Objectives
The efficacy of intravaginally (IVG) administered CD101, a novel, long-acting and highly stable echinocandin formulated as a gel, was compared to marketed miconazole (MCZ) and nystatin (NYS) creams and oral fluconazole (FLU) in an immunosuppressed rat model of vulvovaginal candidiasis (VVC). Gel formulations of CD101 have previously been shown to be effective against azole-susceptible C. albicans in a similar rat VVC model. Currently marketed echinocandins lack chemical stability to be effectively formulated for topical administration.
Methods
Groups of oophorohysterectomized female Wistar rats were used. Estradiol was administered 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 (10 7 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 was also administered at 20 mg/kg once daily for 3 days. Rats were sacrificed at 2 different time points after treatment end (days 5 and 12 corresponding to 1 and 8 days after treatment end) followed by vaginal lavage. C. albicans counts were measured in lavage fluid and in excised vaginal tissue.
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