What is the recommended treatment for a patient diagnosed with Candida glabrata infection?

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 2, 1
• Micafungin: 100 mg daily 2, 1
• Anidulafungin: Loading dose of 200 mg, then 100 mg daily 2, 1

Echinocandins are recommended as first-line therapy for C. glabrata infections because:

• C. glabrata has intrinsic reduced susceptibility to fluconazole
• Clinical studies show better outcomes with echinocandins compared to azoles
• Micafungin has demonstrated efficacy against C. glabrata with clinical cure rates of 69.6% 3

Alternative Treatment Options

Lipid Formulation of Amphotericin B (Second-Line)

• 3-5 mg/kg daily 2, 1
• Consider when echinocandins are unavailable or contraindicated
• Less attractive option due to potential nephrotoxicity and infusion-related reactions

Fluconazole/Voriconazole Considerations

• Do not transition to fluconazole or voriconazole without confirmation of isolate susceptibility 2, 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 2
• Voriconazole may be used as step-down oral therapy for selected cases of voriconazole-susceptible C. glabrata 2

Special Situations

Urinary Tract Infections

• For 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 2
• For fluconazole-resistant C. glabrata pyelonephritis:
  • Amphotericin B deoxycholate, 0.3-0.6 mg/kg daily for 1-7 days with or without oral flucytosine 2
• Consider amphotericin B deoxycholate bladder irrigation (50 mg/L sterile water daily for 5 days) for cystitis due to fluconazole-resistant C. glabrata 2

Treatment Duration and Monitoring

• Continue treatment for at least 2 weeks after documented clearance of Candida from the bloodstream and resolution of symptoms attributable to candidemia 2, 1
• Intravenous catheter removal is strongly recommended for non-neutropenic patients with candidemia 2, 1
• 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

Clinical Pearls and Pitfalls

Pearls

• Patient characteristics and catheter management significantly affect clinical outcomes, sometimes more than the choice of antifungal agent 4
• Micafungin has demonstrated similar outcomes to comparators for C. glabrata infections, with the standard 100 mg/day dose being an acceptable option 4

Pitfalls to Avoid

• Failing to remove central venous catheters when possible, as this is associated with increased mortality 4
• Automatically using fluconazole without susceptibility testing for C. glabrata
• Neglecting to consider combination therapy in severe or refractory cases - micafungin plus amphotericin B has shown synergistic effects in reducing fungal load in experimental models 5
• Underestimating the importance of controlling underlying conditions like poorly controlled diabetes that can enhance the development of C. glabrata infections 6

By following these evidence-based recommendations, clinicians can optimize outcomes in patients with C. glabrata infections, reducing morbidity and mortality associated with these challenging infections.