Recurrent vulvovaginal candidiasis

Clinical question

What is the most effective management for women with recurrent vulvovaginal candidiasis (≥ 4 episodes within 1 year)?

Bottom line

Prophylaxis with 6 months of azole therapy will reduce relapse to 9% to 19% of women compared with 50% to 64% with placebo (1 fewer woman would relapse for every 2 to 4 treated). However, efficacy declines after therapy cessation and clinical cure remains elusive. Limited evidence suggests women might prefer episodic over maintenance therapy.

Evidence

Two double-blind RCTs of 373¹ and 64 women² with symptoms and culture-confirmed recurrent vulvovaginitis compared 150 mg of oral fluconazole weekly for 6 months (after an initial 150 mg of oral fluconazole every 72 hours for 3 days) with placebo:

• There was a statistically significant difference in clinical relapse rate:

  • -After 6 months’ treatment,^1,2 9% to 19% relapsed versus 50% to 64% (number needed to treat [NNT] = 2 to 4).

• At the 12-month follow-up,¹ 57% had relapsed versus 78% (NNT = 5). There was no significant difference in relapse in the smaller study,² and no increase in resistance in either study.^1,2

• There was 1 case of “mild” elevation of liver enzymes that did not require treatment discontinuation.¹

• Analysis only included those compliant with treatment.¹

  Two RCTs examined 400 mg of oral itraconazole monthly (N = 114)³ and a monthly 500-mg clotrimazole vaginal suppository (N = 62)⁴ versus placebo for 6 months.

• Statistically significant difference in clinical relapse rate: 30% to 36% versus 64% to 79%, NNT = 3 to 4.

• No longer significant at the 12-month follow-up.^3,4

One observational study of 136 women individualized decreasing doses (200 mg of fluconazole 3 times a week, weekly for 2 months, biweekly for 4 months, then monthly for 6 months) based on clinical symptoms⁵:

• There was a 30% clinical relapse rate during 12 months of treatment and a 45% rate at the 18-month follow-up.

Context

• Studies of alternative therapies, such as probiotics or homeopathy, are of poor quality and have mixed results.⁶

• Limited evidence suggests no significant difference among azoles in acute or recurrent Candida albicans vulvovaginitis.⁷

• Candida albicans causes 90% of vulvovaginal candidiasis, followed by Candida glabrata, which is azole resistant.⁸

• A small trial (54 women) showed that treating male sexual partners with antifungals does not reduce relapse.⁹

• A randomized crossover trial of 23 women reported 74% versus 14% prefer to treat each episode empirically versus maintenance therapy.¹⁰

Implementation

Only about one-third of women correctly self-diagnose vulvovaginal candidiasis.¹¹ Yeast culture might be considered if the patient has recurrent infection, has treatment failure, or is immunocompromised. Small studies comparing boric acid (600 mg intravaginally daily for 7 to 14 days) with intravaginal nystatin or oral fluconazole suggest it has limited efficacy, particularly against C glabrata.¹² Boric acid requires pharmacy compounding and might cause vulvovaginal irritation. There are no RCTs examining boric acid as prophylaxis.