What is the best treatment for Candida glabrata?

Treatment of Candida glabrata Infections

For invasive Candida glabrata infections including candidemia, an echinocandin (caspofungin, micafungin, or anidulafungin) is the strongly preferred first-line therapy due to this species' intrinsic reduced susceptibility to azole antifungals. 1, 2

Invasive/Systemic Infections (Candidemia, Deep Tissue)

First-Line Therapy

• Echinocandins are the mandatory first choice for all invasive C. glabrata infections 1, 2
• Dosing options include:
  • Caspofungin: 70 mg loading dose, then 50 mg daily 1
  • Micafungin: 100 mg daily 1, 3
  • Anidulafungin: 200 mg loading dose, then 100 mg daily 1

Treatment Duration and Monitoring

• Continue therapy for 14 days after documented clearance of Candida from bloodstream and complete resolution of symptoms 1, 2
• Remove central venous catheters as early as possible—this is critical for treatment success 1, 2
• Obtain daily or every-other-day follow-up blood cultures until clearance is documented 1

Step-Down Therapy Considerations

• Fluconazole step-down is NOT recommended without documented susceptibility testing confirming MIC ≤32 mcg/mL 1, 2
• If initial echinocandin therapy shows clinical improvement with negative follow-up cultures, continuing the echinocandin to completion is reasonable 1
• Recent evidence suggests fluconazole step-down may be safe in selected patients with documented susceptibility, but echinocandin continuation remains the conservative approach 4

Alternative Agents

• Amphotericin B deoxycholate 0.5-1.0 mg/kg daily is an alternative if echinocandins are unavailable or not tolerated 1, 2
• Voriconazole can be considered only as step-down therapy for voriconazole-susceptible isolates after initial echinocandin treatment 1

Urinary Tract Infections

Fluconazole-Susceptible C. glabrata

• Oral fluconazole 200 mg (3 mg/kg) daily for 14 days is appropriate for documented susceptible isolates 2

Fluconazole-Resistant C. glabrata

• Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days is the preferred treatment 1, 2
• Oral flucytosine 25 mg/kg four times daily for 7-10 days is an alternative 1, 2
• Amphotericin B bladder irrigation (50 mg/L sterile water daily for 5 days) can be used for refractory cystitis, though recurrence rates are high 1, 2

Essential Management Steps

• Remove indwelling bladder catheters whenever feasible—this is mandatory for treatment success 1, 2
• Do NOT use lipid formulations of amphotericin B for urinary tract infections due to poor urinary concentrations 1
• Echinocandins are not recommended for UTI due to poor urinary drug concentrations 1

Vulvovaginal Candidiasis

First-Line Therapy

• Intravaginal boric acid 600 mg in gelatin capsule daily for 14 days is the preferred treatment 2, 5
• This is especially effective when oral azoles have failed 2, 5

Alternative Options

• Nystatin intravaginal suppositories 100,000 units daily for 14 days 2, 5
• Topical 17% flucytosine cream combined with 3% amphotericin B cream daily for 14 days 5, 6
• Systemic micafungin combined with topical ciclopirox olamine has shown success in small case series 7

Critical Treatment Principles

• Complete the full 14-day course—shorter durations lead to treatment failure 2, 5
• Standard azole therapy (fluconazole, itraconazole) frequently fails due to intrinsic resistance 5, 7, 8
• Confirm diagnosis with vaginal culture, as C. glabrata doesn't form pseudohyphae on microscopy 5

Oropharyngeal Candidiasis

Azole-Refractory Disease

• Itraconazole solution 200 mg once daily OR posaconazole suspension 400 mg twice daily for 3 days, then 400 mg daily for up to 28 days 2
• Voriconazole 200 mg twice daily is an alternative 2
• Intravenous echinocandin for severe refractory cases 2

Critical Pitfalls to Avoid

Never Assume Fluconazole Susceptibility

• C. glabrata has intrinsic reduced azole susceptibility—always obtain susceptibility testing before using azoles 1, 2, 8
• Cross-resistance between azoles is common 9

Device Removal is Mandatory

• Failure to remove infected catheters, lines, or stents is a primary cause of treatment failure 1, 2

Don't Treat Respiratory Colonization

• C. glabrata in sputum represents colonization, not infection 2
• True Candida pneumonia is extremely rare and requires tissue biopsy showing invasion 2
• Obtain blood cultures or tissue diagnosis before initiating antifungal therapy 2

Dosing Considerations

• Higher echinocandin doses may be required in neutropenic patients to achieve fungicidal rather than fungistatic effects 10
• Patients weighing >120 kg may require dose adjustments due to decreased drug exposure 9