Treatment of Candida glabrata Infections
An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line treatment for Candida glabrata infections. 1
Initial Therapy
For invasive C. glabrata infections, start with an echinocandin at standard dosing:
- 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 2016 IDSA guidelines provide strong, high-quality evidence supporting echinocandins as initial therapy for candidemia, with specific preference for C. glabrata due to its reduced azole susceptibility 1. This represents an upgrade from the 2009 guidelines, which gave this recommendation a B-III evidence rating 1.
Why Echinocandins Are Preferred
C. glabrata has intrinsically reduced susceptibility to fluconazole, making azoles unreliable as first-line agents 1. Clinical trial data demonstrate excellent efficacy: micafungin achieved 93.8% success rates for C. glabrata candidemia 2, and pooled trial data showed 73.5% clinical cure rates 3.
Alternative Agents
Lipid formulation amphotericin B (LFAmB) at 3-5 mg/kg daily is an effective but less attractive alternative if echinocandins cannot be used 1. Amphotericin B deoxycholate (0.5-1.0 mg/kg daily) can be used if there is intolerance to or limited availability of other antifungals 1.
Transition to Azole Therapy
Do not transition to fluconazole or voriconazole without documented susceptibility testing 1. The 2016 guidelines recommend testing for azole susceptibility on all bloodstream and clinically relevant Candida isolates 1.
If the patient was initially started on an azole (fluconazole or voriconazole), is clinically improved, and follow-up cultures are negative, continuing the azole to completion is reasonable 1. However, for C. glabrata specifically, transition to higher-dose fluconazole (800 mg or 12 mg/kg daily) may be considered only after susceptibility is confirmed 1.
Voriconazole can be used as step-down oral therapy for voriconazole-susceptible C. glabrata at 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily 1. However, voriconazole offers little advantage over fluconazole and should be reserved for documented susceptible isolates 1.
Duration of Therapy
Treat for 2 weeks after documented clearance of Candida from the bloodstream and resolution of symptoms 1. In neutropenic patients, continue until resolution of neutropenia as well 1.
Catheter Management
Remove intravenous catheters in nonneutropenic patients with candidemia (strongly recommended) 1. In neutropenic patients, catheter removal should be considered 1. Failure to remove central venous catheters is independently associated with 28-day mortality 3.
Critical Considerations for Neutropenic Patients
Neutropenic hosts may require higher echinocandin doses to achieve fungicidal activity. Experimental data suggest that standard human dosing regimens may only achieve fungistatic effects in neutropenic patients 4. Consider combination therapy with liposomal amphotericin B plus an echinocandin in severely immunosuppressed patients, as this approach achieved complete clearance in animal models where monotherapy failed 5.
Common Pitfalls
- Assuming fluconazole will work: C. glabrata has reduced azole susceptibility; always start with an echinocandin unless susceptibility is documented 1
- Failing to remove catheters: This is independently associated with mortality and treatment failure 3
- Undertreating neutropenic patients: Standard echinocandin doses may be insufficient; consider higher doses or combination therapy 4, 5
- Switching to azoles too early: Only transition after documented susceptibility testing and clinical stability 1