Treatment of Candida glabrata Infections
For Candida glabrata infections, an echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line therapy, with lipid formulation amphotericin B as an alternative if echinocandins are not available or tolerated. 1
Initial Therapy
Echinocandin Regimens (Preferred)
The Infectious Diseases Society of America strongly recommends echinocandins as first-line therapy for C. glabrata infections 1:
- Caspofungin: Loading dose 70 mg, then 50 mg daily 1
- Micafungin: 100 mg daily 1
- Anidulafungin: Loading dose 200 mg, then 100 mg daily 1
Echinocandins are particularly favored for moderately severe to severe illness, recent azole exposure, or high risk of C. glabrata infection (elderly patients, cancer patients, diabetics) 1. This preference stems from C. glabrata's reduced susceptibility to azoles in vitro and the fungicidal activity of echinocandins 1.
Alternative Therapy
Lipid formulation amphotericin B (LFAmB) at 3-5 mg/kg daily is an effective but less attractive alternative when echinocandins cannot be used due to intolerance, limited availability, or resistance 1.
Critical Management Considerations
Azole Therapy Restrictions
Do not transition to fluconazole or voriconazole without documented susceptibility testing 1. This is a crucial pitfall to avoid, as approximately 9.7% of fluconazole-resistant C. glabrata isolates also demonstrate echinocandin resistance 2.
However, if a patient was already receiving fluconazole or voriconazole, is clinically improved, and has negative follow-up cultures, continuing the azole to completion of therapy is reasonable 1.
Susceptibility Testing
Perform azole susceptibility testing on all C. glabrata bloodstream and clinically relevant isolates 1. Consider echinocandin susceptibility testing in patients with prior echinocandin exposure or those infected with C. glabrata 1. This is particularly important given emerging coresistance patterns, with 11.1% of fluconazole-resistant isolates showing resistance to one or more echinocandins 2.
Step-Down Therapy
For C. glabrata specifically, transition to higher-dose fluconazole (800 mg or 12 mg/kg daily) or voriconazole (200-300 mg or 3-4 mg/kg twice daily) should only occur with documented susceptibility 1. The typical 5-7 day transition window used for C. albicans does not apply without susceptibility confirmation 1.
Duration and Adjunctive Measures
Treat for 2 weeks after documented clearance of Candida from the bloodstream and resolution of symptoms 1. In neutropenic patients, also ensure resolution of neutropenia before discontinuing therapy 1.
Strongly consider intravenous catheter removal in nonneutropenic patients 1. Failure to remove central venous catheters is independently associated with increased 28-day mortality 3.
Special Populations
Neutropenic Patients
Higher echinocandin doses may be required in neutropenic hosts to achieve fungicidal rather than fungistatic effects 4. Standard human dosing regimens are predicted to result in fungistatic activity in neutropenic patients, though clinical data supporting routine dose escalation remain limited 4.
Pediatric Patients
The same therapeutic approach applies to children with attention to weight-based dosing adjustments 1.
Emerging Resistance Concerns
Coresistance to both azoles and echinocandins in C. glabrata has emerged over time, with no echinocandin-resistant strains detected among fluconazole-resistant isolates in 2001-2004, but 11.1% showing this pattern by 2006-2010 2. All echinocandin-resistant isolates contained acquired mutations in fks1 or fks2 genes 2. This underscores the importance of susceptibility testing and avoiding empiric azole therapy in C. glabrata infections.