What are the first-line and second-line antifungal treatments for Candida species infections?

Antifungal Treatment for Candida Species Infections

First-Line Therapy

For critically ill patients or those with recent azole exposure, echinocandins (caspofungin, micafungin, or anidulafungin) are the recommended first-line agents. 1

Echinocandin Dosing:

• 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

When to Choose Echinocandins:

• Moderately severe to severe illness (hemodynamically unstable patients) 1
• Recent azole exposure 1
• High risk of C. glabrata or C. krusei infection (elderly, cancer patients, diabetics) 1
• Suspected or confirmed C. glabrata infection 1
• C. auris candidemia 1

Alternative First-Line Therapy

Fluconazole is recommended as first-line therapy for non-critically ill patients without recent azole exposure and with low risk of resistant species. 1

Fluconazole Dosing:

• Loading dose: 800 mg (12 mg/kg), then 400 mg (6 mg/kg) daily 1
• Can be administered intravenously or orally 1

When to Choose Fluconazole:

• Mild to moderate illness (hemodynamically stable) 1
• No previous azole exposure 1
• Suspected C. albicans, C. tropicalis, or C. parapsilosis infection 1
• Specifically preferred for C. parapsilosis infections 1

Species-Specific Considerations

C. parapsilosis:

• Fluconazole is preferred over echinocandins due to decreased in vitro echinocandin activity 1
• If echinocandin was started empirically and patient is clinically improved with negative follow-up cultures, continuing the echinocandin is reasonable 1

C. glabrata:

• Echinocandin is strongly preferred 1
• Do not transition to fluconazole or voriconazole without confirmed susceptibility testing 1

C. krusei:

• Intrinsically resistant to fluconazole 1, 2
• Use echinocandin or voriconazole as step-down oral therapy 1

C. albicans:

• Most susceptible species 1
• Either fluconazole or echinocandin appropriate based on severity 1

Second-Line and Alternative Agents

Amphotericin B Formulations:

• Liposomal amphotericin B (L-AmB): 3-5 mg/kg daily 1
• Amphotericin B deoxycholate (AmB-d): 0.5-1.0 mg/kg daily 1
• Reserved for intolerance or limited availability of other agents 1
• Consider for persistent candidemia unresponsive to echinocandins 1

Voriconazole:

• Dosing: 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily 1
• Effective for candidemia but offers little advantage over fluconazole 1
• Recommended as step-down oral therapy for C. krusei or voriconazole-susceptible C. glabrata 1

Step-Down Therapy Strategy

Transition from echinocandin to fluconazole is recommended once the patient is clinically stable and the isolate is confirmed susceptible to fluconazole (e.g., C. albicans). 1

• Typically after 3-5 days of intravenous echinocandin therapy 1
• Requires documented clinical improvement 1
• Must have susceptibility confirmation 1

Duration of Therapy

Treatment should continue for 2 weeks after documented clearance of Candida from the bloodstream and resolution of symptoms. 1

• For candidemia without metastatic complications 1
• Longer duration required for deep-seated infections 1

Critical Adjunctive Measures

Central Venous Catheter Management:

• Catheter removal is strongly recommended for non-neutropenic patients with candidemia 1
• Early removal improves outcomes 1

Susceptibility Testing:

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

Common Pitfalls to Avoid

• Do not use fluconazole empirically in critically ill patients – echinocandins have superior outcomes in this population 1
• Do not assume all Candida species are fluconazole-susceptible – C. krusei is intrinsically resistant and C. glabrata often has reduced susceptibility 1, 2
• Do not delay initiation of antifungal therapy – early treatment is critical for reducing mortality 1
• Do not use topical agents for systemic candidiasis – they are ineffective 1
• Do not continue fluconazole in patients with suspected endocardial or CNS involvement – use fungicidal agents (amphotericin B or echinocandins) 1