Treatment of Candida glabrata Infections
Echinocandins are the first-line treatment for Candida glabrata infections due to their superior efficacy compared to azoles. 1
First-Line Treatment: Echinocandins
Echinocandins are strongly recommended as initial therapy for C. glabrata infections:
- Caspofungin: Loading dose of 70 mg, then 50 mg daily
- Micafungin: 100 mg daily
- Anidulafungin: Loading dose of 200 mg, then 100 mg daily 1
These agents have demonstrated excellent activity against C. glabrata, including isolates that are resistant to fluconazole. Micafungin has shown good clinical cure rates (73.5%) in patients with C. glabrata infections 2, and exhibits excellent in vitro activity against C. glabrata isolates, even those resistant to fluconazole 3.
Alternative Treatment Options
When echinocandins cannot be used, consider:
Lipid formulation of amphotericin B: 3-5 mg/kg daily 1
- Less attractive due to potential toxicity concerns
- Historically was a standard treatment before echinocandins 4
For fluconazole-resistant C. glabrata urinary tract infections:
- 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
- Pyelonephritis: Amphotericin B deoxycholate (0.3-0.6 mg/kg daily for 1-7 days) with or without oral flucytosine 1
- Bladder irrigation: Amphotericin B deoxycholate (50 mg/L sterile water daily for 5 days) may be considered for cystitis 1
Treatment Duration and Monitoring
- Continue treatment for at least 2 weeks after documented clearance of Candida from the bloodstream and resolution of symptoms 1
- Perform follow-up blood cultures every day or every other day to establish clearance of candidemia 1
- Remove intravenous catheters in non-neutropenic patients with candidemia 1
- Monitor for adverse effects:
- Echinocandins: Elevated liver enzymes and histamine-mediated reactions
- Amphotericin B: Nephrotoxicity and infusion-related reactions 1
Susceptibility Testing and Resistance Management
- Test for azole susceptibility for all bloodstream and clinically relevant C. glabrata isolates 1
- Consider echinocandin susceptibility testing in patients with prior echinocandin treatment 1
- Higher dosages of echinocandins may be required to achieve fungicidal effects in neutropenic hosts 5
Step-Down Therapy Considerations
Only consider transitioning from an echinocandin to an azole after:
- Clinical improvement
- Confirmation of isolate susceptibility to the azole
- Negative follow-up cultures 1
If transitioning to fluconazole, use higher doses (800 mg daily) and ensure a dose:MIC ratio >12.5 for better outcomes 6.
Important Clinical Considerations
- Severity of illness significantly impacts treatment outcomes - patients in ICU have worse outcomes regardless of antifungal choice 6
- Catheter removal is crucial for improving outcomes in candidemia 6
- C. glabrata has intrinsically reduced susceptibility to azoles, making echinocandins the preferred choice 1
- Voriconazole has limited data specifically for C. glabrata infections, with only 33% success rates reported in some studies 7
Remember that C. glabrata infections can be challenging to treat due to their reduced susceptibility to azoles and potential for developing resistance, making the choice of appropriate initial therapy critical for successful outcomes.