What treats Candida glabrata infections?

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 Options

Echinocandins (Recommended First-Line)

• Caspofungin: Loading dose 70 mg, then 50 mg daily 2, 1
• Micafungin: 100 mg daily 2, 1, 3
• Anidulafungin: Loading dose 200 mg, then 100 mg daily 2, 1

Echinocandins work by inhibiting the synthesis of 1,3-beta-D-glucan, an essential component of fungal cell walls that is not present in mammalian cells 3. This mechanism makes them highly effective against C. glabrata, which has increasing rates of resistance to azole antifungals.

Alternative Treatment Options

For Patients Who Cannot Receive Echinocandins

• Lipid formulation of amphotericin B: 3-5 mg/kg daily 1
  • Less preferred due to potential toxicity concerns, particularly nephrotoxicity

For Fluconazole-Susceptible Isolates

• Fluconazole: Higher dose of 800 mg (12 mg/kg) daily can be considered for step-down therapy, but only after:

  1. Confirming isolate susceptibility to fluconazole
  2. Patient is clinically stable
  3. Negative repeat blood cultures 2, 1

• Voriconazole: 200-300 mg (3-4 mg/kg) twice daily can be considered as step-down therapy only for susceptible isolates 2, 1

Treatment for Specific C. glabrata Infections

For Fluconazole-Resistant C. glabrata Cystitis

• Amphotericin B deoxycholate: 0.3-0.6 mg/kg daily for 1-7 days 1
• Oral flucytosine: 25 mg/kg 4 times daily for 7-10 days 1
• Amphotericin B deoxycholate bladder irrigation: 50 mg/L sterile water daily for 5 days 1

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 1

Treatment Duration and Monitoring

• Continue treatment for at least 2 weeks after:

  1. Documented clearance of Candida from the bloodstream
  2. Resolution of symptoms attributable to candidemia 1

• Follow-up blood cultures should be performed daily or every other day to establish clearance of candidemia 1

• For candidemia, intravenous catheter removal is strongly recommended for non-neutropenic patients 1

• Monitor for potential adverse effects:

  • With echinocandins: elevated liver enzymes and histamine-mediated reactions 1, 3
  • With amphotericin B: nephrotoxicity and infusion-related reactions 1

Susceptibility Testing

• 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

Important Clinical Considerations

• Recent research suggests that while fluconazole step-down therapy appears to be safe in select patients with C. glabrata candidemia, initial echinocandin therapy remains crucial 4

• Dose escalation of echinocandins beyond standard dosing does not appear to improve efficacy against C. glabrata 5

• Patient factors such as severity of illness and catheter management appear to be more important determinants of clinical outcomes than the specific echinocandin chosen 6

• For fluconazole treatment, a dose:MIC ratio >12.5 is associated with significantly higher response rates, supporting the need for susceptibility testing 7

• The prolonged post-antifungal effect of echinocandins, especially anidulafungin and caspofungin, contributes to their efficacy against C. glabrata 8