791. Activity of TOL-463 Against Biofilms Formed by Candida Species in an Ex Vivo Murine Vaginitis Model
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
  • IDWeek 2015 (IDSA Poster 791_C. albicans Explant Study)_FINAL (1).pdf (1.1 MB)
  • Background: TOL-463, a boric acid (BA)-based vaginal anti-infective enhanced with EDTA, is in clinical development for the treatment of lower genital tract infections, with established antibacterial/antifungal activity in planktonic and biofilm assays. Pathogenic biofilms have been implicated as an important virulence attribute of resistance in bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC), resulting in treatment failure and recurrence. Biofilms have been identified on vaginal biopsy in women with genital infections and shown to readily form on vaginal mucosa in vivo and ex vivo in mouse models. The objective of this study was to further characterize the antifungal activity of TOL‑463 against Candida species employing the same ex vivo murine model, which has proven to reflect a robust C. albicans biofilm.  

    Methods: Explant vaginal tissue from estrogenized mice were pre-treated with penicillin-streptomycin and inoculated with 2.5x10C. albicans or C. glabrata clinical or ATCC isolates and incubated for 24 hours at 37°C to allow for biofilm formation. Thereafter, tissues were treated every 24 hours with vehicle (sterile water), BA 50 mg/mL, or TOL-463 test solutions for up to 3 doses. Fungal burden was assessed by enumeration of CFUs per 500µL of homogenized tissue at 24, 48 and 72 hours after the conclusion of each dose regimen.

    Results: TOL-463 was associated with significant reductions in C. albicans and C. glabrata CFUs within 24 hours of the first dose (P < 0.0001). By 72 hours following the third dose, >4 log reductions in CFUs were achieved. Greater inhibition of Candida sp. was demonstrated for TOL-463 compared with BA only by the second dose and the difference was sustained through the final test interval (P < 0.0001).

    Conclusion: TOL-463 was highly effective at inhibiting C. albicans and C. glabrata fungal burden/biofilm formation on vaginal mucosa ex vivo that was superior to BA. These findings are consistent with published data for TOL-463 showing the same advantage, with robust destruction of biofilms formed by C. albicans and G. vaginalis in CDC biofilm reactors. An ex vivo study of TOL-463 against G. vaginalis, a key BV pathogen, is ongoing. TOL-463 holds promise as a non-azole vaginal anti-infective with novel antibiofilm properties.

    Paul Fidel Jr., Ph.D., Oral and Craniofacial Biology, LSU Health Sciences Center School of Dentistry, New Orleans, LA and Elizabeth Lilly, MS, LSU Health Sciences Center School of Dentisry, New Orleans, LA


    P. Fidel Jr., Toltec Pharmaceuticals, LLC: Consultant , Consulting fee

    E. Lilly, None

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