What is the recommended antifungal regimen and duration for a confirmed Candida glabrata infection, including first‑line options and alternatives based on susceptibility and patient severity?

Treatment of Candida glabrata Infections

An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line treatment for Candida glabrata infections, particularly for moderately severe to severe illness, recent azole exposure, or when azole resistance is suspected. 1, 2

First-Line Therapy: Echinocandins

The echinocandins are strongly preferred because C. glabrata demonstrates intrinsic reduced susceptibility to azoles and these agents provide superior fungicidal activity 1, 2. The dosing regimens are:

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

When Echinocandins Are Critical

Echinocandins should be used preferentially in the following scenarios:

• Moderately severe to severely ill patients (hemodynamically unstable) 1
• Recent azole exposure within the past 3 months 1
• Critically ill patients in intensive care settings 1
• Patients at high risk for fluconazole-resistant Candida species 1

Alternative Therapy: High-Dose Fluconazole (With Major Caveats)

Fluconazole may only be considered for less critically ill patients without recent azole exposure, and ONLY after documented susceptibility testing confirms fluconazole susceptibility. 1, 2

• Dosing: 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily 1, 2
• Mandatory requirement: Azole susceptibility testing must be performed on all C. glabrata blood and sterile site isolates before initiating or continuing azole therapy 1, 2
• Critical pitfall: Approximately 10-15% of fluconazole-resistant C. glabrata isolates now demonstrate co-resistance to echinocandins, making empiric fluconazole use increasingly risky 3, 4

Step-Down Therapy Strategy

Transition from echinocandin to oral fluconazole is NOT recommended without confirmed susceptibility results. 1, 2

Criteria for Safe Step-Down (All Must Be Met):

• Minimum 5-7 days of echinocandin therapy completed 2, 5
• Patient is clinically stable with improving symptoms 1, 5
• Repeat blood cultures are negative (documented clearance) 1, 5
• Fluconazole MIC is ≤32 µg/mL (susceptible) 2
• No endovascular complications present 5

If these criteria are met, transition to fluconazole 800 mg (12 mg/kg) daily or voriconazole 200-300 mg (3-4 mg/kg) twice daily for voriconazole-susceptible isolates 2, 5. Recent data from 2025 supports that fluconazole step-down is safe and effective when appropriately selected, with no difference in 30-day clinical failure rates compared to continued echinocandin therapy 5.

Second-Line Alternatives (When Echinocandins Unavailable or Intolerant)

Amphotericin B formulations provide effective alternatives:

• Liposomal amphotericin B (LFAmB): 3-5 mg/kg IV daily (preferred formulation due to lower toxicity) 1, 2
• Amphotericin B deoxycholate: 0.5-1.0 mg/kg IV daily (higher toxicity risk) 1

LFAmB is effective but considered less attractive than echinocandins for C. glabrata 1. Combination therapy with liposomal amphotericin B plus an echinocandin has shown enhanced efficacy in animal models but lacks robust human data 6.

Essential Source Control Measures

Central venous catheter removal is strongly recommended for all non-neutropenic patients with C. glabrata candidemia. 1, 2

• Failure to remove the catheter is the most frequent cause of treatment failure and recurrence 2
• Catheter removal should occur as early as possible when the source is presumed to be catheter-related and removal can be performed safely 1
• For neutropenic patients, catheter removal should be considered on an individual basis 1

Treatment Duration and Monitoring

Continue antifungal therapy for at least 2 weeks after documented clearance of Candida from the bloodstream AND complete resolution of symptoms. 1, 2

Monitoring Requirements:

• Perform follow-up blood cultures 48-72 hours after initiating therapy, then every other day until clearance is documented 1, 2
• Conduct dilated ophthalmologic examination within the first week after diagnosis to exclude endophthalmitis 1, 2
• For neutropenic patients, continue therapy until resolution of neutropenia in addition to the 2-week post-clearance period 1

Special Populations

Pregnancy

Amphotericin B deoxycholate is the treatment of choice for pregnant women with C. glabrata infections due to its established safety profile in pregnancy 1, 7.

Neutropenic Patients

• Echinocandins remain first-line 1
• Catheter removal is controversial and should be individualized 1
• Treatment duration extends until neutropenia resolves 1

Common Pitfalls to Avoid

Critical errors that compromise outcomes:

• Using fluconazole empirically without susceptibility data in C. glabrata infections 1, 2, 4
• Failing to remove central venous catheters in non-neutropenic patients 1, 2
• Stepping down to azole therapy before confirming susceptibility and clinical stability 1
• Inadequate treatment duration (stopping before 2 weeks post-clearance) 1, 2
• Not performing follow-up blood cultures to document clearance 1, 2

Risk factors that predict fluconazole-resistant C. glabrata include: prior fluconazole use (12-fold increased risk), diabetes (10-fold increased risk), and presence of central venous catheter 4. When these risk factors are present, empiric echinocandin therapy is even more critical 1, 4.