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

Treatment of Candida glabrata Infection

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

Initial Therapy Selection

First-Line: Echinocandins

• 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 echinocandin class is strongly preferred for C. glabrata due to this species' reduced susceptibility to azoles and the superior outcomes demonstrated with echinocandins. 1

Alternative: Lipid Formulation Amphotericin B

• LFAmB: 3-5 mg/kg daily is an effective but less attractive alternative if echinocandins cannot be used due to intolerance, limited availability, or resistance 1

Critical Caveat About Azoles

Do NOT transition to fluconazole or voriconazole without documented susceptibility testing. 1 C. glabrata exhibits intrinsic reduced susceptibility to fluconazole, making empiric azole therapy inappropriate. 1

When Azole Step-Down May Be Considered

If a patient was initially started on an echinocandin and meets ALL of the following criteria, azole continuation may be reasonable:

• Clinical improvement is documented 1
• Follow-up blood cultures are negative 1
• Susceptibility testing confirms fluconazole-susceptible isolate 1
• Patient is clinically stable 1

For susceptible isolates, transition options include:

• High-dose fluconazole: 800 mg (12 mg/kg) daily 1
• Voriconazole: 200-300 mg (3-4 mg/kg) twice daily 1

Recent data suggests fluconazole step-down appears safe in selected C. glabrata candidemia cases when susceptibility is confirmed. 2

Essential Adjunctive Measures

Catheter Management

• Remove central venous catheters in all nonneutropenic patients with candidemia 1
• Catheter removal is strongly recommended and impacts mortality 3, 4

Susceptibility Testing

• Mandatory azole susceptibility testing for all C. glabrata bloodstream isolates 1
• Consider echinocandin susceptibility testing in patients with prior echinocandin exposure 1

Monitoring Requirements

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

Duration of Therapy

Treat for 2 weeks after documented clearance of Candida from the bloodstream AND resolution of attributable symptoms. 1

Special Populations

Neutropenic Patients

• Echinocandins remain preferred 1
• Continue therapy until resolution of neutropenia in addition to the standard 2-week post-clearance period 1

Critically Ill or Moderately Severe Illness

• Echinocandins are strongly favored over azoles 1
• Higher severity of illness independently predicts lower cure rates and increased mortality 3

Patients with Recent Azole Exposure

• Echinocandins are preferred due to risk of azole resistance 1

Common Pitfalls to Avoid

1. Using fluconazole empirically for C. glabrata: This species has reduced azole susceptibility; always start with an echinocandin 1, 4

2. Failing to remove catheters: Catheter retention is independently associated with treatment failure and mortality 3

3. Switching to azoles without susceptibility data: Transition should only occur after confirming susceptibility 1

4. Inadequate treatment duration: Must continue for 2 weeks AFTER documented clearance, not from initiation 1

5. Using standard fluconazole doses: If azole therapy is appropriate based on susceptibility, use high-dose fluconazole (800 mg daily), not standard doses 1

Dosing Considerations

While standard micafungin 100 mg daily is effective for C. glabrata, pharmacodynamic studies suggest higher doses may be needed for fungicidal activity in neutropenic hosts, though clinical significance remains unclear. 5 The 100 mg daily dose remains the accepted standard based on clinical trial data. 6, 3