What is the recommended treatment for Candida glabrata infection?

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 preference for echinocandins stems from C. glabrata's intrinsic reduced susceptibility to azoles and superior outcomes in critically ill patients. 1 The recommended dosing regimens are:

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

All three echinocandins demonstrate comparable efficacy against C. glabrata, with clinical cure rates of approximately 73% in head-to-head comparisons. 3 Pharmacodynamic studies confirm that standard dosing achieves therapeutic targets even against isolates with fks mutations, though micafungin and caspofungin breakpoints may need adjustment for mutant strains. 4

Alternative Therapy: Fluconazole

Fluconazole may be considered only in less critically ill patients without recent azole exposure, but this requires mandatory susceptibility testing. 1

• Dosing: 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily 2, 1
• Critical caveat: Fluconazole should only be used if susceptibility is confirmed, as C. glabrata has intrinsic reduced susceptibility to azoles 1
• A fluconazole dose-to-MIC ratio >12.5 is associated with significantly higher response rates (49% vs 20% when ratio ≤12.5) 5

Step-Down Therapy Strategy

Transition from IV echinocandin to oral fluconazole requires both documented susceptibility AND clinical stability. 1, 6

• Switch to fluconazole 800 mg (12 mg/kg) daily after 5-7 days if the patient is clinically stable with negative repeat cultures 1
• Recent data from 2025 demonstrates that fluconazole step-down therapy results in similar 30-day clinical failure rates compared to continued echinocandin therapy (9% vs 15%, p=0.58) 6
• For voriconazole-susceptible isolates, voriconazole 200-300 mg (3-4 mg/kg) twice daily is an alternative step-down option 1

Amphotericin B as Salvage Therapy

When echinocandins and azoles are not options due to resistance or intolerance:

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

Essential Management Components

Mandatory Testing

• Azole susceptibility testing is mandatory for all C. glabrata isolates from blood and sterile sites 1
• Echinocandin susceptibility testing should be considered in patients with prior echinocandin exposure 1

Source Control

• Remove central venous catheters in non-neutropenic patients with candidemia 2, 1
• Failure to remove catheters is independently associated with 28-day mortality 3
• Remove or replace indwelling urinary catheters when feasible 2, 1

Treatment Duration

• Continue therapy for 2 weeks after documented clearance from bloodstream and resolution of symptoms 2, 1
• Perform daily or every-other-day follow-up blood cultures until clearance is documented 1
• Deep tissue infections require longer courses based on site and response 1

Monitoring

• Conduct a dilated ophthalmologic examination within the first week after diagnosis of candidemia 1

Site-Specific Considerations

Cystitis (Fluconazole-Susceptible)

• Oral fluconazole 200 mg daily for 2 weeks 2, 1
• Remove indwelling bladder catheter if feasible 2, 1

Cystitis (Fluconazole-Resistant)

• Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days 2, 1
• OR oral flucytosine 25 mg/kg four times daily for 7-10 days 2, 1
• Amphotericin B bladder irrigation (50 mg/L sterile water daily for 5 days) may be useful 2

Pyelonephritis (Fluconazole-Susceptible)

• Oral fluconazole 200-400 mg (3-6 mg/kg) daily for 2 weeks 2
• Eliminate urinary tract obstruction 2

Surgical Site Infections

• Echinocandin therapy as above (caspofungin, micafungin, or anidulafungin) 7
• Surgical debridement of infected tissue is strongly recommended 7
• Continue therapy until complete resolution of all signs and symptoms 7
• These infections typically require weeks rather than the 2-week minimum for uncomplicated candidemia 7

Common Pitfalls to Avoid

• Do not use fluconazole empirically without susceptibility testing, as C. glabrata has intrinsic reduced susceptibility 1
• Do not delay catheter removal in non-neutropenic patients, as this independently predicts mortality 3
• Do not transition to oral therapy prematurely—ensure clinical stability and negative repeat cultures first 1, 6
• Do not underdose fluconazole if used—a dose-to-MIC ratio >12.5 is critical for response 5