What is the recommended treatment for Candida glabrata infection?

Treatment for Candida glabrata Infection

An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line treatment for Candida glabrata infections, particularly in critically ill patients, those with recent azole exposure, or when invasive disease is present. 1, 2

First-Line Therapy: Echinocandins

All major guidelines consistently recommend echinocandins as initial therapy for C. glabrata due to this species' intrinsic reduced susceptibility to azoles and the superior fungicidal activity of echinocandins. 3, 1

Dosing Regimens

• 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

All three echinocandins demonstrate approximately 75% success rates in randomized trials and are considered interchangeable based on availability and institutional preference. 2

Mandatory Patient Populations for Echinocandin Use

Echinocandins must be used preferentially in the following clinical scenarios:

• Hemodynamically unstable or severely ill patients (moderate to severe disease) 1, 2
• Recent azole exposure within the past 3 months 1
• Critically ill patients in intensive care settings 1
• Elderly patients, those with underlying malignancy, or diabetic patients 2
• Any patient with suspected or confirmed invasive candidiasis/candidemia 1, 2

Source Control Measures

Central venous catheter removal is strongly recommended and should occur as early as possible in all non-neutropenic patients with C. glabrata candidemia. 1, 4 Failure to remove catheters is the most frequent cause of treatment failure and recurrence. 1

Alternative Therapy: High-Dose Fluconazole (Use With Extreme Caution)

Fluconazole may ONLY be considered for less critically ill patients without recent azole exposure, and ONLY after documented susceptibility testing confirms fluconazole susceptibility (MIC ≤32 μg/ml). 1, 2

Critical Fluconazole Considerations

• Dosing: 800 mg (≈12 mg/kg) loading dose, then 400 mg (≈6 mg/kg) daily 1, 2
• Azole susceptibility testing is mandatory for all C. glabrata blood and sterile-site isolates before initiating any azole therapy 1
• Do NOT use fluconazole 150 mg as initial therapy—this dose is inadequate and associated with high treatment failure rates 2
• Recent research suggests fluconazole may be reasonable in selected patients when susceptibility is confirmed, though echinocandins remain preferred 5

Step-Down Therapy Criteria

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

Requirements for Safe Step-Down (All Must Be Met)

• Minimum 5-7 days of echinocandin therapy completed 1
• Patient clinically stable with improving symptoms 1
• Repeat blood cultures negative (documented clearance) 1
• Documented azole susceptibility confirmed by laboratory testing 1

Step-Down Options When Criteria Met

• Fluconazole: 800 mg (≈12 mg/kg) daily for fluconazole-susceptible isolates (MIC ≤32 μg/ml) 1
• Voriconazole: 200-300 mg (≈3-4 mg/kg) twice daily for voriconazole-susceptible isolates 1, 6

Recent data from 2025 supports fluconazole step-down as safe and reasonable when appropriately selected, with no significant difference in 30-day clinical failure rates compared to continued echinocandin therapy. 7

Second-Line Alternatives (When Echinocandins Unavailable or Intolerant)

• Liposomal amphotericin B: 3-5 mg/kg IV daily (preferred formulation due to lower toxicity) 1, 4
• Amphotericin B deoxycholate: 0.5-1.0 mg/kg IV daily (higher toxicity risk, less preferred) 1, 2
• Amphotericin B deoxycholate is the treatment of choice for pregnant women due to established safety profile 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. 3, 1

Essential Monitoring Parameters

• Perform follow-up blood cultures every 48-72 hours after therapy initiation, then every other day until clearance is documented 1, 4
• Conduct dilated ophthalmologic examination within the first week after diagnosis to exclude endophthalmitis 1, 4
• For neutropenic patients, continue therapy until neutropenia resolves in addition to the 2-week post-clearance period 1

Site-Specific Considerations

Urinary Tract Infections

• For fluconazole-susceptible C. glabrata cystitis: Oral fluconazole 200 mg daily for 2 weeks 1
• For fluconazole-resistant C. glabrata: 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
• Micafungin has shown success in case reports for C. glabrata urinary tract infections, though data are limited 8
• Remove or replace indwelling urinary catheters when feasible 1

Deep Tissue Infections

Voriconazole demonstrated favorable responses in deep tissue Candida infections including intra-abdominal infections (4/7 patients), kidney/bladder wall infections (5/6 patients), and deep tissue abscesses (3/3 patients), though echinocandins remain first-line. 6

Critical Pitfalls to Avoid

• Using fluconazole empirically without susceptibility data leads to treatment failure and increased mortality 1, 2
• Failing to remove central venous catheters in non-neutropenic patients increases risk of persistent infection 1
• Stepping down to azole therapy before confirming susceptibility and clinical stability compromises outcomes 1
• Inadequate treatment duration (stopping before 2 weeks post-clearance) results in higher relapse rates 1
• Not performing follow-up blood cultures to document clearance impedes assessment of therapeutic success 1
• Dose escalation of echinocandins (beyond standard dosing) does not improve efficacy and should not be routinely attempted 9

Emerging Resistance Concerns

Echinocandin resistance in C. glabrata is emerging, particularly among fluconazole-resistant isolates. Among fluconazole-resistant C. glabrata bloodstream isolates, 8-11% demonstrate resistance to one or more echinocandins, representing a significant increase from 0% in 2001-2004. 10 All echinocandin-resistant strains contain acquired mutations in fks1 or fks2 genes. 10 Consider echinocandin susceptibility testing in patients with prior echinocandin exposure or treatment failure. 1