Clinical Question

Are intravaginal antifungals as safe and effective as oral antifungals for the treatment of uncomplicated vulvovaginal candidiasis?

Evidence-Based Answer

Clinical resolution of symptoms is similar for oral and intravaginal antifungal medications at both short-term (five to 15 days) and long-term (two to 12 weeks) follow-up. (Strength of Recommendation [SOR]: A, based on consistent, good-quality patient-oriented evidence.) However, mycological cure rates (fungal spores cleared from vaginal secretions) are higher in patients treated with oral antifungals at both short-term (number needed to treat [NNT] = 30; 95% CI, 17 to 200) and long-term (NNT = 19; 95% CI, 10 to 91) follow-up.¹ (SOR: C, based on disease-oriented evidence.)

Practice Pointers

Vulvovaginal candidiasis, otherwise known as vaginal thrush, is an infection of the vagina or vulva causing inflammation and discharge as well as irritation and pruritus. In the United States, it is the second most common type of vaginal infection after bacterial infections, and estimates suggest that 75% of women experience at least one episode of vaginal thrush before menopause,² resulting in an estimated 1.4 million annual outpatient visits for vaginal candidiasis in the United States.³ The primary objective of this review is to evaluate whether oral antifungal medications are more effective than intravaginal antifungal medications in the treatment of uncomplicated vulvovaginal candidiasis—defined as occurring in otherwise healthy, nonpregnant women; not associated with severe symptoms; and not recurring more than three times a year.²

This review included 26 randomized controlled trials (5,007 patients) that examined the treatment of vulvovaginal candidiasis with eight antifungals.¹ These trials were conducted within varying demographics in the United States, Europe, Thailand, Iran, Japan, and Nigeria. The eight antifungals studied were oral fluconazole (Diflucan) and itraconazole (Sporanox) and intravaginal butoconazole (Gynazole-1), clotrimazole, econazole (Zolpak), miconazole, sertaconazole (Ertaczo), and terconazole. The effectiveness of oral vs. intravaginal antifungals was evaluated for elimination of symptoms (clinical cure), elimination of yeast remnants found in vaginal secretions (mycological cure), and how often medication adverse effects prevented treatment completion.

Clinical cure rates for patients using short-term courses (five to 15 days) of oral vs. intravaginal antifungals were similar. In 13 clinical trials (1,859 patients), the effectiveness of intravaginal treatment (77% cure rate) was comparable to that of oral treatment (79% cure rate; 95% CI, 75% to 83%). When patients were treated with long-term therapy (defined as two to 12 weeks), clinical cure rates were also similar for patients whether they used intravaginal antifungals (84% cure rate) or oral antifungals (85% cure rate; 95% CI, 80% to 89%) based on the results of nine clinical trials (1,042 patients).

Oral antifungals achieved a higher rate of mycological cure vs. intravaginal antifungals over the short term (NNT = 30; 95% CI, 17 to 200) and the long term (NNT = 19; 95% CI, 10 to 91). The evidence suggests that if the rate of mycological cure at short-term follow-up with intravaginal treatment is 80%, then the cure rate with oral treatment would be 83% (95% CI, 80% to 85%; n = 3,057). For long-term follow-up, if the rate of mycological cure with intravaginal treatment is 66%, then the rate with oral treatment would be 72% (95% CI, 67% to 76%; n = 1,661).

The risk of discontinuing therapy because of adverse effects when using oral or intravaginal antifungals was low. Only three studies described patients discontinuing therapy. Reported adverse effects included headache and gastrointestinal symptoms for oral antifungals and irritation or burning sensation for intravaginal antifungals. Due to the low certainty of evidence, it was unclear whether oral treatments reduced the number of adverse effects compared with intravaginal treatments. The likelihood of adverse effects was the same (12%; 95% CI, 10% to 15%) among patients who used either oral or intravaginal treatment.

Guidelines from the Centers for Disease Control and Prevention suggest either oral or topical treatment for uncomplicated vulvovaginal candidiasis, with longer courses (seven to 14 days) of low-dose topical medication or short courses (one to three days) of higher-dose topical medication considered equivalent to oral therapy with one 150-mg tablet of fluconazole. Follow-up is not typically necessary, nor is treatment of the asymptomatic sex partner.⁴

The practice recommendations in this activity are available at https://www.cochrane.org/CD002845.

Editor’s Note: The NNTs and their corresponding CIs reported in this Cochrane for Clinicians were calculated by the authors based on raw data provided in the original Cochrane review.