Treatment of Candida glabrata Infections
Echinocandins are the first-line treatment for Candida glabrata infections due to this species' intrinsic reduced susceptibility to fluconazole. 1
First-Line Treatment Options
Echinocandins
- Caspofungin: Loading dose 70 mg, then 50 mg daily 2, 1
- Micafungin: 100 mg daily 2, 1
- Anidulafungin: Loading dose 200 mg, then 100 mg daily 2, 1
Echinocandins are strongly preferred for C. glabrata infections because they demonstrate superior efficacy compared to azoles. The Infectious Diseases Society of America (IDSA) guidelines specifically recommend echinocandins as initial therapy for C. glabrata infections 2.
Clinical evidence supports this recommendation, with studies showing clinical cure rates of 73.5% for micafungin in patients with C. glabrata infections 3. However, pharmacodynamic studies suggest that standard echinocandin dosing may only achieve fungistatic (rather than fungicidal) effects in neutropenic hosts, which may be a consideration in severely immunocompromised patients 4.
Alternative Treatment Options
When echinocandins cannot be used or are contraindicated, the following alternatives may be considered:
Lipid Formulation of Amphotericin B (LFAmB)
- Dosage: 3-5 mg/kg daily 2, 1
- Less attractive than echinocandins due to potential toxicity concerns, but effective 2
For Urinary Tract Infections (Specific Scenarios)
- Fluconazole-resistant C. glabrata cystitis:
- Amphotericin B deoxycholate (0.3-0.6 mg/kg daily for 1-7 days) or
- Oral flucytosine (25 mg/kg 4 times daily for 7-10 days) 1
- Fluconazole-resistant C. glabrata pyelonephritis:
- Amphotericin B deoxycholate with or without oral flucytosine 1
- Bladder irrigation: Amphotericin B deoxycholate (50 mg/L sterile water daily for 5 days) for cystitis 1
Transitioning Between Antifungals
- Do not transition to fluconazole or voriconazole without confirmation of isolate susceptibility 2, 1
- For patients who have initially received fluconazole or voriconazole, are clinically improved, and have negative follow-up cultures, continuing the azole to completion may be reasonable 2, 1
- Transition from an echinocandin to higher-dose fluconazole (800 mg/12 mg/kg daily) or voriconazole (200-300 mg/3-4 mg/kg twice daily) should only be considered for patients with susceptible isolates 2
Susceptibility Testing and Monitoring
- Testing for azole susceptibility is strongly recommended for all bloodstream and clinically relevant C. glabrata isolates 2, 1
- Testing for echinocandin susceptibility should be considered in patients who have had prior treatment with an echinocandin 2, 1
- Be vigilant for rapid emergence of echinocandin resistance, which can develop after as little as 12 days of treatment 5
Duration of Treatment and Management
- Continue treatment for at least 2 weeks after:
- Follow-up blood cultures should be performed every day or every other day to establish clearance of candidemia 2
- Intravenous catheter removal is strongly recommended for non-neutropenic patients with candidemia 2, 1
Important Clinical Considerations
- C. glabrata has intrinsically reduced susceptibility to fluconazole, making echinocandins the preferred choice
- Higher dosages of echinocandins may be required to achieve fungicidal effects in neutropenic hosts 4
- Drug-specific MIC breakpoints may need to be considered for optimal treatment selection 6
- Monitor for potential adverse effects, including elevated liver enzymes and histamine-mediated reactions with echinocandins, and nephrotoxicity with amphotericin B formulations 1
The treatment of C. glabrata infections requires careful consideration of antifungal susceptibility patterns and patient-specific factors. Echinocandins remain the cornerstone of therapy, with alternative options available for specific clinical scenarios or when echinocandins cannot be used.