What treatment options are available for a patient with monilial (candidal) vaginitis who is resistant to Diflucan (fluconazole) treatment?

Treatment of Fluconazole-Resistant Vulvovaginal Candidiasis

For fluconazole-resistant vulvovaginal candidiasis, switch to intravaginal boric acid 600 mg daily for 14 days as first-line therapy, or alternatively use topical nystatin or extended-course topical azole therapy for 7-14 days. 1

Confirming True Resistance

Before changing therapy, verify the diagnosis and resistance pattern:

• Obtain vaginal cultures to identify the specific Candida species, as non-albicans species (particularly C. glabrata) are inherently less susceptible to fluconazole 1
• Confirm normal vaginal pH (≤4.5) and visualize yeast or pseudohyphae on wet mount with 10% KOH to exclude alternative diagnoses 2, 1
• Consider that treatment failure may represent reinfection, non-compliance, or misdiagnosis rather than true resistance 3

Primary Treatment Options for Resistant Cases

Boric Acid (Preferred for Non-Albicans Species)

Boric acid 600 mg in gelatin capsules intravaginally once daily for 14 days is the recommended first-line treatment for fluconazole-resistant vulvovaginal candidiasis, particularly for C. glabrata infections. 1

• Achieves mycologic cure rates of 64-100% in fluconazole-resistant cases 4, 5
• Particularly effective for C. glabrata, with cure rates of 64.3% compared to only 12.5% with fluconazole 5
• Common adverse effects include vaginal burning sensation (<10% of cases), watery discharge during treatment, and mild vaginal erythema 4

Topical Nystatin (Alternative Option)

• Nystatin vaginal suppositories (100,000 units) intravaginally daily for 14 days can be used for fluconazole-resistant cases 1
• Demonstrated 80.7% mycologic cure rates in recurrent cases, including those caused by fluconazole-resistant Candida 5
• Successfully treated 5 of 9 patients with fluconazole-resistant Candida in maintenance therapy 5

Extended Topical Azole Therapy

For cases where boric acid is unavailable or not tolerated:

• Clotrimazole 1% cream 5g intravaginally daily for 7-14 days 1, 6
• Miconazole 2% cream 5g intravaginally daily for 7 days 1
• Terconazole 0.4% cream 5g intravaginally daily for 7 days 1

Note that topical azoles may have limited efficacy against truly fluconazole-resistant strains, as cross-resistance can occur. 1

Alternative Oral Azole Options

Itraconazole Solution

• Itraconazole oral solution 200 mg once daily for up to 28 days can be considered for fluconazole-refractory disease 2
• However, itraconazole has variable absorption and inferior pharmacokinetics compared to fluconazole 1
• The FDA label notes that itraconazole oral solution achieved approximately 55% complete resolution in patients clinically unresponsive to fluconazole 7

Posaconazole

• Posaconazole suspension 400 mg twice daily for 3 days, then 400 mg daily for up to 28 days is recommended for fluconazole-refractory disease 2

Voriconazole

• Voriconazole 200 mg orally twice daily is an alternative for refractory cases 2

Severe or Refractory Cases Requiring Parenteral Therapy

For severe cases unresponsive to topical and oral options:

• Intravenous echinocandin: caspofungin 70 mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading dose then 100 mg daily 2
• Intravenous amphotericin B deoxycholate 0.3 mg/kg daily 2

These parenteral options should be reserved for truly refractory cases or severely immunocompromised patients, as they represent significant escalation of therapy. 2

Management of Recurrent Fluconazole-Resistant Disease

If resistance develops in the context of recurrent vulvovaginal candidiasis (≥4 episodes per year):

• Use a two-phase approach: induction therapy with boric acid 600 mg daily for 14 days, followed by maintenance suppression with boric acid 600 mg twice weekly for 6 months. 1, 4
• Alternatively, nystatin suppositories can be used for 14 days each month as maintenance therapy 5
• Investigate and correct predisposing factors including immunosuppression, uncontrolled diabetes, antibiotic use, and hormonal factors 1

Critical Pitfalls to Avoid

• Do not continue fluconazole at higher doses or longer durations if true resistance is documented, as this promotes further resistance development 1
• Oil-based topical preparations (creams and suppositories) weaken latex condoms and diaphragms; counsel patients accordingly 6
• Avoid oral fluconazole entirely in pregnant women; use only 7-day topical azole therapy 1, 6
• Do not treat sexual partners unless they have symptomatic balanitis, as vulvovaginal candidiasis is not sexually transmitted 6
• Self-diagnosis is unreliable; always obtain microscopic confirmation before treating presumed recurrent infections 1