What is the recommended antifungal treatment regimen for an immunosuppressed patient with suspected or proven candidiasis, including dosing for uncomplicated oral or esophageal thrush and for invasive disease?

Antifungal Treatment for Candidiasis in Immunosuppressed Patients

For invasive candidiasis in immunosuppressed patients, initiate an echinocandin immediately (caspofungin 70 mg loading dose then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg loading dose then 100 mg daily) as first-line therapy, continuing for at least 14 days after documented clearance of Candida from bloodstream and resolution of symptoms. 1

Invasive Candidiasis (Candidemia and Deep Tissue Infections)

First-Line Therapy

• Echinocandins are the preferred initial agents for invasive candidiasis in immunosuppressed patients, particularly those who are critically ill or have recent azole exposure 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

• Lipid formulation amphotericin B (3-5 mg/kg daily) is an alternative if echinocandin intolerance exists 1

Step-Down Therapy

• Transition to fluconazole 400 mg (6 mg/kg) daily after clinical improvement if the isolate is unlikely to be fluconazole-resistant and the patient is clinically stable 1

• Duration: Continue for 14 days after documented clearance of Candida from bloodstream and resolution of attributable symptoms 1

Critical Considerations for Neutropenic Patients

• For chronic disseminated candidiasis (hepatosplenic candidiasis) in neutropenic patients:

  • Initial therapy: Lipid formulation amphotericin B (3-5 mg/kg daily) OR echinocandin for several weeks 1
  • Step-down: Fluconazole 400 mg (6 mg/kg) daily for patients unlikely to have fluconazole-resistant isolates 1
  • Duration: Continue until lesions resolve on repeat imaging, typically several months 1

• Do not delay chemotherapy or hematopoietic cell transplantation due to chronic disseminated candidiasis; continue antifungal therapy throughout the high-risk period 1

Mucocutaneous Candidiasis

Oropharyngeal Candidiasis (Thrush)

Uncomplicated disease:

• Fluconazole 100-200 mg daily for 7-14 days 1
• Alternatives: Itraconazole 200 mg daily, nystatin suspension 200,000-400,000 units PO QID 1

Refractory or severe disease in immunosuppressed patients:

• Amphotericin B deoxycholate 0.3 mg/kg/day IV 1
• Echinocandin 1
• Voriconazole 1, 2

Esophageal Candidiasis

• Fluconazole 200-400 mg daily for 14-21 days until clinical improvement 1
• Minimum 14 days and at least 7 days following resolution of symptoms 3

Alternatives when fluconazole cannot be used:

• Itraconazole 200 mg daily PO 1
• Amphotericin B deoxycholate 0.3-0.7 mg/kg/day IV 1
• Echinocandin 1
• Voriconazole 2

CNS Candidiasis

• Amphotericin B deoxycholate 0.7-1 mg/kg with or without flucytosine is the preferred initial therapy 1
• Fluconazole 400-800 mg (6-12 mg/kg) daily for patients unable to tolerate amphotericin B 1
• Voriconazole can be used as step-down therapy in stable patients 1, 2
• Remove intraventricular devices 1
• Duration: Continue until all signs, symptoms, CSF abnormalities, and radiologic abnormalities resolve 1

Candida Endophthalmitis

• Multiple options available: Amphotericin B deoxycholate 0.7-1 mg/kg with flucytosine, fluconazole, lipid formulation amphotericin B, voriconazole, or echinocandin 1, 2
• Duration: At least 4-6 weeks, determined by repeated examinations to verify resolution 1, 2
• Surgical intervention required for severe endophthalmitis or vitreitis 1
• Diagnostic vitreal aspiration should be performed if etiology is unknown 1

Empiric Therapy in Critically Ill Immunosuppressed Patients

When to Initiate

• Start empiric antifungal therapy immediately in critically ill immunosuppressed patients with risk factors for invasive candidiasis, no other known cause of fever, and clinical signs of septic shock 1

Preferred Regimens

For nonneutropenic ICU patients:

• Echinocandin (preferred): Caspofungin 70 mg loading dose then 50 mg daily, anidulafungin 200 mg loading dose then 100 mg daily, or micafungin 100 mg daily 1
• Fluconazole 800 mg loading dose, then 400 mg daily is acceptable for patients without recent azole exposure and not colonized with azole-resistant Candida 1

Duration of empiric therapy:

• 2 weeks for patients who improve (same as documented candidemia) 1
• Consider stopping antifungal therapy if no clinical response at 4-5 days and no subsequent evidence of invasive candidiasis 1

Common Pitfalls to Avoid

• Never delay antifungal therapy in critically ill immunosuppressed patients with suspected invasive candidiasis—mortality increases with delayed treatment 4, 5

• Do not use fluconazole as initial therapy in critically ill patients, those with recent azole exposure, or those at risk for azole-resistant species 1

• Premature discontinuation leads to relapse—ensure adequate duration based on clearance of bloodstream infection and resolution of symptoms, not arbitrary time periods 1

• Do not use voriconazole for mucormycosis (zygomycosis)—amphotericin B formulations are mandatory 1, 2

• Always remove central venous catheters in candidemia when feasible 1

• Obtain imaging studies (CT or ultrasound of genitourinary tract, liver, spleen) if blood cultures remain persistently positive for Candida 1