Management of patients with herpes-associated recurrent vulvovaginal candidiasis

Objective. To develop a diagnostic algorithm, a rational method of treatment, and principles of preconception care in women with herpes-associated recurrent vulvovaginal candidiasis (RVVC).Materials and methods. We examined 68 patients with herpes-associated RVVC and 20 gynecologically healthy women.Results. It has been found that in RVVC it is necessary to study vaginal swab culture with the determination of the microorganism and its biofilm-forming ability in combination with viral DNA detection by the polymerase chain reaction (PCR) in vaginal secretion, determination of the IgG titer to the herpes simplex virus (HSV), the avidity index to HSV I and II. In the presence of laboratory-confirmed RVVC and HSV infection, it is necessary to assume the presence of an atypical course of HSV infection followed by complex antiviral and antimycotic therapy.Conclusion. The use of the developed algorithm of diagnostic and treatment interventions as preconception care makes it possible to address symptoms, reduce relapse rates and extend a non-relapse interval, prepare women with the mixed-infection for favorable pregnancy outcomes.

Oteseconazole: an advance in treatment of recurrent vulvovaginal candidiasis

Recurrent vulvovaginal candidiasis (RVVC) has significant disease, financial and quality-of-life burdens, affects women from all strata of society worldwide, and lacks an approved therapeutic solution. Fluconazole emerged in 2004 as an antifungal for RVVC; it provides symptom control and has been accepted worldwide as a first-line treatment. Its limitations include the development of resistance and a high rate of vulvovaginal candidiasis recurrence after therapy cessation. There is now an improved treatment option on the horizon: oteseconazole – a novel, oral, selective fungal cytochrome P450 enzyme 51 inhibitor, designed to avoid off-target toxicities. In clinical studies to date, oteseconazole has demonstrated impressive efficacy, a positive tolerability profile and hope for a superior RVVC treatment option.

107. A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Oteseconazole (VT-1161) Oral Capsules versus Fluconazole and Placebo in the Treatment of Acute Vulvovaginal Candidiasis Episodes in Subjects with Recurrent Vulvovaginal Candidiasis (ultraViolet)

Background Recurrent vulvovaginal candidiasis (RVVC) affects nearly 138 million women globally each year. Currently there are no FDA approved treatments. The study was conducted to evaluate the efficacy of oral oteseconazole (VT-1161) in the prevention of culture-verified acute VVC episodes through Week 50 and compare the efficacy of oteseconazole and fluconazole in treatment of an acute VVC episode in RVVC subjects. Methods 219 subjects with history of RVVC (≥ 3 acute episodes within prior 12 months) were enrolled at 51 US sites. The study consisted of two phases. Induction Phase: Subjects who presented with a vulvovaginal signs and symptoms score of ≥ 3 and positive KOH test identifying Candida were randomized to either: • 600 mg oteseconazole on Day 1, 450 mg oteseconazole on Day 2 and matching placebo capsules; OR • 3 sequential 150 mg doses (every 72 hours) of over-encapsulated fluconazole together with matching placebo capsules Maintenance Phase: 185 subjects with resolved acute VVC infections (clinical signs and symptoms score of < 3) on Day 14 received: • 150 mg oteseconazole or placebo weekly for 11 weeks • then 37-week Follow-up period Results Study achieved primary and secondary efficacy endpoints. Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with ≥ 1 culture-verified acute VVC episode through Week 50 in the intent-to-treat (P < 0.001). The average percentage of subjects with ≥ 1 culture-verified acute VVC episode through Week 50 was lower in the oteseconazole group (5.1%) compared to the fluconazole/placebo group (42.2%). Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at Day 14; 93.2% oteseconazole group, 95.8% fluconazole/placebo group. The percentage of subjects who had ≥ 1 treatment-emergent adverse event (TEAE) was similar; oteseconazole (54%), fluconazole/placebo (64%). Most TEAEs experienced were mild or moderate severity in both groups and no drug-related SAEs or adverse effects on liver function or QT intervals. Conclusion Oteseconazole was shown to be safe and effective in treatment of acute VVC, treatment of RVVC and prevention of recurrence of acute VVC episodes in RVVC subjects. Oteseconazole was non-inferior to fluconazole for treatment of acute VVC in subjects with RVVC. Disclosures Bassem Maximos, MD, Evofem Biosciences (Scientific Research Study Investigator, Speaker's Bureau)Mycovia Pharmaceutical (Scientific Research Study Investigator)Sage Therapeutics (Scientific Research Study Investigator, Speaker's Bureau) Thorsten Degenhardt, Ph.D, Mycovia Pharmaceuticals (Employee, Shareholder) Karen Person, M.S., Mycovia Pharmaceuticals, Inc. (Employee)Mycovia Pharmaceuticals, Inc. (Employee) Mahmoud Ghannoum, PhD, Mycovia Pharmaceuticals (Grant/Research Support, Research Grant or Support) Stephen Brand, Ph.D, Mycovia Pharmaceuticals (Employee)

