What is the recommended treatment for Candida glabata infections?

Treatment of Candida glabrata Infections

An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line treatment for Candida glabrata infections due to its intrinsic reduced susceptibility to fluconazole. 1

First-line Treatment Options

Echinocandins (Preferred)

• Caspofungin: Loading dose of 70 mg, then 50 mg daily 1
• Micafungin: 100 mg daily 1
• Anidulafungin: Loading dose of 200 mg, then 100 mg daily 1

The Infectious Diseases Society of America (IDSA) strongly recommends echinocandins as initial therapy for C. glabrata infections based on high-quality evidence 1. This recommendation is particularly important because C. glabrata frequently demonstrates reduced susceptibility to azoles.

Alternative Options

• Lipid formulation of amphotericin B (LFAmB): 3-5 mg/kg daily 1
  • Consider when echinocandins are unavailable or contraindicated
  • Less attractive alternative due to potential toxicity concerns 1

Susceptibility Testing

• Testing for azole susceptibility is strongly recommended for all bloodstream and clinically relevant C. glabrata isolates 1
• Testing for echinocandin susceptibility should be considered in patients who have had prior treatment with an echinocandin 1
• Recent studies have documented emergence of co-resistance to both azoles and echinocandins in clinical isolates of C. glabrata 2

Step-Down Therapy

• Do not transition to fluconazole or voriconazole without confirmation of isolate susceptibility 1
• If the patient initially received fluconazole or voriconazole, is clinically improved, and follow-up cultures are negative, continuing the azole to completion is reasonable 1
• For higher-dose fluconazole step-down (if susceptibility is confirmed): 800 mg (12 mg/kg) daily 1
• Voriconazole can be used as step-down therapy for voriconazole-susceptible C. glabrata: 200 mg (3 mg/kg) twice daily after loading dose 1

Treatment Duration

• Continue treatment for at least 2 weeks after documented clearance of Candida from the bloodstream and resolution of symptoms attributable to candidemia 1, 3
• For candidemia without obvious metastatic complications, this duration is typically sufficient 1

Additional Management

• Intravenous catheter removal is strongly recommended for non-neutropenic patients with candidemia 1, 3
• Ophthalmologic examination should be performed to rule out endophthalmitis 3

Special Considerations

Refractory Cases

• Higher dosages of echinocandins may be required to achieve fungicidal effects in neutropenic hosts with C. glabrata infections 4
• For difficult-to-treat infections, combination therapy with liposomal amphotericin B and an echinocandin has shown improved outcomes in experimental models 5

Emerging Resistance

• Recent surveillance data shows increasing rates of echinocandin resistance among fluconazole-resistant C. glabrata isolates 2
• Approximately 9.3% of fluconazole-resistant C. glabrata isolates showed resistance to echinocandins in recent studies 2
• Resistance is associated with mutations in the fks1 or fks2 genes 2

Monitoring

• Follow blood cultures to document clearance of infection
• Monitor for potential adverse effects:
  • Echinocandins: elevated liver enzymes, histamine-mediated reactions 6, 7
  • Amphotericin B: nephrotoxicity, infusion-related reactions

The treatment of C. glabrata infections requires careful consideration of antifungal susceptibility patterns. Given the increasing reports of resistance, susceptibility testing plays a crucial role in guiding therapy, especially in patients who have had prior exposure to antifungals.