What is the recommended treatment for a patient colonized with Candida glabrata, considering potential antifungal resistance?

Testing and Treatment for Colonized Candida glabrata

Do Not Treat Colonization Alone

Antifungal treatment is NOT recommended for patients colonized with Candida glabrata unless they belong to high-risk groups for dissemination: neutropenic patients, very low-birth-weight infants (<1500 g), or patients undergoing urologic manipulation. 1

• Non-neutropenic critically ill patients with Candida colonization (including respiratory secretions) should not receive antifungal treatment based on colonization alone 1
• The presence of C. glabrata in cultures may reflect colonization rather than true infection, requiring careful clinical assessment before initiating therapy 1

High-Risk Populations Requiring Treatment

Neutropenic Patients

• Treat colonized neutropenic patients as candidemia, even without positive blood cultures 1
• Echinocandins (caspofungin 70 mg loading, then 50 mg daily; micafungin 100 mg daily; or anidulafungin 200 mg loading, then 100 mg daily) are the preferred first-line therapy 2
• Continue therapy for 2 weeks after resolution of neutropenia and symptom resolution 1

Very Low-Birth-Weight Infants

• Treat as candidemia with amphotericin B deoxycholate 1.0 mg/kg/day, fluconazole 12 mg/kg/day, or echinocandin 1
• Continue for 3 weeks if no persistent fungemia or metastatic complications 1

Patients Undergoing Urologic Procedures

• Administer oral fluconazole 400 mg (6 mg/kg) daily OR amphotericin B deoxycholate 0.3-0.6 mg/kg daily for several days before and after the procedure 1

Treatment of Proven C. glabrata Infection

First-Line Therapy

Echinocandins are strongly preferred over fluconazole for C. glabrata infections due to reduced azole susceptibility and increasing resistance rates 2, 1

• Caspofungin: 70 mg loading dose, then 50 mg daily 2
• Micafungin: 100 mg daily 2
• Anidulafungin: 200 mg loading dose, then 100 mg daily 2

Alternative Therapy

• Lipid formulation amphotericin B (3-5 mg/kg daily) if echinocandin intolerance, limited availability, or documented echinocandin resistance 2
• Amphotericin B deoxycholate 0.7-1.0 mg/kg/day is acceptable but less preferred 1

Azole Therapy: Use With Extreme Caution

Fluconazole or voriconazole should NOT be used without confirmed susceptibility testing 2

• Transition to fluconazole (800 mg daily) or voriconazole (200-300 mg twice daily) only if isolates are documented as susceptible 2
• Despite in vitro reduced susceptibility, clinical outcomes with fluconazole may not be inferior to echinocandins when dosed appropriately 1, 3
• A fluconazole dose:MIC ratio >12.5 is associated with significantly higher response rates (49% vs 20%) 3

Step-Down Therapy

Fluconazole step-down after initial echinocandin therapy is safe and reasonable for C. glabrata candidemia when susceptibility is confirmed 4

• Transition timing varies: 5-7 days per IDSA versus 10 days per ESCMID guidelines 1
• Ensure clinical stability, negative follow-up cultures, and documented fluconazole susceptibility before transition 4
• No significant difference in 30-day clinical failure between echinocandin-only (15%) versus fluconazole step-down (9%) 4

Special Considerations for Immunocompromised Patients

MPO-Deficient Patients

• Consider combination therapy with liposomal amphotericin B (3-5 mg/kg daily) plus echinocandin given impaired fungicidal capacity 2
• Continue combination therapy until blood cultures negative for at least 2 weeks and clinical improvement achieved 2

Septic Shock

• Echinocandins are mandatory in hemodynamically unstable patients with suspected C. glabrata 5, 6
• Triazoles are acceptable only in hemodynamically stable patients without prior triazole exposure 5

Essential Monitoring and Source Control

Monitoring Requirements

• Obtain daily or every-other-day blood cultures until clearance documented 2
• Perform dilated ophthalmological examination within the first week after diagnosis 2
• Continue therapy for 2 weeks after documented bloodstream clearance and symptom resolution 2

Source Control

• Remove all intravascular catheters as early as possible when catheter-related infection is suspected 1, 2
• Eliminate urinary tract obstruction and consider removal/replacement of nephrostomy tubes or stents 1

Common Pitfalls to Avoid

• Do not treat colonization in non-high-risk patients - this promotes resistance without clinical benefit 1
• Do not use fluconazole empirically for C. glabrata without susceptibility data - resistance rates are increasing 2, 6
• Do not continue empirical therapy beyond 48-72 hours without reassessment - de-escalate or discontinue if cultures negative and clinical improvement occurs 5
• Do not assume cross-susceptibility between azoles - C. glabrata demonstrates cross-resistance to multiple triazoles 6