How should Candida glabrata and Candida dubliniensis infections be treated?

Treatment of Candida glabrata and Candida dubliniensis Infections

For invasive infections including candidemia, start with an echinocandin (caspofungin 70 mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading dose then 100 mg daily) as first-line therapy for both C. glabrata and C. dubliniensis. 1

Initial Treatment Approach

For Invasive Candidiasis/Candidemia

• Echinocandins are the gold standard initial therapy for both species, particularly for C. glabrata which has intrinsic reduced azole susceptibility 1
• Fluconazole 800 mg loading dose, then 400 mg daily is acceptable ONLY if:
  • Patient is not critically ill
  • C. dubliniensis is suspected (generally fluconazole-susceptible) 2
  • Patient is unlikely to have fluconazole-resistant organism 1

Critical Management Steps

Always obtain susceptibility testing for all bloodstream and clinically relevant isolates - this is mandatory for guiding subsequent therapy 1

For C. glabrata specifically:

• Echinocandin susceptibility testing should be performed, especially if prior echinocandin exposure 1
• Do NOT transition to fluconazole unless susceptibility is confirmed 1
• If transitioning to fluconazole after clinical stability (5-7 days), use higher doses: 800 mg (12 mg/kg) daily 1
• Recent evidence supports fluconazole step-down as safe when susceptibility confirmed 3

For C. dubliniensis:

• Generally more susceptible to azoles than C. glabrata 2
• Can develop fluconazole resistance, so susceptibility testing remains essential 2
• Responds well to standard echinocandin therapy 2

Site-Specific Treatment Modifications

Urinary Tract Infections

Cystitis:

• Fluconazole-susceptible organisms: Oral fluconazole 200 mg daily for 2 weeks 1
• Fluconazole-resistant C. glabrata: 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
• Remove indwelling bladder catheter - this is critical and strongly recommended 1

Pyelonephritis:

• Fluconazole-susceptible: Oral fluconazole 200-400 mg daily for 2 weeks 1
• Fluconazole-resistant C. glabrata: Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days with or without flucytosine 25 mg/kg 4 times daily 1

CNS Infections (Meningitis)

• Liposomal amphotericin B 5 mg/kg daily with or without flucytosine 25 mg/kg 4 times daily 1
• Step-down to fluconazole 400-800 mg daily after clinical response 1
• C. glabrata CNS infections carry extremely high mortality even with appropriate therapy 4
• Continue therapy until complete resolution of CSF and radiological abnormalities 1

Refractory or Resistant Infections

When echinocandin AND azole resistance suspected:

• Lipid formulation amphotericin B 3-5 mg/kg daily 1
• Consider combination therapy with echinocandin plus liposomal amphotericin B for multidistrict infections 5

For refractory vaginal C. glabrata:

• Topical flucytosine 1 g plus amphotericin B 100 mg in lubricating jelly base, 8 g total dose intravaginally daily for 14 days 6

Duration and Monitoring

• Candidemia without metastatic complications: Continue for 2 weeks after documented clearance from bloodstream and symptom resolution 1
• Obtain daily or every-other-day blood cultures until clearance documented 1
• Ophthalmologic examination within first week for all nonneutropenic patients with candidemia 1
• Treatment duration for complicated infections: minimum 4-6 weeks depending on lesion resolution 1

Key Pitfalls to Avoid

1. Never use fluconazole empirically for C. glabrata without susceptibility data - resistance rates are significant
2. Do not assume C. dubliniensis is fluconazole-susceptible - resistance develops easily 2
3. Source control is mandatory - remove catheters, drain abscesses, address urinary obstruction 1
4. Do not undertreate CNS infections - these require prolonged therapy and have high mortality 4
5. For persistent candidemia despite echinocandins, consider pharmacokinetic barriers and escalate to combination therapy 5