results: During OPC, mice treated with C-AMB (25 or 83.5 mg/kg/day) displayed significantly reduced tongue fungal burden compared to placebo-treated mice and comparable to that observed in mice treated with intraperitoneal AMB-d (25 mg/kg/day). During VVC, mice treated with C-AMB exhibited significantly decreased fungal burden in vaginal tissue, but not vaginal fluid, relative to placebo-treated mice.

    Conclusion: Oral administration of C-AMB in IL-17-signaling deficient mice results in a reduction in tongue and vaginal tissue fungal burden during mucosal C. albicans infections. Ongoing studies are aimed at characterizing the distribution of C-AMB in mouse mucosal tissues and examining C-AMB efficacy relative to fluconazole.

    Jigar V. Desai, PhD1, Ruying Lu, BS2, Alexandra F. Freeman, MD3, Edmund Tramont, MD, FIDSA3, Jerry Jabbour, PhD4, Raphael J. Mannino, PhD2 and Michail S. Lionakis, MD, ScD5, (1)Fungal Pathogenesis Section, Laboratory of Clinical Immunology & Microbiology, NIAID, NIH, Bethesda, MD, (2)Matinas BioPharma, Inc., Bedminster, NJ, (3)National Institute of Allergy and Infectious Diseases, Bethesda, MD, (4)Matinas BioPharma Inc, Bedminster Township, NJ, (5)Laboratory of Clinical Immunology & Microbiology, NIAID/NIH, Bethesda, MD

    Disclosures:

    J. V. Desai, None

    R. Lu, Matinas BioPharma Inc: Employee , Salary .

    A. F. Freeman, Matinas BioPharma Inc: Research Support , Research support .

    E. Tramont, None

    J. Jabbour, Matinas BioPharma Inc: Employee , Salary .

    R. J. Mannino, Matinas BioPharma Inc: Employee , Salary .

    M. S. Lionakis, Matinas BioPharma Inc: Research support , Research support .

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.