An Update on the Treatment of Vulvovaginal Candidiasis

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As trusted women’s health care providers, Certified Nurse Midwives (CNMs) and Certified Midwives (CMs) provide a range of holistic care to women during pregnancy and the postpartum period; however, many CNM/CMs also provide care to women throughout their lifespan.  Indeed, because of the trust, rapport and relationships that develop during pregnancy and birth, some women choose a midwife as their primary care provider. 

One condition that impacts approximately 75% of women during their lifetime and that CNM/CMs are well versed in diagnosing and treating is Vulvovaginal Candidiasis (VVC).1  Of the 10 million office visits to women’s health care providers for vaginal and vulvar symptoms, VVC infections account for approximately 20-25%. In addition, up to 45% of women will have recurrent VVC, which is defined as >4 infections per year, while 30% will have 6 to20 episodes in their lifetime.3 During pregnancy, approximately 10% of women develop VVC. 

Though 85-95% of cases of VVC are caused by Candida albicans, the remaining 5 to 15% of infections are caused by non-albicans Candida (NAC). As more providers encounter women with resistant or persistent symptoms, the use of cultures and Nucleic Acid Amplification Testing (NAAT) for more accurate diagnosis has revealed many other Candida species that are causative, including C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis.46  Women with recurrent VVC are twice as likely to have a NAC species.7 

Despite the profound impact that both acute and recurrent VVC may have on a woman’s physical and psychological well-being, many clinicians dismiss VVC as “just a yeast infection.” However, VVC may impact several aspects of a woman’s well-being simultaneously, ranging from changes in self-esteem, personal embarrassment, and reduced confidence, to fears of being stigmatized not only by partners, but also by providers. In addition, many women experience an interruption in their sexual function and satisfaction. It’s also important to note that for women with recurrent VVC, there is the added burden of multiple office visits, with a concomitant disruption in their productivity.8-11 

Until recently, there has only been one class of treatment, azoles, available to treat VVC. Though ubiquitous, many clinicians are not aware that azoles are fungistatic and not fungicidal (meaning the agent does not “kill” the offending pathogen). The azole class of medications includes over the counter and prescription vaginal creams comprising butoconazole, clotrimazole, miconazole and terconazole. In addition, a prescription oral preparation, fluconazole, is available and is most frequently prescribed as women and providers prefer an oral treatment.   Unfortunately, fluconazole is not effective in over 30% of women, does not have broad spectrum activity against NAC and there has been increasing antifungal resistance reported over the last 20 years.12 

With recurrent VVC, many women and their providers are frustrated by the lack of efficacy with the current azole treatments and often resort to using boric acid suppositories with varying degrees of success.   

Clinicians have lived with a gap in treatment options for decades. Recently, the FDA approved a new medication to treat VVC, BREXAFEMME® (ibrexafungerp tablets). BREXAFEMME is a fungicidal triterpenoid with a novel mechanism of action that works to break down the fungal cell wall, killing the cell. This is different from azoles, which are fungistatic.  Unlike oral fluconazole, which delivers a vaginal tissue to plasma ratio of 1:1, the concentration of BREXAFEMME in the vaginal tissue is 9 times greater than the levels in the serum, and it also maintains activity in a low pH environment often encountered in the vagina.  

In the two phase 3 clinical trials, a clinical cure was defined as a complete resolution of signs and symptoms at day 10 and complete resolution of symptoms at day 25.  At both time points, there was a statistically significantly greater percentage of women who had a clinical cure on BREXAFEMME than on placebo. BREXAFEMME also demonstrated a sustained efficacy at day 25 with a greater number of women having complete resolution of symptoms.  Women took the 1-day treatment, which consists of 2-150 mg tablets taken twice daily, for a total dosage of 600 mg.. The majority of adverse events included diarrhea, nausea and abdominal pain, however none of the participants dropped out of the trial due to these adverse events. 

As clinicians, we have long recognized the gap in our ability to treat VVC and help our patients return to their lives. We now have a novel 1-day oral treatment that is fungicidal and highly efficacious for our patients with VVC.  

Azie N, et al. Expert Opin Investig Drugs. 2020;29(9):893-900.  2.  Anderson MR. JAMA. 2004;291(11):1368-1379. 3. Johnson et al. J Low Genit Tract Dis. 2010;14(4):287-294.  4. Sobel JD. Lancet. 2007;369(9577):1961-1971. 5. Sobel JD. Am J Obstet Gynecol2016;214(1):15-21. 6. Willems HME, et al. J Fungi (Basel). 2020;6(1):27. doi:10.3390/jof6010027 7Achkar JM, Fries BC. Clin Microbiol Rev. 2010;23(2):253-273  8. Fukazawa EI, et al. Arch Gynecol Obstet. 2019;300(3):647-650.  9. Denning DW, et al. Lancet Infect Dis. 2018;18(11):e339-e347. doi:10.1016/S1473-3099(18)30103-8. 10. Adolfsson A, et al. Adv Sexual Med. 2017;7:1-19. doi:10.4236/asm.2017.71001. 11. Moshfeghy Z, et al. J Turk Ger Gynecol Assoc. 2020;21(2):90-96. 12. Bulik, C.C., Sobel, J.D. and Nailor, M.D. (2011), Susceptibility profile of vaginal isolates of Candida albicans prior to and following fluconazole introduction – impact of two decades. Mycoses, 54: 34-38.