What is the recommended treatment for a patient with a resistant Candida infection, considering their medical history and potential immunocompromised status?

Treatment of Resistant Candida Infections

For fluconazole-resistant Candida species, an echinocandin (caspofungin, micafungin, or anidulafungin) is the recommended first-line therapy, with lipid formulation amphotericin B reserved as an alternative for echinocandin-resistant or intolerant cases. 1

Initial Therapy Selection Based on Resistance Pattern

For Azole-Resistant Species (C. glabrata, C. krusei)

• Echinocandins are the preferred first-line agents for fluconazole-resistant Candida species 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 recommended when there is suspected azole- and echinocandin-resistance, or intolerance to echinocandins 1

• For C. krusei specifically, an echinocandin, lipid formulation amphotericin B, or voriconazole are all appropriate options 1

For Refractory Oropharyngeal/Esophageal Candidiasis

When fluconazole-resistant oropharyngeal or esophageal candidiasis occurs (particularly in HIV/AIDS patients):

• Posaconazole 400 mg twice daily is strongly recommended 1
• Itraconazole oral solution (≥200 mg/day) is an alternative 1
• Voriconazole 200 mg twice daily can be considered 1
• Any echinocandin is appropriate, though parenteral administration limits use for mucosal disease 1

Species-Specific Considerations

C. glabrata Management

• Transition to higher-dose fluconazole (800 mg daily) or voriconazole (200-300 mg twice daily) should only occur if susceptibility testing confirms susceptibility to these agents 1
• Echinocandins remain preferred given the high rates of azole resistance in this species 1

C. auris Management

• Echinocandins are recommended as first-line therapy for C. auris infections 1
• Liposomal amphotericin B or amphotericin B deoxycholate may be considered for persistent candidemia or clinical unresponsiveness to echinocandins without evidence of amphotericin B resistance 1

C. lusitaniae Management

• Fluconazole (6 mg/kg per day, approximately 400 mg daily) is the preferred therapy due to this species' unique susceptibility pattern and characteristic resistance to amphotericin B 2
• Higher doses (12 mg/kg per day or 800 mg daily) may be considered for dose-dependent susceptibility 2

Critical Management Steps

Susceptibility Testing

• Antifungal susceptibility testing should be performed when there is treatment failure or prior antifungal exposure 1, 2
• Testing for azole susceptibility is recommended for all bloodstream and clinically relevant Candida isolates 1

Duration of Therapy

• Minimum 14 days after documented clearance of Candida from bloodstream and resolution of symptoms for candidemia without metastatic complications 1
• Treatment duration for C. lusitaniae should be at least 14 days after the last positive blood culture and resolution of signs and symptoms 2

Source Control

• Central venous catheters should be removed as early as possible when the CVC is the presumed source and can be safely removed 1
• Follow-up blood cultures every 48-72 hours are essential to document clearance 1

Important Caveats

• Amphotericin B deoxycholate is not recommended as initial therapy due to toxicity, though lipid formulations are acceptable alternatives 1
• Monotherapy with flucytosine should be avoided as resistance develops rapidly 1
• Cross-resistance between fluconazole and itraconazole occurs in approximately 30% of fluconazole-resistant isolates 1
• Voriconazole offers little advantage over fluconazole as initial therapy for candidemia but is useful as step-down therapy for C. krusei 1, 3
• Posaconazole is the only azole with activity against zygomycetes, which may be relevant in mixed infections 4