What is the recommended treatment for Candida glabrata infections?

Treatment of Candida glabrata Infections

An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line treatment for Candida glabrata infections, particularly in critically ill patients or those with recent azole exposure. 1

First-Line Echinocandin Therapy

The Infectious Diseases Society of America guidelines strongly recommend echinocandins as initial therapy for C. glabrata due to this species' intrinsic reduced susceptibility to azoles and superior outcomes demonstrated in critically ill patients. 2, 1 The three echinocandins are equally acceptable options:

• Caspofungin: 70 mg loading dose, then 50 mg daily 2, 1
• Micafungin: 100 mg daily 2, 1
• Anidulafungin: 200 mg loading dose, then 100 mg daily 2, 1

All three echinocandins demonstrate excellent fungicidal activity against C. glabrata in vitro, including fluconazole-resistant strains. 3 Time-kill studies show these agents achieve fungicidal effects at 8-16× MIC concentrations, with prolonged post-antifungal effects that are markedly longer for anidulafungin and caspofungin compared to micafungin. 4

When Azole Therapy May Be Considered

Fluconazole can be used as initial therapy only in less critically ill patients without recent azole exposure, but this requires documented susceptibility testing confirming fluconazole susceptibility. 2, 1 The regimen is:

• Fluconazole: 800 mg loading dose, then 400 mg daily 2, 1

Critical caveat: Azole susceptibility testing is mandatory for all C. glabrata isolates from blood and sterile sites before considering azole therapy. 1 Do not use azoles empirically for C. glabrata without susceptibility data.

Step-Down to Oral Azole Therapy

Transition from intravenous echinocandin to oral fluconazole is reasonable after 5-7 days if all of the following criteria are met: 2, 1, 5

• Documented fluconazole susceptibility on testing
• Clinical stability achieved
• Negative repeat blood cultures documented
• Source control obtained

For fluconazole-susceptible isolates, use fluconazole 800 mg (12 mg/kg) daily after transition. 1 Recent data from 2025 demonstrates that fluconazole step-down therapy is safe and effective, with no significant difference in 30-day clinical failure rates compared to continued echinocandin therapy (9% vs 15%, p=0.58). 5

Alternative Therapies for Intolerance or Resistance

If echinocandins cannot be used due to intolerance, resistance, or limited availability: 2, 1

• Lipid formulation amphotericin B: 3-5 mg/kg daily 2, 1
• Amphotericin B deoxycholate: 0.5-1.0 mg/kg daily (less preferred due to toxicity) 2

Echinocandin susceptibility testing should be considered in patients with prior echinocandin exposure. 1

Essential Management Components Beyond Antifungals

Source control is critical: 2, 1

• Remove central venous catheters in non-neutropenic patients as early as possible 2, 1
• Remove or replace indwelling urinary catheters when feasible 1

Monitoring requirements: 1

• Perform daily or every other day follow-up blood cultures until clearance is documented 1
• Conduct dilated ophthalmologic examination within the first week after diagnosis 1

Treatment Duration

Continue therapy for 2 weeks after documented clearance of Candida from the bloodstream AND resolution of symptoms attributable to candidemia AND resolution of neutropenia. 2, 1 Deep tissue infections require longer treatment courses based on the specific site and clinical response. 1

Important Pitfalls to Avoid

Do not escalate echinocandin doses beyond standard regimens. Despite theoretical appeal, dose escalation studies demonstrate that higher caspofungin doses (up to 20 mg/kg daily in animal models) do not improve efficacy beyond standard dosing and may paradoxically decrease killing activity at very high concentrations. 6, 7 Standard human dosing regimens are predicted to achieve fungistatic effects in neutropenic hosts, but clinical dose escalation has not proven beneficial. 7

Do not use voriconazole as first-line therapy for C. glabrata. While voriconazole can be used when additional mold coverage is desired, it should not replace echinocandins for documented C. glabrata infections. 2 In candidemia trials, voriconazole showed only 33% success rates for C. glabrata infections. 8

Site-Specific Considerations for Cystitis

For fluconazole-susceptible C. glabrata cystitis specifically: 1

• Oral fluconazole: 200 mg daily for 2 weeks 1

For fluconazole-resistant C. glabrata cystitis: 1

• Amphotericin B deoxycholate: 0.3-0.6 mg/kg daily for 1-7 days, OR
• Oral flucytosine: 25 mg/kg four times daily for 7-10 days 1