What is the treatment for recurrent vulvovaginal candidiasis (yeast infections)?

Treatment of Recurrent Vulvovaginal Candidiasis

For recurrent vulvovaginal candidiasis (≥3 episodes per year), treat with 10-14 days of induction therapy using either a topical azole or oral fluconazole, followed by maintenance therapy with fluconazole 150 mg orally once weekly for 6 months. 1

Definition and Diagnosis

• Recurrent VVC (RVVC) is defined as three or more symptomatic episodes within 12 months 1
• Confirm diagnosis with wet mount preparation using 10% potassium hydroxide to visualize yeast or hyphae, and verify normal vaginal pH (≤4.5) before initiating treatment 1, 2
• Obtain vaginal cultures for Candida species identification if wet mount is negative, as this guides therapy selection 1
• Most RVVC cases (>90%) are caused by azole-susceptible Candida albicans 1

Two-Phase Treatment Protocol

Phase 1: Induction Therapy (10-14 days)

Choose one of the following regimens:

• Oral fluconazole 150 mg every 72 hours for 3 doses (days 1,4, and 7) 1
• Topical azole therapy for 10-14 days: clotrimazole 1% cream 5g intravaginally daily, miconazole 2% cream 5g intravaginally daily, or terconazole 0.4% cream 5g intravaginally daily 1, 2

Phase 2: Maintenance Therapy (6 months)

• Fluconazole 150 mg orally once weekly for 6 months is the most convenient and well-tolerated regimen, achieving symptom control in >90% of patients 1
• This maintenance regimen improves quality of life in 96% of women 1
• Alternative maintenance options if fluconazole is not feasible: topical clotrimazole 200 mg twice weekly or clotrimazole 500 mg vaginal suppository once weekly 1

Expected Outcomes and Recurrence Rates

• With weekly fluconazole maintenance, 90.8% of women remain disease-free at 6 months, 73.2% at 9 months, and 42.9% at 12 months 3
• The median time to clinical recurrence with fluconazole maintenance is 10.2 months versus 4.0 months with placebo 3
• After cessation of 6-month maintenance therapy, expect a 40-50% recurrence rate 1
• More than 63% of women who complete maintenance therapy continue to have ongoing infections, indicating that long-term cure remains difficult to achieve 1, 3

Critical Management Considerations

Address Contributing Factors

• Control diabetes and hyperglycemia, as uncontrolled blood sugar promotes candidal growth 1, 2
• Investigate immunosuppression status, particularly HIV infection, in patients with RVVC 2
• Evaluate for other predisposing factors before initiating maintenance therapy 1

Drug Resistance and Non-Albicans Species

• All antifungal medications have higher minimum inhibitory concentrations (MICs) at vaginal pH 4 compared to laboratory pH 7, which may contribute to treatment failure 1
• C. glabrata shows particularly reduced susceptibility at low pH, with terconazole MIC being >388-fold higher at pH 4 than pH 7 1
• For azole-refractory C. glabrata VVC, use boric acid 600 mg in gelatin capsule intravaginally daily for 14 days 1, 2
• Alternative for C. glabrata: topical 17% flucytosine cream alone or combined with 3% amphotericin B cream daily for 14 days (must be compounded by pharmacy) 1
• Azole-resistant C. albicans infections are extremely rare but have been documented after prolonged azole exposure 1

Common Pitfalls to Avoid

• Do not rely on self-diagnosis: less than half of patients treated for VVC have objectively confirmed disease 1
• Do not treat asymptomatic colonization: 10-20% of women normally harbor Candida species without infection 2
• Do not use alternative treatments (honey-based ointments, essential oils, ginger-clotrimazole combinations): these are equal or inferior to FDA-approved medications and lack regulation 1
• Do not discontinue maintenance therapy prematurely: completing the full 6-month course is essential for optimal outcomes 1

Special Population Considerations

Pregnancy

• Avoid oral fluconazole in pregnancy due to association with spontaneous abortion and congenital malformations 1, 2
• Use only topical azole therapy for 7 days in pregnant women 1, 2

HIV-Positive Patients

• Treatment regimens should be identical to HIV-negative women, with equivalent response rates expected 1, 2

When to Reevaluate

• Verify clinical and mycological remission 1 month after completing induction therapy before initiating maintenance 2
• If symptoms persist after 7-14 days of appropriate therapy, reconsider the diagnosis or obtain fungal culture for species identification and susceptibility testing 1, 4
• Reevaluate if symptoms recur within 2 months of treatment completion 2

Emerging Therapies

• Oteseconazole (VT-1161), a novel oral antifungal with long plasma half-life, showed remarkably lower recurrence rates (4% vs 52% placebo) at 48 weeks in clinical trials 1
• A vaccine targeting Candida albicans hyphal virulence factor has shown safety and efficacy in reducing symptomatic VVC frequency for up to 12 months, but only in women under 40 years of age 1