719. Susceptibility Testing of Oteseconazole (VT-1161) Against Clinical Isolates from Phase 3 Clinical Studies in Subjects with Recurrent Vulvovaginal Candidiasis

Background Oteseconazole (VT-1161) is a novel, investigational oral therapy that is currently under FDA review for the treatment of recurrent vulvovaginal candidiasis (RVVC). Susceptibility testing was performed on all viable clinical isolates collected from three Phase 3 studies to determine the susceptibility of causative pathogens to oteseconazole versus the current treatment standard of care, fluconazole. Methods Vaginal cultures were obtained at screening and at all subsequent study visits throughout the duration of the studies (approx. 48 Weeks) and submitted to a central mycology laboratory for fungal species identification and storage. Susceptibility testing was conducted in accordance with the CLSI Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast M27-Ed4. Results Candida albicans was identified as the primary causative pathogen in 87% of women with RVVC presenting with an acute infection, followed by C. glabrata (8%). Other non-albicans species including; C. parapsilosis, C. tropicalis, C. krusei, C. dubliniensis, C. kefyr and Saccharomyces cerevisiae were responsible for < 1% of infections. A total of 1910 isolates were collected. The MIC range, MIC50 and MIC90 values against all isolates for oteseconazole were ≤ 0.0005 to > 0.25, 0.002 and 0.06 µg/mL, respectively. In comparison, the MIC range, MIC50 and MIC90 values for fluconazole were, ≤ 0.06 to > 32, 0.25 and 8 µg/mL respectively. The MIC range, MIC50 and MIC90 values against all C.glabrata isolates for oteseconazole were 0.002 to > 0.25, 0.03 and 0.125 µg/mL, respectively. In comparison, the MIC range, MIC50 and MIC90 values for fluconazole were, ≤ 0.06 to 32, 2 and 8 µg/mL respectively. Conclusion Oteseconazole demonstrated very low MIC values against most Candida strains, including fluconazole resistant isolates, aligning with clinical study outcomes. Oteseconazole MICs against C. glabrata strains were approximately 6-fold lower than fluconazole. Disclosures Mahmoud Ghannoum, PhD, Mycovia Pharmaceuticals (Grant/Research Support, Research Grant or Support) Thorsten Degenhardt, Ph.D, Mycovia Pharmaceuticals (Employee, Shareholder) Karen Person, M.S., Mycovia Pharmaceuticals, Inc. (Employee)Mycovia Pharmaceuticals, Inc. (Employee) Stephen Brand, Ph.D, Mycovia Pharmaceuticals (Employee)

A Complex Microbial Interplay Underlies Recurrent Vulvovaginal Candidiasis Pathobiology

While extremely prevalent, painful, and difficult to treat, vulvovaginal candidiasis remains largely understudied in the field of women’s health. In a recent issue of mSystems , McKloud et al. (E.

The efficacy of the boric acid-based maintenance therapy in preventing recurrent vulvovaginal candidiasis

Current gold-standard treatment of recurrent vulvovaginal candidiasis (RVVC) is mainly based on maintenance with fluconazole. Moderate to high recurrence rates at long-term use and secondary fluconazole resistance emerge as reasons to seek for new topical maintenance regimens. In this study, it is aimed to assess the efficacy and safety of boric acid-based treatment approach to treat clinical RVVC. In this retrospective study, patients who were diagnosed with RVVC received a treatment package for six months that consist of induction with boric acid vaginal suppositories 600 mg daily for 14 nights followed by maintenance for five nights starting with every fifth day of the menstrual cycles; a vaginal estriol-lactobacilli combination; and several rigorous life-style changes. The success was defined as the absence of symptomatic recurrence during the follow-up. Success rate at the first year was found to be 94.8% in a total of 173 patients. Mild, reversible side effects were observed in five patients (2.9%). Boric acid, along with a vaginal estriol-lactobacilli combination and lifestyle changes can be a safe and effective alternative in lieu of potent systemic antifungal drugs as a first-line treatment for the patients referred with RVVC.