What is the best treatment approach for a patient with persistent vulvovaginal candidiasis, considering potential underlying factors such as diabetes, immunosuppression, or frequent antibiotic use?

Treatment of Persistent Vulvovaginal Candidiasis

For persistent (recurrent) vulvovaginal candidiasis, initiate 10-14 days of induction therapy with either topical or oral azole antifungals, followed by fluconazole 150 mg once weekly for 6 months as maintenance therapy. 1

Initial Diagnostic Confirmation

Before treating persistent disease, confirm the diagnosis and identify the causative species:

• Obtain vaginal cultures to verify Candida infection and identify non-albicans species, particularly C. glabrata, which occurs in 10-20% of recurrent cases and responds poorly to conventional azoles 1
• Verify vaginal pH <4.5 (higher pH suggests bacterial vaginosis or trichomoniasis instead) 2
• Perform wet mount with 10% potassium hydroxide to demonstrate yeast or hyphae 1
• Investigate underlying risk factors: uncontrolled diabetes, immunosuppression, frequent antibiotic use, or hormone replacement therapy 3, 4

Treatment Algorithm for C. albicans Recurrent Disease

Phase 1: Induction Therapy (Achieve Mycologic Remission)

Choose one of the following regimens for 10-14 days:

• Topical azole therapy daily for 7-14 days (clotrimazole, miconazole, terconazole) 1
• Fluconazole 150 mg every 72 hours for 3 doses 1, 2
• Either approach achieves >90% initial response rates 1

Phase 2: Maintenance Therapy (Prevent Recurrence)

After achieving clinical and mycologic remission, initiate suppressive therapy for at least 6 months:

• Fluconazole 150 mg once weekly (most convenient and well-tolerated, controls symptoms in >90% of patients) 1, 5
• Alternative: Clotrimazole 500 mg vaginal suppository once weekly 1
• Alternative: Clotrimazole 200 mg intravaginally twice weekly 1, 6
• Alternative: Ketoconazole 100 mg daily (requires hepatotoxicity monitoring—check liver enzymes, as 1 in 10,000-15,000 develop hepatotoxicity) 1
• Alternative: Itraconazole 400 mg once monthly or 100 mg daily 1

Treatment for Non-Albicans Species (C. glabrata)

When azole therapy fails or C. glabrata is identified:

• First-line: Boric acid 600 mg intravaginally daily for 14 days (preferred alternative per IDSA guidelines) 1, 6
• Second-line: 17% flucytosine cream alone or combined with 3% amphotericin B cream daily for 14 days (must be compounded by pharmacy) 1, 6
• Nystatin intravaginal suppositories 2
• Voriconazole and standard azoles are frequently unsuccessful for C. glabrata 1

Critical Caveats and Common Pitfalls

Expected Recurrence Rates

• After discontinuing maintenance therapy, expect 40-50% recurrence rate 1, 2
• During prophylaxis with placebo, two-thirds of patients develop recurrence within 6 months 7
• Long-term or indefinite maintenance therapy may be warranted for some patients 3

Avoid Misdiagnosis

• Symptoms of VVC (pruritus, irritation, discharge) are nonspecific and can result from various infectious and non-infectious etiologies 1
• Women who self-diagnose may miss other causes or concurrent infections 3
• Unnecessary use of over-the-counter preparations can delay treatment of other conditions and lead to adverse outcomes 1

Special Populations

• Pregnancy: Use only topical azole therapy for 7 days—oral fluconazole is contraindicated due to association with spontaneous abortion 6, 2
• HIV-positive women: Treat identically to HIV-negative women—expect identical response rates 1, 6
• Postmenopausal women: Investigate hormone replacement therapy, diabetes, and immunosuppression as risk factors 4

Partner Management

• Treatment of male sex partners is not routinely recommended but may be considered in women with recurrent infection 1
• Male partners with symptomatic balanitis (erythematous glans with pruritus) benefit from topical antifungal treatment 1

Drug Interactions with Oral Azoles

• Monitor for interactions with astemizole, calcium channel antagonists, cisapride, warfarin, cyclosporine, oral hypoglycemics, phenytoin, protease inhibitors, tacrolimus, terfenadine, theophylline, and rifampin 1

Follow-Up Strategy

• No routine follow-up needed if asymptomatic 1
• Return only if symptoms persist or recur within 2 months 1
• For treatment-resistant cases, obtain repeat cultures to reassess species and consider non-albicans Candida 1
• Monitor compliance with maintenance therapy, as adherence is better with oral regimens than topical preparations 3