What antifungals are effective against Candida Glabrata?

Antifungal Treatment for Candida Glabrata

Echinocandins (anidulafungin, micafungin, or caspofungin) are the first-line agents for treating C. glabrata infections due to their fungicidal activity and superior efficacy compared to azoles, which face increasing resistance rates. 1

First-Line Therapy: Echinocandins

All three echinocandins are preferred initial therapy for C. glabrata infections, with the following dosing regimens 1:

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

The rationale for prioritizing echinocandins includes 1:

• Fungicidal activity against all Candida species including C. glabrata
• Favorable safety profile with minimal drug interactions
• Success rates of approximately 75% in randomized trials
• Particularly indicated for patients with moderate-to-severe illness, recent azole exposure, or high risk of C. glabrata infection

Second-Line Therapy: Amphotericin B

Lipid formulation amphotericin B (3-5 mg/kg daily) is the preferred alternative when 1, 2:

• Echinocandin intolerance develops
• Documented echinocandin resistance exists
• Multidrug-resistant (azole + echinocandin) C. glabrata is suspected

Amphotericin B deoxycholate (0.7-1.0 mg/kg/day) remains an option but is less preferred due to toxicity 1.

Azole Therapy: Use Only With Documented Susceptibility

Fluconazole and voriconazole should NOT be used without confirmed susceptibility testing 1, 2. This critical caveat exists because:

• C. glabrata has innate reduced susceptibility to azoles 3
• Fluconazole resistance rates are increasing, particularly in North America (10.6%) and Asia-Pacific (6.8%) 1
• Cross-resistance between fluconazole and echinocandins is documented in 11.1% of fluconazole-resistant isolates 4

If susceptibility is confirmed, step-down therapy options include 1:

• Fluconazole: 800 mg daily (only for clinically improved patients with negative follow-up cultures)
• Voriconazole: 400 mg twice daily for 2 doses, then 200 mg twice daily (for voriconazole-susceptible C. glabrata)

Critical Management Principles

Essential adjunctive measures include 1, 2:

• Remove central venous catheters as early as possible
• Obtain follow-up blood cultures daily or every other day until clearance documented
• Perform dilated funduscopic examination within the first week (16% of candidemia patients develop ocular involvement)
• Continue therapy for 2 weeks after documented bloodstream clearance and symptom resolution

Emerging Resistance Concerns

The emergence of multidrug-resistant C. glabrata is well-documented 1, 4:

• Echinocandin resistance has emerged, associated with FKS gene mutations
• 9.3% of fluconazole-resistant isolates now show echinocandin resistance (compared to 0% in 2001-2004)
• Clinical failures with breakthrough infections have been reported

When multidrug resistance is proven or suspected, lipid formulation amphotericin B is currently favored until more data become available 1.

Special Considerations

For urinary tract infections caused by C. glabrata, amphotericin B deoxycholate (0.3-0.6 mg/kg daily for 1-7 days) achieves adequate urinary concentrations, though echinocandins have shown success in case reports 5.

Pharmacokinetic considerations in critically ill patients may require dose adjustments, particularly for echinocandins which are highly protein-bound (>95%) and may have reduced exposure in patients with hypoalbuminemia, increased body weight, or renal replacement therapy 1.