How should I treat a patient with candidemia of unknown species, including initial antifungal choice, catheter removal, step‑down therapy, treatment duration, and monitoring?

Management of Candidemia of Unknown Species

Start an echinocandin immediately as first-line therapy for candidemia of unknown species, particularly if the patient is moderately to severely ill or has recent azole exposure. 1

Initial Antifungal Selection

Echinocandin therapy is the preferred initial approach based on superior outcomes in critically ill patients and broad activity against all Candida species, including azole-resistant organisms. 1

Dosing Options (all three are interchangeable):

• Caspofungin: 70 mg loading dose, then 50 mg daily 1
• Micafungin: 100 mg daily 1
• Anidulafungin: 200 mg loading dose, then 100 mg daily 1

Alternative Initial Therapy:

Fluconazole (800 mg loading dose, then 400 mg daily) is acceptable ONLY if the patient meets ALL of the following criteria: 1

• Hemodynamically stable (not critically ill)
• No azole exposure in the past 90 days
• Not elderly, diabetic, or immunocompromised (low risk for C. glabrata)
• No suspected endocarditis or CNS involvement

Liposomal amphotericin B (3-5 mg/kg daily) is reserved for intolerance or unavailability of echinocandins and fluconazole. 1

Critical Source Control

Remove all central venous catheters within 24-48 hours in non-neutropenic patients—this is non-negotiable and independently associated with lower mortality. 1 Catheter retention significantly increases mortality risk and treatment failure. 1

In neutropenic patients, catheter removal should be strongly considered but may be deferred if clinically necessary. 1

Monitoring and Diagnostic Workup

Immediate Actions:

• Obtain blood cultures daily until clearance is documented (at least one negative culture). 1
• Send isolate for species identification and susceptibility testing immediately. 1
• Perform dilated fundoscopic examination within the first week to rule out endophthalmitis. 1, 2
• Consider transesophageal echocardiography if endocarditis is suspected (persistent candidemia, new murmur, embolic phenomena). 1

Step-Down Therapy

Transition to fluconazole (400 mg daily) is appropriate when ALL of the following are met: 1

• Patient is clinically stable and improving
• Blood cultures have cleared (documented negative)
• Species identified as fluconazole-susceptible (C. albicans, C. parapsilosis, C. tropicalis)
• Typically occurs after 5-7 days of echinocandin therapy 1, 3

Species-Specific Considerations After Identification:

C. albicans: Step down to fluconazole once stable and cultures clear. 1

C. glabrata: Continue echinocandin throughout treatment course; do NOT switch to fluconazole without documented susceptibility. 1 If patient was started on fluconazole and is improving with negative follow-up cultures, continuing fluconazole is reasonable. 1

C. parapsilosis: Fluconazole is preferred if susceptible, but if patient is improving on echinocandin with negative cultures, continuing the echinocandin is acceptable. 1

C. krusei: Continue echinocandin or switch to voriconazole (400 mg twice daily for 2 doses, then 200 mg twice daily); fluconazole is intrinsically resistant. 1

Treatment Duration

Continue antifungal therapy for a minimum of 14 days AFTER: 1

• Documented clearance of Candida from bloodstream (negative blood cultures)
• AND resolution of all symptoms attributable to candidemia
• AND resolution of neutropenia (if applicable)

Common pitfall: Do not count treatment duration from the start of therapy—the 14-day clock begins only after blood cultures clear and symptoms resolve. 1

Key Clinical Pearls

Early therapy initiation is critical—delayed or inadequate antifungal therapy significantly increases mortality. 1 Start empiric echinocandin therapy immediately when candidemia is suspected in high-risk patients, even before culture confirmation. 1

Risk factors predicting worse outcomes include: 1

• Higher APACHE II scores
• Advanced age
• C. tropicalis infection
• Catheter retention
• Delayed antifungal initiation

Echinocandin resistance is rare (<2% in most Candida species) but increasing in C. glabrata (up to 7% in some centers). 2 Always obtain susceptibility testing. 1

Do not use amphotericin B deoxycholate as first-line therapy due to severe toxicity; lipid formulations are preferred if amphotericin is needed. 1