What is the recommended treatment approach for a patient diagnosed with a Candida glabrata infection?

Treatment of Candida glabrata Infections

An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line therapy for invasive C. glabrata infections, and fluconazole should NOT be used as initial therapy due to intrinsic reduced susceptibility and high treatment failure rates. 1, 2

Initial Therapy Selection

Echinocandins as First-Line Treatment

• Echinocandins are explicitly preferred for C. glabrata infections with demonstrated fungicidal activity and success rates of approximately 75% in randomized trials 1, 2

• Specific dosing regimens include:

  • Caspofungin: 70 mg loading dose, then 50 mg daily 1
  • Micafungin: 100 mg daily 1
  • Anidulafungin: 200 mg loading dose, then 100 mg daily 1

• The three echinocandins are considered interchangeable in efficacy and can be selected based on availability and institutional preference 1

Why Fluconazole Should Be Avoided

• C. glabrata has intrinsic reduced susceptibility to azoles, making fluconazole frequently ineffective as initial therapy 1, 3, 2

• High-risk populations for C. glabrata (elderly patients, those with cancer, diabetes, or recent azole exposure) should NOT receive fluconazole as first-line therapy 1, 2

• European surveillance data shows 10.47% fluconazole resistance rates among C. glabrata isolates, with increasing resistance trends 4

Step-Down Therapy Considerations

Transition to Azoles

• Transition from an echinocandin to fluconazole or voriconazole is NOT recommended without confirmed susceptibility testing 1

• If susceptibility is confirmed, fluconazole step-down appears safe with no significant difference in 30-day clinical failure rates (9% vs 15%) compared to continued echinocandin therapy 5

• Voriconazole can be used as step-down oral therapy for voriconazole-susceptible C. glabrata (400 mg twice daily for 2 doses, then 200 mg twice daily) 1

Duration of Therapy

• Continue treatment for 2 weeks after documented clearance of Candida from bloodstream and resolution of symptoms for candidemia without metastatic complications 1

• Treatment duration typically ranges from 15-19 days depending on clinical response and source control 5

Alternative Therapies

Amphotericin B Formulations

• Amphotericin B deoxycholate (0.5-1.0 mg/kg daily) or liposomal amphotericin B (3-5 mg/kg daily) are alternatives if echinocandin intolerance or unavailability exists 1

• Amphotericin B with or without flucytosine (25 mg/kg four times daily) can be used for fluconazole-resistant strains 3

• European data shows high sensitivity of C. glabrata to amphotericin B, making it a viable empirical option 4

Site-Specific Treatment Approaches

Vulvovaginal Candidiasis

• Intravaginal boric acid 600 mg daily for 14 days is first-line therapy for C. glabrata vulvovaginal candidiasis, achieving 70% clinical and mycologic eradication rates 2, 6

• Boric acid must be compounded in gelatin capsules and administered at bedtime for optimal retention 6

• Alternative options if boric acid fails include:

  • Nystatin intravaginal suppositories (100,000 units daily) 6
  • Topical 17% flucytosine cream for 14 days 2, 6
  • Combination 17% flucytosine plus 3% amphotericin B cream daily for 14 days 6

Respiratory Colonization

• C. glabrata in sputum represents colonization, not infection, and does NOT require antifungal treatment in the absence of invasive disease 3

• Systemic/invasive candidiasis must be documented through positive blood cultures or tissue biopsy showing invasion before treatment 3

• Treating sputum colonization leads to unnecessary antifungal exposure, drug resistance development, and adverse effects 3

Critical Clinical Considerations

Source Control

• Intravenous catheter removal is strongly recommended for non-neutropenic patients with candidemia 1

• Source control was achieved in 43-58% of patients in recent cohorts and is essential for treatment success 5

Severity-Based Approach

• Patients with moderately severe to severe illness (hemodynamically unstable) should receive echinocandins regardless of azole exposure history 1

• Early initiation of effective antifungal therapy is critical, as delayed therapy correlates with increased mortality 1

Resistance Monitoring

• Increasing echinocandin resistance has been reported, particularly to anidulafungin (0.89% in European surveillance) 4

• Antifungal susceptibility testing is required to determine optimal therapeutic options, especially given rising azole resistance 4

• Prolonged azole exposure can select for resistant strains, and prophylactic fluconazole should be limited to minimize resistance emergence 2

Common Pitfalls to Avoid

• Never use empirical fluconazole for suspected C. glabrata without species identification and susceptibility confirmation, as this risks treatment failure and increased mortality 3, 2

• Do not transition to azole therapy without documented susceptibility, even if the patient is clinically stable 1

• Avoid treating respiratory colonization reflexively—evaluate for true invasive disease first 3

• For vulvovaginal infections, do not use boric acid empirically without culture confirmation of non-albicans species 6