Efficacy of Topical CD101, a Novel Echinocandin, Against Azole-Resistant Candida albicans in Rat Vulvovaginal Candidiasis

Background:

The efficacy of intravaginally (IVG) administered CD101, a novel, long-acting and highly stable echinocandin formulated as a gel, was compared to miconazole (MCZ) and nystatin (NYS) creams and oral fluconazole (FLU) in an immunosuppressed rat model of vulvovaginal candidiasis (VVC). Gel formulations of CD101 have been shown to be effective against azole-susceptible C. albicans in a similar rat VVC model. Currently marketed echinocandins lack stability to be effectively formulated for topical administration.

Methods:

Estradiol was administered to groups of ovariectomized Wistar rats at 10 mg/kg subcutaneously 3 days before C. albicans (R357) challenge, then maintained with 4 mg/kg weekly injections throughout the study. Animals were immunosuppressed with dexamethasone applied in drinking water (2 mg/L) 3 days before challenge and throughout the study. To establish vaginal infection, anesthetized rats were IVG inoculated with C. albicans (10⁷ CFU) in PBS.  All treatments began 48 hrs after challenge.  CD101 3% gel or 2% MCZ or NYS creams were IVG administered at 0.1 mL/rat once daily for 3 days. Oral FLU 20 mg/kg was administered once daily for 3 days. Rats were sacrificed at days 5 and 12, corresponding to 1 and 8 days after treatment end, followed by vaginal lavage. CFUs were measured in vaginal lavage fluid and tissue.

Results:

A graph of Day 5 and 12 (corresponding to 1 and 8 days after treatment end, respectively) CFUs is shown below. Compared with no treatment control, oral FLU showed minimal (<1 log-fold) reduction in vaginal CFU against the azole-resistant strain of C. albicans.  Topical administration of MCZ cream showed a >2 log-fold reduction in vaginal CFU 1 day after treatment end that rebounded a week later. NYS cream showed >2 log-fold reduction in vaginal CFU 1 day after treatment end that persisted through a week later. CD101 showed the greatest efficacy of the agents tested as vaginal CFUs were below the limit of detection (3.8 log-fold reduction) from 1 day after treatment end and remained >3 log-fold lower for a week after treatment end. Comparable results were also found in vaginal tissue CFUs.

Conclusion:

CD101 was highly effective in eradicating C. albicans when IVG administered as a gel in a rat VVC model with azole-resistant C. albicans.