Treatment of Candida glabrata Infection
Echinocandins are the first-line treatment for invasive Candida glabrata infections, including candidemia, with specific recommendations varying by infection site and fluconazole susceptibility. 1
Invasive Candidiasis and Candidemia
Initial Therapy
- Start an echinocandin immediately for all suspected or confirmed invasive C. glabrata infections, as this organism has reduced susceptibility to fluconazole and echinocandins provide superior outcomes 1, 2
- Choose one of the following echinocandin regimens 1, 3:
Transition to Fluconazole (Step-Down Therapy)
- Transition to oral fluconazole is appropriate only after meeting ALL of the following criteria 1, 6:
- Patient is clinically stable
- Repeat blood cultures are negative
- Susceptibility testing confirms fluconazole susceptibility (MIC ≤32 μg/mL for dose-dependent susceptible strains)
- Typically occurs within 5–7 days of echinocandin initiation
- Fluconazole dosing for susceptible C. glabrata: 800 mg (12 mg/kg) loading dose, then 400–800 mg (6–12 mg/kg) daily 1, 7
- Recent data confirm that fluconazole step-down is safe and effective for C. glabrata candidemia when susceptibility is confirmed, with no difference in 30-day clinical failure rates compared to continued echinocandin therapy 6
Alternative Agents for Resistant or Intolerant Cases
- Liposomal amphotericin B 3–5 mg/kg IV daily is recommended when echinocandins cannot be used due to resistance, intolerance, or limited availability 3
- Voriconazole 400 mg (6 mg/kg) IV twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily—only if susceptibility testing confirms voriconazole susceptibility 3
Duration of Therapy
- Continue treatment for at least 14 days after documented clearance of candidemia (negative blood cultures) and resolution of clinical signs and symptoms 1, 3
- For deep-seated infections (endocarditis, osteomyelitis, surgical site infections), longer durations are necessary based on clinical response 3
Urinary Tract Infections
Fluconazole-Susceptible C. glabrata
- Cystitis: Oral fluconazole 200 mg (3 mg/kg) daily for 2 weeks 1, 8
- Pyelonephritis: Oral fluconazole 200–400 mg (3–6 mg/kg) daily for 2 weeks 1, 8
- Remove indwelling bladder catheters immediately—this is mandatory and significantly improves cure rates 1, 9
Fluconazole-Resistant C. glabrata
- 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
- Flucytosine monotherapy 25 mg/kg orally four times daily for 2 weeks is a weak alternative for cystitis only 1
- Amphotericin B bladder irrigation (50 mg/L sterile water daily for 5 days) may be used for cystitis when systemic therapy is contraindicated, but has high recurrence rates 1, 9
- Echinocandins are NOT recommended for urinary tract infections because they achieve inadequate urinary concentrations 9
Critical Adjunctive Measures for UTI
- Eliminate urinary tract obstruction (hydronephrosis, stones) through surgical consultation 1, 9
- Remove or replace nephrostomy tubes and ureteral stents when feasible 1, 9
- For fungus balls or renal abscesses, surgical debridement is mandatory in addition to antifungal therapy 1, 9
Surgical Site and Wound Infections
- Echinocandins remain first-line as outlined above for invasive infections 3
- Surgical debridement and source control are essential—remove all foreign material, necrotic tissue, and infected devices 3
- Adequate drainage and wound care are mandatory for successful treatment 3
- Continue therapy for at least 14 days after documented clearance and resolution of signs/symptoms 3
Antifungal Susceptibility Testing
- Obtain susceptibility testing for all bloodstream and clinically relevant C. glabrata isolates 1, 3
- Test for azole susceptibility in all cases 1
- Test for echinocandin susceptibility in patients with prior echinocandin exposure or treatment failure 1, 3
- C. glabrata exhibits intrinsically reduced susceptibility to azoles and can rapidly develop echinocandin resistance 2, 10
Special Populations
High-Risk Patients Requiring Treatment
- Neutropenic patients and very low birth weight infants (<1500 g) with C. glabrata candiduria should be treated as having candidemia, not simple UTI 1, 9
- Patients undergoing urologic procedures should receive prophylactic 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
Hemodialysis Patients
- For fluconazole-susceptible organisms, administer fluconazole 200 mg after each hemodialysis session 8
Critical Pitfalls to Avoid
- Do NOT use fluconazole as initial empiric therapy for suspected C. glabrata invasive infections—this organism has reduced susceptibility and fluconazole use is associated with treatment failure 1, 2, 11
- Do NOT use echinocandins for urinary tract infections—they do not achieve therapeutic urinary concentrations 9
- Do NOT use lipid formulations of amphotericin B for UTIs—they also fail to achieve adequate urine levels 9
- Do NOT use flucytosine monotherapy for invasive infections—resistance develops rapidly 3, 9
- Do NOT continue therapy without removing indwelling catheters—failure to remove catheters is strongly associated with treatment failure and recurrence 1, 3, 9
- Do NOT treat asymptomatic candiduria unless the patient is neutropenic, very low birth weight, or undergoing urologic procedures 1, 9
Monitoring During Therapy
- Assess clinical response within 48–72 hours and modify therapy if improvement is not observed 3
- Obtain repeat blood cultures to document clearance 1, 6
- For amphotericin B: monitor renal function (creatinine, BUN) and electrolytes (potassium, magnesium) at least twice weekly; pre-hydrate with normal saline to mitigate nephrotoxicity 9
- For amphotericin B: monitor complete blood count weekly due to risk of anemia 9