What is the best treatment for systemic candidiasis (thrush)?

Treatment of Systemic Candidiasis (Invasive Candidiasis/Candidemia)

For systemic candidiasis, an echinocandin (caspofungin, micafungin, or anidulafungin) is the first-line treatment for most patients, particularly those who are critically ill, have had recent azole exposure, or are at risk for fluconazole-resistant species. 1

Initial Treatment Selection

First-Line Therapy: Echinocandins

The preferred initial regimen for invasive candidiasis is an echinocandin 1:

• 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

Echinocandins are strongly recommended as initial therapy because they demonstrate high efficacy with superior safety profiles compared to amphotericin B formulations, particularly avoiding nephrotoxicity 2. They are the preferred choice for critically ill patients 1, 3.

Alternative First-Line: Fluconazole (Selected Patients Only)

Fluconazole (800 mg loading dose, then 400 mg daily) is an acceptable alternative ONLY in patients who are:

• Not critically ill 1
• Have no recent azole exposure 1
• Are unlikely to have fluconazole-resistant Candida species 1

Recent evidence suggests that among immunocompromised or ICU patients, severity of illness rather than initial antifungal choice drives outcomes, though echinocandins remain preferred for high-risk populations 4.

Species-Specific Considerations

C. glabrata Infections

• Echinocandin is strongly preferred 1
• Liposomal amphotericin B (3-5 mg/kg daily) is an effective but less attractive alternative 1

C. parapsilosis Infections

• Fluconazole or liposomal amphotericin B preferred as initial therapy 1
• If already receiving an echinocandin with clinical stability and negative follow-up cultures, continuing the echinocandin is reasonable 1

C. krusei Infections

• Echinocandin, liposomal amphotericin B, or voriconazole recommended 1

Essential Concurrent Interventions

Central Venous Catheter Management

Removal of all central venous catheters is strongly recommended for all patients with candidemia 1, 5. This is a critical component of therapy that significantly impacts outcomes.

Susceptibility Testing

Testing for azole susceptibility is mandatory for all bloodstream and clinically relevant Candida isolates 1. Echinocandin susceptibility testing should be considered in patients with prior echinocandin exposure or infections with C. glabrata or C. parapsilosis 1.

Duration of Therapy

Treatment should continue for 2 weeks after:

• Documented clearance of Candida from the bloodstream 1
• Resolution of symptoms attributable to candidemia 1
• Resolution of neutropenia (if applicable) 1

This applies to candidemia without persistent fungemia or metastatic complications 1.

Alternative Agents

Lipid Formulation Amphotericin B

Liposomal amphotericin B (3-5 mg/kg daily) is recommended for patients with intolerance to echinocandins or limited availability of other antifungals 1. While effective, it carries higher toxicity risk than echinocandins, particularly nephrotoxicity 2.

Voriconazole

Voriconazole can be used when additional mold coverage is desired 1. For invasive aspergillosis or other mold infections, voriconazole dosing is 6 mg/kg IV every 12 hours for the first 24 hours, then 4 mg/kg every 12 hours 6.

Common Pitfalls to Avoid

• Do not rely on fluconazole as first-line in critically ill patients - echinocandins have superior outcomes in this population 1
• Do not leave central venous catheters in place - catheter retention significantly worsens outcomes 1, 5
• Do not use azoles empirically in patients who received azole prophylaxis - resistance is likely 1
• Do not stop therapy prematurely - ensure full 2-week course after blood culture clearance 1
• Do not assume all Candida species have the same susceptibility - species identification and susceptibility testing are essential 1

Step-Down Therapy

After clinical improvement and documented negative blood cultures, transition from IV to oral therapy may be appropriate for fluconazole-susceptible isolates in stable patients 1. Continue the same agent if possible, ensuring adequate oral bioavailability and patient tolerance.