What is the recommended diagnostic work‑up and management for recurrent vaginal candidiasis (≥ three episodes in twelve months)?

Management of Recurrent Vaginal Yeast Infections

For recurrent vulvovaginal candidiasis (≥3 episodes in 12 months), obtain vaginal cultures before starting treatment to identify the Candida species, then initiate a two-phase regimen: induction therapy with fluconazole 150 mg on days 1,4, and 7 (or 7–14 days of topical azole), followed immediately by maintenance fluconazole 150 mg weekly for 6 months. 1

Diagnostic Work-Up

Culture is mandatory before initiating maintenance therapy because 10–20% of recurrent cases are caused by Candida glabrata, which is intrinsically resistant to fluconazole and will waste months of therapy if treated empirically. 1

Essential Diagnostic Steps

• Obtain vaginal culture with species identification and antifungal susceptibility testing in all recurrent/complicated cases and in patients with prior azole exposure. 2

• Collect vaginal secretions spread directly onto a microscopy slide (preferred over swabs for microscopy) to visualize pseudohyphae, though note that C. glabrata forms only yeast cells without filaments. 2

• Use semi-quantitative culture techniques on fungal selective agar to confirm infection versus colonization. 2

• PCR testing provides superior diagnostic performance (sensitivity ≈90% vs. 58% for microscopy; specificity ≈94% vs. 89%) and should be used when available. 1

Critical Diagnostic Pitfall

Never rely on wet-mount microscopy alone—it may be negative even with active infection, and sensitivity is only 57.5%. 1 If microscopy is negative but clinical suspicion remains high, culture is essential. 1

Treatment Algorithm for Candida albicans (Most Common Species)

Phase 1: Induction Therapy

Choose one of the following regimens to achieve mycologic remission:

• Fluconazole 150 mg orally on days 1,4, and 7 (preferred for convenience) 1

OR

• Topical azole applied daily for 7–14 days: 1
  • Clotrimazole 1% cream 5 g intravaginally daily for 7–14 days
  • Miconazole 2% cream 5 g intravaginally daily for 7 days
  • Terconazole 0.4% cream 5 g intravaginally daily for 7 days

Phase 2: Maintenance Therapy

Immediately after induction, begin fluconazole 150 mg orally once weekly for 6 months without interruption. 1, 3 This regimen:

• Controls symptoms in >90% of patients during the 6-month treatment period 1
• Improves quality of life in 96% of women 1
• However, is not curative—30–40% of women experience recurrence after stopping therapy 1

Alternative Maintenance Regimens (When Fluconazole Contraindicated)

• Clotrimazole 500 mg vaginal suppository once weekly 1
• Ketoconazole 100 mg orally daily (requires liver enzyme monitoring; hepatotoxicity risk ≈1/10,000–15,000) 1
• Itraconazole 400 mg orally once monthly 1

Treatment of Non-Albicans Species (C. glabrata)

If culture identifies C. glabrata, do not use fluconazole—it will fail. 1 Instead:

First-Line for C. glabrata

• Boric acid 600 mg intravaginal gelatin capsules daily for 14–21 days (achieves 70% eradication rate) 1

Alternative Options

• Nystatin 100,000-unit suppositories intravaginally daily for 14 days 1
• Compounded topical 17% flucytosine cream ± 3% amphotericin B cream intravaginally nightly for 14 days 1

Special Populations

Pregnancy

Oral fluconazole is contraindicated during pregnancy due to associations with spontaneous abortion and congenital malformations. 1 Use only:

• 7-day course of topical azole therapy (butoconazole, clotrimazole, miconazole, or terconazole) 1

HIV-Positive Women

• Apply the same diagnostic work-up and treatment protocols as for HIV-negative women 1
• Response rates are comparable regardless of HIV status 1

Expected Outcomes & Patient Counseling

Be realistic with patients about recurrence risk:

• During the 6-month maintenance course, >90% achieve symptom control 1
• After completing maintenance therapy, 63% of women continue having infections 1
• A 40–50% recurrence rate should be anticipated after stopping therapy 1

Critical Pitfalls to Avoid

• Never start empiric fluconazole maintenance without confirming species by culture—you may be treating resistant C. glabrata for months with no benefit 1

• Never assume treatment failure means resistance—consider pH effects first: all antifungals have significantly reduced activity at vaginal pH 4 versus pH 7, which explains many "treatment failures" with standard susceptibility testing 1

• Do not treat asymptomatic Candida colonization, which occurs in 10–20% of healthy women and does not require therapy 1

• Do not advise over-the-counter self-treatment unless the woman has a previously documented episode with identical recurrent symptoms; otherwise, appropriate care may be delayed 1

Partner Management

• Routine treatment of male sexual partners is not recommended and does not reduce recurrence rates 1
• Treat partners only if they present with symptomatic balanitis (erythema and pruritus of the glans) using topical antifungal agents 1

Monitoring During Maintenance Therapy

• Schedule regular follow-up visits to assess treatment effectiveness and monitor for adverse effects 1
• Monitor for drug-drug interactions with fluconazole, including calcium-channel antagonists, warfarin, oral hypoglycemics, phenytoin, protease inhibitors, and rifampin 1
• When ketoconazole is used, perform periodic liver enzyme testing 1