What is the preferred treatment for Candida glabrata infection?

Treatment of Candida glabrata Infections

An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line treatment for invasive Candida glabrata infections, including candidemia. 1, 2, 3

Initial Antifungal Selection

Echinocandins as First-Line Therapy

• Echinocandins are explicitly preferred for C. glabrata due to this species' intrinsic reduced susceptibility to azoles and demonstrated fungicidal activity. 1, 2, 3

• The three echinocandins are considered interchangeable in efficacy with approximately 75% success rates in randomized trials: 2, 3

  • Caspofungin: 70 mg IV loading dose, then 50 mg IV daily 1, 2, 3
  • Micafungin: 100 mg IV daily 1, 2, 3
  • Anidulafungin: 200 mg IV loading dose, then 100 mg IV daily 1, 2, 3

• Echinocandins are particularly critical for moderately severe to severely ill patients (hemodynamically unstable), those with recent azole exposure, elderly patients, patients with underlying malignancy, and diabetic patients. 1, 2

When Fluconazole May Be Considered

• High-dose fluconazole (800 mg loading dose, then 400 mg daily or 12 mg/kg daily) may be considered only for less critically ill patients without recent azole exposure, but this requires documented fluconazole susceptibility testing. 1, 3

• Do not use fluconazole as initial therapy without confirmed susceptibility—this risks treatment failure and increased mortality. 2, 3

• Recent research suggests that when appropriately selected, fluconazole may achieve similar outcomes to echinocandins in non-critically ill patients with susceptible isolates, though patients receiving fluconazole are frequently switched to other agents. 4, 5

Mandatory Susceptibility Testing

• Azole susceptibility testing is mandatory for all C. glabrata isolates from blood and sterile sites before considering any azole therapy. 1, 3

• Echinocandin susceptibility testing should be performed in patients with prior echinocandin exposure, as emerging resistance has been documented (approximately 9-11% of fluconazole-resistant isolates show echinocandin resistance). 3, 6

Step-Down Therapy

• Transition from an echinocandin to fluconazole or voriconazole is NOT recommended without confirmed susceptibility testing. 1, 2

• After 5-7 days of echinocandin therapy, step-down to oral fluconazole 800 mg (12 mg/kg) daily is permissible only if: 3

  • The patient is clinically stable
  • Repeat blood cultures are negative
  • Susceptibility testing confirms fluconazole MIC <32 µg/mL

• For voriconazole-susceptible C. glabrata, voriconazole 200-300 mg (3-4 mg/kg) twice daily can be used as step-down oral therapy. 1, 3

• Recent data support fluconazole step-down as safe and reasonable when appropriately selected, with no significant difference in 30-day clinical failure rates. 7

Alternative Therapies

When echinocandin intolerance or unavailability exists:

• Amphotericin B deoxycholate: 0.5-1.0 mg/kg IV daily 1, 2
• Liposomal amphotericin B: 3-5 mg/kg IV daily 1, 2, 3

Essential Source Control Measures

• Intravenous catheter removal is strongly recommended for all non-neutropenic patients with candidemia—failure to remove catheters is the most frequent cause of treatment failure and recurrence. 1, 2, 3, 8

• Remove or replace any indwelling urinary catheter when urinary tract involvement is present. 3, 8

Treatment Duration and Monitoring

• Continue antifungal therapy for at least 2 weeks after documented clearance of Candida from bloodstream and complete resolution of symptoms for candidemia without metastatic complications. 1, 2, 3, 8

• Obtain daily or every-other-day follow-up blood cultures until clearance is documented. 3, 8

• Perform a dilated ophthalmologic examination within the first week after diagnosis to exclude endophthalmitis. 3, 8

• Deep tissue infections require longer treatment courses based on site and clinical response. 3

Site-Specific Considerations

Urinary Tract Infections

• Echinocandins achieve minimal urinary concentrations and are NOT recommended for urinary infections. 3, 8

• For fluconazole-susceptible C. glabrata cystitis: oral fluconazole 200 mg daily for 2 weeks. 3

• For fluconazole-resistant C. glabrata: amphotericin B deoxycholate 0.3-0.6 mg/kg IV daily for 1-7 days or oral flucytosine 25 mg/kg four times daily for 7-10 days. 3, 8

• Lipid amphotericin B formulations should be avoided in urinary tract infections due to inadequate urinary drug concentrations. 8

Endocardial or CNS Involvement

• Use amphotericin B for suspected endocardial or CNS infection due to superior fungicidal activity and CNS penetration. 8

Critical Pitfalls to Avoid

• Do not delay antifungal initiation—early therapy is critical, as delayed treatment correlates with increased mortality. 2

• Do not use fluconazole without documented susceptibility—C. glabrata has high rates of reduced azole susceptibility. 1, 2

• Do not use echinocandins for urinary tract infections—inadequate urinary drug levels render them ineffective. 3, 8

• Do not continue therapy without removing implicated catheters—this is the most common cause of treatment failure. 8

• Do not assume clinical outcomes based solely on in vitro susceptibility—approximately 9-11% of fluconazole-resistant C. glabrata isolates now show echinocandin resistance, representing an emerging threat. 6

• When using fluconazole for susceptible isolates, ensure a dose:MIC ratio >12.5 to optimize response rates. 5