Treatment of Candida glabrata UTI
For fluconazole-resistant C. glabrata urinary tract infections, use amphotericin B deoxycholate 0.3–0.6 mg/kg IV daily for 1–7 days, or oral flucytosine 25 mg/kg four times daily for 7–10 days, and always remove indwelling urinary catheters when feasible. 1
Initial Assessment and Susceptibility Testing
The critical first step is determining fluconazole susceptibility, as C. glabrata exhibits variable resistance patterns that fundamentally alter treatment selection 1. Unlike C. albicans, C. glabrata is frequently fluconazole-resistant, making empiric fluconazole therapy potentially ineffective 1.
Treatment Algorithm Based on Infection Site
For Cystitis (Lower UTI)
First-line options for fluconazole-resistant C. glabrata:
- Amphotericin B deoxycholate 0.3–0.6 mg/kg IV daily for 1–7 days 1
- Oral flucytosine 25 mg/kg four times daily for 7–10 days 1
- Remove indwelling bladder catheter immediately if present (strong recommendation) 1
Alternative approach for refractory cystitis:
- Amphotericin B bladder irrigation (50 mg/L sterile water daily for 5 days) may be considered, though recurrence rates are high (weak recommendation) 1
- This approach requires an indwelling catheter and is generally discouraged unless systemic therapy fails 1
For Pyelonephritis (Upper UTI)
Treatment options:
- Amphotericin B deoxycholate 0.3–0.6 mg/kg IV daily for 1–7 days, with or without oral flucytosine 25 mg/kg four times daily 1
- Oral flucytosine monotherapy 25 mg/kg four times daily for 2 weeks can be considered (weak recommendation) 1
- Duration: 2 weeks minimum 1
- Eliminate urinary tract obstruction (strong recommendation) 1
- Remove or replace nephrostomy tubes/stents if feasible 1
Critical Management Principles
Catheter Management
Removal of indwelling urinary catheters is essential and strongly recommended, as catheters perpetuate infection and colonization 1. Nearly 50% of asymptomatic candiduria resolves with catheter removal alone 2.
Drug Selection Rationale
Why amphotericin B deoxycholate works:
- Achieves urinary concentrations exceeding MICs for most Candida isolates, including C. glabrata 1
- Effective even at low doses for UTI 1
- Drawbacks: requires IV administration and has nephrotoxicity concerns 1
Why flucytosine works:
- Excreted as active drug in urine with good activity against C. glabrata 1
- Limitations: toxicity and resistance development when used as monotherapy 1
Critical pitfall - Lipid formulations of amphotericin B:
- Do NOT use lipid formulations (liposomal amphotericin B, amphotericin B lipid complex) as they fail to achieve adequate urine concentrations 1
Drugs That Do NOT Work for C. glabrata UTI
Echinocandins (caspofungin, micafungin, anidulafungin):
- Achieve minimal urinary excretion and are generally ineffective for ascending UTIs 1
- Mixed success/failure reports exist, primarily in desperate situations 1, 3
- Exception: May work for hematogenous renal infection (not ascending UTI) due to adequate tissue concentrations 1
- Despite case reports of success 4, 3, guidelines do not recommend echinocandins for routine UTI treatment 1, 2, 5
Other azoles (voriconazole, posaconazole, isavuconazole):
Special Circumstances
Obstructive Uropathy or Fungus Balls
- Surgical or endoscopic intervention is mandatory (strong recommendation) 1
- Antifungal therapy alone will fail without drainage 1, 6
- Irrigation through nephrostomy tubes with amphotericin B deoxycholate 25–50 mg in 200–500 mL sterile water (strong recommendation) 1
- Case reports demonstrate caspofungin failure in obstructive pyonephrosis, requiring drainage plus local amphotericin B 6
High-Risk Patients Requiring Treatment
Even asymptomatic candiduria requires treatment in:
- Neutropenic patients (treat as candidemia) 1
- Very low-birth-weight infants (<1500 g) 1
- Patients undergoing urologic procedures (fluconazole 400 mg daily or amphotericin B 0.3–0.6 mg/kg daily perioperatively) 1
Monitoring and Follow-Up
Treatment adequacy should be assessed by: