Treatment of Candida glabrata and Candida krusei Infections
First-Line Therapy for Invasive Disease/Candidemia
An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line treatment for both C. glabrata and C. krusei invasive infections and candidemia. 1
Echinocandin Dosing
- Caspofungin: 70 mg loading dose, then 50 mg daily 2, 1
- Micafungin: 100 mg daily 1, 3
- Anidulafungin: 200 mg loading dose, then 100 mg daily 1
Both C. glabrata and C. krusei demonstrate susceptibility to echinocandins, making this class superior to azoles for these species 2. Clinical data from pooled trials show micafungin achieves 73.5% clinical cure rates in C. glabrata/krusei infections, with comparable outcomes across echinocandin agents 3.
Alternative Therapy When Echinocandins Cannot Be Used
Amphotericin B deoxycholate is the preferred alternative, though important species-specific differences exist:
For C. glabrata: 0.7 mg/kg/day 2
Step-Down Oral Therapy
Voriconazole (400 mg twice daily for 2 doses, then 200 mg twice daily) can be used as step-down therapy for selected C. krusei cases once the patient is clinically stable 1. Voriconazole is licensed in Europe for fluconazole-resistant serious invasive Candida infections including C. krusei 2.
Critical Adjunctive Measures
Remove central venous catheters as early as possible - this is essential for all patients with candidemia 1, 6. Failure to remove catheters is independently associated with 28-day mortality 3.
Additional required measures include:
- Perform follow-up blood cultures daily or every other day until clearance 1
- Continue treatment for 2 weeks after documented bloodstream clearance and symptom resolution 1
- Perform dilated ophthalmological examination within the first week in all nonneutropenic patients 1
Urinary Tract Infections
When to Treat
Determine whether candiduria represents true infection versus asymptomatic colonization 7, 1. Treatment is warranted for:
- Symptomatic patients 7
- High-risk groups: neutropenic patients, very low birth-weight infants, patients undergoing urologic manipulation 7
Treatment Regimen for C. krusei UTI
Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days is first-line therapy 7, 1. This achieves adequate urinary concentrations and maintains activity against most C. krusei isolates 1.
Alternative: Amphotericin B bladder irrigation (50 mg/L sterile water daily for 5 days) for cystitis only 7
Duration: 2 weeks for both cystitis and pyelonephritis 7, 1
Essential management steps:
- Remove indwelling bladder catheter if present 7, 1
- Eliminate any urinary tract obstruction 7, 1
- Obtain repeat urine cultures to document clearance 7, 1
Special Populations
Neonates
Amphotericin B deoxycholate is preferred due to low toxicity in this population and lack of pharmacokinetic data for echinocandins in neonates 2, 1.
Hematologic Patients
The treatment algorithm remains the same with echinocandins as first-line therapy, but rapidly remove the catheter regardless of species 1.
Common Pitfalls to Avoid
Never use fluconazole for C. krusei - this species has intrinsic resistance mediated by reduced target enzyme sensitivity 4, 5. The FDA label explicitly states C. krusei should be considered resistant to fluconazole 4.
Exercise caution with fluconazole for C. glabrata - while some success has been reported with high-dose fluconazole (12 mg/kg/day or 800 mg/day), efficacy is only 50% and many isolates are intermediately susceptible or resistant due to upregulation of efflux pumps 2, 4, 5. Resistance in C. glabrata typically involves upregulation of CDR genes resulting in multi-azole resistance 4.
Patient characteristics matter more than drug choice - higher severity of illness, neutropenia, medical admission, and failure to remove catheters are independently associated with worse outcomes, regardless of antifungal selected 3.