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
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 preference for echinocandins over fluconazole stems from C. glabrata's intrinsic reduced susceptibility to azoles and the superior outcomes demonstrated in critically ill patients. 1
Alternative: Fluconazole (Selected Cases Only)
Fluconazole 800 mg loading dose, then 400 mg daily may be considered for less critically ill patients without recent azole exposure, but only if susceptibility testing confirms fluconazole susceptibility. 1 This is a critical caveat—do not use fluconazole empirically for C. glabrata without documented susceptibility. 1
Other Alternatives
- Lipid formulation amphotericin B: 3-5 mg/kg daily if intolerance or resistance to other agents 1
- Amphotericin B deoxycholate: 0.5-1.0 mg/kg daily (less preferred due to toxicity) 1
Susceptibility 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
Step-Down Therapy
Transition from echinocandin to oral azole therapy requires documented susceptibility and clinical stability. 1
- For fluconazole-susceptible isolates: transition to fluconazole 800 mg (12 mg/kg) daily after 5-7 days if clinically stable with negative repeat cultures 1
- For voriconazole-susceptible isolates: voriconazole 200-300 mg (3-4 mg/kg) twice daily is an option 1
- Do not transition to azole therapy without confirmed susceptibility testing 1
Recent evidence suggests fluconazole step-down is safe when appropriately selected, with no significant difference in 30-day clinical failure rates compared to continued echinocandin therapy. 2
Site-Specific Considerations
Urinary Tract Infections
- Fluconazole-susceptible C. glabrata cystitis: Oral fluconazole 200 mg daily for 2 weeks 1
- 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
- Pyelonephritis: Same regimens with mandatory elimination of urinary obstruction 1
- Remove or replace indwelling catheters when feasible 1
Candidemia
- Duration: Continue therapy for 2 weeks after documented clearance from bloodstream and resolution of symptoms 1
- Follow-up cultures: Perform daily or every other day until clearance documented 1
- Catheter management: Strongly recommended to remove central venous catheters in non-neutropenic patients 1
- Ophthalmologic examination: Dilated exam within first week after diagnosis 1
Common Pitfalls
Dosing Considerations
The dose:MIC ratio matters for fluconazole—ratios >12.5 are associated with significantly higher response rates (49% vs 20% for ratios ≤12.5). 3 This supports using the higher 800 mg daily dose when fluconazole is selected.
Paradoxical Effect
Echinocandin dose escalation beyond standard doses does not improve efficacy and may paradoxically decrease killing activity at very high concentrations in vitro. 4 Standard dosing (not dose escalation) is appropriate. 4, 5
Species Misidentification Risk
C. glabrata is the second most common Candida species causing invasive disease, accounting for approximately 15% of candidemia cases. 6 Ensure proper species identification before assuming azole susceptibility.
Neutropenic Patients
In profoundly neutropenic hosts, echinocandins may only achieve fungistatic rather than fungicidal effects at standard doses, though higher doses have not proven more effective clinically. 4, 5 Maintain standard dosing but ensure adequate treatment duration.