Managing Recurrent Vulvovaginal Candidiasis

Case History

A 32-year-old woman presents to her gynecologist with a history of recurrent vulvovaginitis characterized by intense itching, burning sensation, and a thick, cottage cheese-like discharge for 1 year. She reports that she has previously tried multiple courses of oral over-the-counter topical medications, intravaginal boric acid suppositories as well as oral fluconazole including an extended-duration course, but her symptoms persist despite treatment. Vaginal swab fungal culture is now growing Nakaseomyces (formerly Candida) glabrata with resistance to fluconazole. What would be the next best option for treatment?

Managing Vulvovaginal Candidiasis

Vulvovaginal candidiasis (VVC) is a commonly encountered condition and 14%–28% of females experience recurrent VVC, which is defined as more than four episodes in 12 months. ¹

Infectious Diseases Society of America guidelines suggest topical antifungals or a single dose of fluconazole for treatment of uncomplicated VVC and fluconazole 150 mg every 72 hours for two to three doses for severe acute VVC. For VVC caused by N. glabrata which is unresponsive to oral azoles, therapeutic options include topical intravaginal boric acid 600 mg in a gelatin capsule for 14 days, nystatin intravaginal suppositories (100 000 U daily) and topical 17% flucytosine cream alone or in combination with 3% AmB cream administered daily. For recurrent VVC, a 10–14-day course of induction therapy with a topical agent or oral fluconazole, followed by fluconazole 150 mg weekly for 6 months, is recommended. ² Ibrexafungerp (Brexafemme), developed by Scynexis Inc., is an antifungal medication that has shown promising results in the treatment of VVC secondary to drug-resistant Candida species. It was initially approved on June 1, 2021, by the U.S. Food and Drug Administration for the treatment of acute VVC and later approved for prevention of recurrent VVC. ³

Unlike azole antifungals which primarily target the ergosterol synthesis pathway, ibrexafungerp offers a distinct mechanism of action making it an attractive option for treating infections caused by drug-resistant Candida strains. The drug is a triterpenoid antifungal which inhibits the β-1,3-D glucan synthase, a critical component of the fungal cell wall, leading to cell wall instability and ultimately, fungal cell death.

VANISH 303, a phase 3 trial consisting of 376 participants comparing ibrexafungerp with placebo in patients with recurrent VVC demonstrated patients on ibrexafungerp had significantly higher rates of clinical cure (50.5% vs. 28.6%; p = 0.001), mycological eradication (49.5% vs. 19.4%; p < 0.001), and overall success (36.0% vs. 12.6%; p < 0.001) compared with placebo. The medication was well tolerated, and mild adverse events included gastrointestinal symptoms. ⁴

The CANDLE study (phase 3 trial) evaluated the safety and efficacy of monthly ibrexafungerp dosing to reduce the recurrence of yeast infection. Oral Fluconazole 150 mg every 72 hours for three doses followed by Oral Ibrexafungerp 300 mg BID (1 day) every 4 weeks for a total of six dosing days was used in this trial, and demonstrated that 65.4% of patients receiving ibrexafungerp had no VVC recurrences, whether culture-proven, presumed, or suspected, through study week 24. Comparatively, 53.1% of placebo recipients had no recurrences. ⁵

The recommended dosage of ibrexafungerp for VVC is two 150 mg tablets administered ∼12 hours apart for 1 day, with a total dosage of four 150 mg tablets. To reduce the recurrence of VVC, adult and postmenarchal women should continue with this dosing regimen once a month for 6 months. Ibrexafungerp may be taken with or without food.

Treatment Options for VCC

For recurrent VVC, two doses are administered ∼12 hours apart, every month for 6 months. ⁶ It is considerably more expensive than fluconazole, with the cost of a two dose regimen of around $520.

No serious adverse effects have been reported in phase 3 clinical trials. The most common adverse events reported in ibrexafungerp clinical trials for VVC were diarrhea, nausea, abdominal pain, dizziness, and vomiting. During the ibrexafungerp trials for recurrent VVC, the most common side effects were headache, abdominal pain, diarrhea, nausea, urinary tract infection, and fatigue. The safety of the drug is not evaluated in premenarchal patients. It carries a boxed warning for the risk of embryo-fetal toxicity. The medication is contraindicated in pregnant patients based on animal studies. Contraception should be used during treatment followed by 4 days after the last dose. ⁷

Answer: E

As the patient has already tried extended treatment course of fluconazole, vaginal creams, and the current isolate is not susceptible to fluconazole, option A and D, are not the correct choices. Echinocandins have not been well studied or approved for VVC; therefore, option B is not the correct choice. Option C is not correct as Metronidazole has no role in VVC.