What is the best treatment approach for a patient with recurring Candida glabrata infection?

Treatment of Recurring Candida glabrata

For recurring Candida glabrata vulvovaginal infections unresponsive to oral azoles, use topical intravaginal boric acid 600 mg daily for 14 days as first-line therapy, followed by long-term suppressive maintenance if needed. 1, 2

Initial Treatment Approach for Acute Episodes

First-Line Therapy

• Topical intravaginal boric acid in gelatin capsules, 600 mg daily for 14 days is the preferred treatment for C. glabrata vulvovaginitis that fails oral azole therapy 1, 2
• This recommendation carries strong evidence despite being based on low-quality studies, reflecting the clinical reality that C. glabrata is intrinsically resistant to fluconazole and other azoles 1, 2, 3

Second-Line Alternatives

• Nystatin intravaginal suppositories, 100,000 units daily for 14 days if boric acid is unavailable or not tolerated 1, 2
• Topical 17% flucytosine cream alone or combined with 3% amphotericin B cream daily for 14 days as a third option 1, 2

Critical Diagnostic Step Before Treatment

• Obtain vaginal cultures to confirm C. glabrata as the causative organism rather than assuming treatment failure is due to this species 1, 2
• Verify the diagnosis with wet-mount preparation (10% KOH) and check vaginal pH (should be 4.0-4.5) 1, 2
• C. glabrata does not form pseudohyphae or hyphae, making microscopic identification challenging 1, 3

Long-Term Suppressive Maintenance Therapy

Maintenance Regimen for Recurrent Infections

Once acute infection is controlled with one of the above regimens:

• Begin with 10-14 days of induction therapy using either topical agents or oral fluconazole (though fluconazole is often ineffective for C. glabrata specifically) 1
• Follow with fluconazole 150 mg weekly for 6 months as maintenance therapy 1
  • This regimen achieves symptom control in >90% of patients with recurrent vulvovaginal candidiasis 1
  • However, note that fluconazole maintenance may be less effective for C. glabrata due to intrinsic azole resistance 1, 2, 3

Alternative Maintenance Options

• Clotrimazole 500 mg vaginal suppository once weekly 1
• Clotrimazole cream 200 mg twice weekly 1
• Consider these topical alternatives specifically for C. glabrata given its reduced azole susceptibility 1, 2

Special Considerations for C. glabrata

Why C. glabrata is Problematic

• C. glabrata has intrinsic reduced susceptibility to all azole antifungals, including fluconazole and voriconazole 1, 2, 4, 3
• This species accounts for 10-20% of recurrent vulvovaginal candidiasis cases 1
• The organism is a haploid yeast that grows as a facultative anaerobe without forming true hyphae 3

Common Pitfalls to Avoid

• Do not use fluconazole as first-line therapy for confirmed C. glabrata infections - it is frequently ineffective 1, 2, 3
• Distinguish between colonization and true infection - the presence of C. glabrata may represent colonization in patients with other underlying conditions 1, 5
• Compounded medications required - boric acid capsules and flucytosine cream must be specially prepared by a compounding pharmacy 1, 2
• Expect high recurrence rates - after stopping maintenance therapy, 40-50% of patients will experience recurrence 1, 2

For Invasive/Systemic C. glabrata Infections

If the recurring infection is systemic rather than localized vulvovaginal disease:

• Echinocandins (caspofungin, micafungin, or anidulafungin) are the preferred agents for invasive C. glabrata disease 5, 3
• Amphotericin B deoxycholate 0.3-0.6 mg/kg daily with or without oral flucytosine (25 mg/kg four times daily) can be used as alternative therapy 5
• Recent evidence suggests fluconazole step-down therapy may be reasonable after initial echinocandin treatment for candidemia, though this requires careful monitoring 6
• Avoid empirical fluconazole for suspected invasive C. glabrata due to high resistance rates 5, 3

Monitoring for Echinocandin Resistance

• Prolonged echinocandin therapy can select for resistant C. glabrata mutants with FKS gene mutations 7, 3
• If recurrent candidemia occurs despite echinocandin therapy, consider resistance testing 7