What is the primary treatment for a patient with a confirmed diagnosis of Candida glabrata infection?

Treatment for Candida glabrata Infection

An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line treatment for Candida glabrata infections. 1

Initial Therapy Selection

Preferred First-Line: Echinocandins

The Infectious Diseases Society of America guidelines explicitly recommend echinocandins as preferred therapy for C. glabrata infections due to this species' intrinsic reduced susceptibility to azoles. 1, 2 The three echinocandins are considered interchangeable, with the following dosing regimens:

• Caspofungin: 70 mg loading dose on day 1, then 50 mg daily 1, 2, 3
• Micafungin: 100 mg daily 1, 2, 4
• Anidulafungin: 200 mg loading dose, then 100 mg daily 1, 2

Echinocandins demonstrate fungicidal activity against all Candida species and have a favorable safety profile with minimal drug interactions. 1 They are particularly favored for patients with recent azole exposure, moderately severe to severe illness, or hemodynamic instability. 1, 2

Alternative: Lipid Formulation Amphotericin B

Lipid formulation amphotericin B (LFAmB) at 3-5 mg/kg daily is an effective but less attractive alternative when echinocandins cannot be used due to intolerance or resistance. 1, 2 Amphotericin B deoxycholate (0.5-1.0 mg/kg daily) is even less preferred due to higher toxicity risk. 1, 2

Conditional Use of Fluconazole

Fluconazole should only be considered for C. glabrata if all of the following criteria are met: 1, 2

• Patient is less critically ill and hemodynamically stable
• No recent azole exposure
• Susceptibility testing confirms fluconazole susceptibility (mandatory for all C. glabrata isolates from blood and sterile sites) 2
• Dosing: 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily 1

Critical caveat: A dose:MIC ratio >12.5 is associated with significantly higher response rates when fluconazole is used (49% vs 20% for ratios ≤12.5). 5 However, fluconazole should not be first-line empiric therapy for C. glabrata given the species' reduced azole susceptibility. 1, 2

Step-Down Therapy

Transition from intravenous echinocandin to oral azole therapy is reasonable only when: 1, 2

• Patient is clinically stable with documented clinical improvement
• Repeat blood cultures are negative
• Susceptibility testing confirms azole susceptibility
• Minimum 5-7 days of echinocandin therapy completed 2

Step-down options (species-dependent):

• Fluconazole: 800 mg (12 mg/kg) daily for fluconazole-susceptible isolates 2, 6
• Voriconazole: 200-300 mg (3-4 mg/kg) twice daily for voriconazole-susceptible isolates 1, 2

Recent data suggest fluconazole step-down is safe and reasonable in C. glabrata candidemia when appropriately selected, with no significant difference in 30-day clinical failure compared to continued echinocandin therapy (9% vs 15%). 6

Essential Adjunctive Measures

Catheter Management

• Remove central venous catheters in all non-neutropenic patients with candidemia (strongly recommended) 1, 2
• Consider catheter removal in neutropenic patients 1
• Remove or replace indwelling urinary catheters when feasible for cystitis 2

Monitoring Requirements

• Perform daily or every-other-day follow-up blood cultures until clearance is documented 2
• Conduct dilated ophthalmologic examination within the first week after diagnosis to assess for endophthalmitis 2
• Mandatory susceptibility testing for azoles on all C. glabrata isolates from blood and sterile sites 2
• Consider echinocandin susceptibility testing in patients with prior echinocandin exposure 2

Treatment Duration

Continue therapy for 2 weeks after documented clearance of Candida from the bloodstream AND resolution of symptoms attributable to candidemia. 1, 2 This applies to candidemia without persistent fungemia or metastatic complications. 1

Deep tissue infections require longer treatment courses based on the specific site and clinical response. 2

Site-Specific Considerations

Cystitis

• Fluconazole-susceptible C. glabrata: Oral fluconazole 200 mg daily for 2 weeks 2
• Fluconazole-resistant C. glabrata: Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days OR oral flucytosine 25 mg/kg four times daily for 7-10 days 2

Endocardial or CNS Involvement

Patients with suspected endocardial or CNS involvement should receive fungicidal agents rather than fluconazole as initial therapy—either amphotericin B (for both sites) or an echinocandin (for endocardial candidiasis). 1

Special Populations

Neutropenic Patients

Echinocandins remain preferred, though higher dosages may be required to achieve fungicidal effects in neutropenic hosts based on pharmacodynamic modeling. 7 The standard licensed regimens are predicted to result in fungistatic rather than fungicidal effects in this population. 7

Critically Ill Patients

Echinocandins are strongly preferred over fluconazole for hemodynamically unstable patients or those with moderately severe to severe illness. 1, 2

Common Pitfalls to Avoid

• Do not use fluconazole empirically for suspected C. glabrata without susceptibility data 1, 2
• Do not use azoles for empirical therapy in patients who have received azole prophylaxis 1
• Do not delay catheter removal in non-neutropenic patients—this is strongly associated with improved outcomes 1, 2
• Do not assume all echinocandins are equally effective for C. parapsilosis—fluconazole is preferred for this species due to reduced echinocandin activity 1
• Do not transition to oral therapy prematurely—ensure clinical stability, negative cultures, and documented susceptibility first 1, 2