What is the recommended treatment for an adult patient with PCR‑positive Candida glabrata and Candida krusei infection?

Treatment of PCR-Positive Candida glabrata and Candida krusei Co-Infection

Immediate First-Line Therapy

Initiate an echinocandin immediately as first-line therapy for this dual infection, given that C. krusei is intrinsically resistant to fluconazole and C. glabrata has reduced azole susceptibility. 1, 2, 3

Echinocandin Dosing Options (Choose One)

• Caspofungin: 70 mg IV loading dose, then 50 mg IV daily 3
• Micafungin: 100 mg IV daily 3, 4
• Anidulafungin: 200 mg IV loading dose, then 100 mg IV daily 3

All three echinocandins are considered interchangeable and demonstrate fungicidal activity against both C. glabrata and C. krusei with approximately 75% success rates in clinical trials 1. Micafungin specifically has demonstrated comparable outcomes to other agents for both C. glabrata and C. krusei infections 4.

Critical Initial Management Steps

Source Control (Mandatory)

• Remove all central venous catheters immediately in non-neutropenic patients 3
• Remove or replace any indwelling urinary catheters if urinary tract involvement is present 2
• Eliminate any urinary tract obstruction through surgical consultation if needed 2
• Failure to remove catheters is directly linked to treatment failure and recurrence 2

Diagnostic Workup

• Obtain blood cultures daily or every other day until clearance is documented 3
• Perform dilated ophthalmologic examination within the first week to rule out endophthalmitis 3
• Order azole susceptibility testing for the C. glabrata isolate (mandatory for all blood and sterile site isolates) 3
• Consider echinocandin susceptibility testing if the patient has prior echinocandin exposure 3

Why Fluconazole Cannot Be Used

Do not use fluconazole for this co-infection under any circumstances because:

• C. krusei exhibits intrinsic resistance to fluconazole, making it completely ineffective 2, 5
• C. glabrata has intrinsic reduced susceptibility to azoles, with 9.7% of isolates being fluconazole-resistant 6
• Among fluconazole-resistant C. glabrata, 11.1% also demonstrate echinocandin resistance, representing emerging co-resistance 6

Step-Down Therapy Considerations

For C. glabrata (If Susceptibility Confirmed)

After 5-7 days of echinocandin therapy, transition to oral fluconazole is possible only if:

• The patient is clinically stable with negative repeat blood cultures 3, 7
• Susceptibility testing confirms fluconazole susceptibility (MIC <32 μg/mL) 3
• Fluconazole 800 mg (12 mg/kg) daily is the appropriate step-down dose 3

Recent data from 2025 demonstrates that fluconazole step-down therapy for C. glabrata candidemia shows no significant difference in 30-day clinical failure (9% vs 15%, P=0.58) or persistent candidemia (24% vs 22%, P=0.7) compared to continued echinocandin therapy 7.

For C. krusei Component

C. krusei requires continued echinocandin therapy or alternative non-fluconazole agents because fluconazole step-down is contraindicated 2. If oral therapy is absolutely necessary and the isolate is voriconazole-susceptible, voriconazole 200-300 mg twice daily may be considered, though this is less ideal 1, 3.

Alternative Agents (If Echinocandin Intolerance/Resistance)

Amphotericin B Options

• Amphotericin B deoxycholate: 0.5-1.0 mg/kg IV daily (for systemic infection) or 0.3-0.6 mg/kg IV daily for 1-7 days (for urinary tract infection) 2, 3
• Lipid formulation amphotericin B: 3-5 mg/kg IV daily 3
• Critical caveat: Lipid formulations do NOT achieve adequate urinary concentrations and should be avoided if urinary tract infection is present 2

Amphotericin B Monitoring Requirements

• No dose reduction needed for renal impairment, but the drug itself is nephrotoxic 2
• Pre-hydrate with normal saline to mitigate nephrotoxicity 2
• Monitor renal panel (creatinine, BUN, potassium, magnesium) at least twice weekly 2
• Monitor complete blood count weekly due to risk of anemia 2

Treatment Duration

Continue therapy for a minimum of 2 weeks after documented blood culture clearance and complete resolution of symptoms (fever, hemodynamic instability) 1, 3. For deep tissue infections or complicated cases, longer courses are required based on the specific site and clinical response 3.

Site-Specific Considerations

If Urinary Tract Involvement

• Echinocandins achieve minimal urinary concentrations and are NOT recommended for UTIs 2
• Amphotericin B deoxycholate 0.3-0.6 mg/kg IV daily for 1-7 days is the only appropriate systemic option for C. krusei UTI 2
• Bladder irrigation (if systemic therapy contraindicated and infection confined to bladder): amphotericin B 50 mg/L sterile water instilled daily for 5 days, though this has high recurrence rates 2

If Endocardial or CNS Involvement Suspected

Do not use fluconazole or echinocandins; use amphotericin B as it is fungicidal and achieves better CNS penetration 1.

Common Pitfalls to Avoid

• Never use fluconazole as initial or step-down therapy without confirmed C. glabrata susceptibility and recognition that C. krusei will remain untreated 2, 5
• Never use echinocandins for urinary tract infections due to inadequate urinary drug levels 2
• Never continue therapy without removing catheters—this is the most common cause of treatment failure 2, 3
• Never use lipid amphotericin formulations for UTIs 2
• Never assume azole susceptibility—always obtain susceptibility testing for C. glabrata 3
• Never delay therapy—higher mortality is associated with delayed antifungal treatment 1

Monitoring Treatment Response

• Daily blood cultures until two consecutive negative cultures are obtained 3
• Clinical assessment for resolution of fever, hemodynamic stability, and symptom improvement 3
• Repeat ophthalmologic examination if initial exam was positive or if symptoms develop 3
• Renal function and electrolytes if using amphotericin B 2