What are the first-line treatments for common fungal infections in immunocompromised patients?

First-Line Treatments for Common Fungal Infections in Immunocompromised Patients

For immunocompromised patients with fungal infections, voriconazole is the first-line treatment for invasive aspergillosis, amphotericin B plus fluconazole for cryptococcal CNS/disseminated disease, and fluconazole for invasive candidiasis. 1

Invasive Aspergillosis

First-line treatment:

• Voriconazole (Strong recommendation, High-quality evidence) 1
  • Loading dose: 400 mg (6 mg/kg) every 12 hours for two doses on Day 1
  • Maintenance: 200 mg (3-4 mg/kg) twice daily 1
  • Treatment duration: Minimum 6-12 weeks 1

Alternative treatments:

• Liposomal Amphotericin B (L-AmB): 3-5 mg/kg daily 1
  • Use when voriconazole is contraindicated or not tolerated
• Isavuconazole: Shows excellent efficacy in recent studies 2
• Posaconazole: Effective for prophylaxis and treatment 3, 4

Special considerations:

• Surgical intervention recommended for:
  • Pulmonary lesions near great vessels or pericardium
  • Chest wall invasion
  • Emphysema
  • Persistent hemoptysis from a single cavitary lesion 1
• Echinocandins are not recommended as primary monotherapy 1

Cryptococcal Infections

CNS or Disseminated Disease:

• First-line treatment:
  • Amphotericin B deoxycholate (AmB-d) (0.7-1.0 mg/kg/day) plus fluconazole for 10-12 weeks 1
  • Alternative: Liposomal Amphotericin B (L-AmB) for 6-10 weeks (4-6 mg/kg/day) 1

Management of elevated intracranial pressure:

• If CSF opening pressure ≥250 mmH₂O: Serial lumbar drainage to achieve closing pressure <200 mmH₂O
• If CSF opening pressure <200 mmH₂O: Initiate medical therapy and follow up with lumbar puncture at second week 1

Pulmonary cryptococcosis:

• For immunocompetent patients: Fluconazole 200-400 mg/day PO
• For immunocompromised patients: Treat as disseminated infection 1

Invasive Candidiasis

First-line treatment:

• Fluconazole 1
  • Loading: 800 mg (12 mg/kg) on Day 1
  • Maintenance: 400 mg (6 mg/kg) daily

Alternative treatments:

• Echinocandins:
  • Caspofungin: 70 mg loading, then 50 mg daily
  • Micafungin: 100 mg daily
  • Anidulafungin: 200 mg loading, then 100 mg daily 1
• Amphotericin B deoxycholate: 0.5-1.0 mg/kg/day 1

Prophylaxis:

• Fluconazole: For high-risk patients (HSCT recipients, solid organ transplant recipients) 1
• Nystatin: For leukemic patients during chemotherapy 1

Invasive Zygomycosis (Mucormycosis)

First-line treatment:

• Liposomal Amphotericin B (3-10 mg/kg/day) 1
• Surgical resection of infected tissue is mandatory 1

Clinical Pearls and Pitfalls

Important considerations:

1. Diagnostic testing is crucial before initiating therapy:

   • Galactomannan antigen in serum/BAL for aspergillosis
   • Cryptococcal antigen in serum for cryptococcosis
   • Histoplasma antigen in urine for histoplasmosis
   • Coccidioides antibody for Valley Fever

2. Drug interactions:

   • Triazoles have significant drug interactions, especially with anticonvulsants 1
   • Monitor for hepatotoxicity with voriconazole

3. Treatment failure management:

   • Review evidence of infection
   • Test antifungal susceptibility
   • Review potential interacting drugs
   • Consider therapeutic drug monitoring
   • Reduce immunosuppression if feasible
   • Consider surgical intervention
   • Switch to different class or combination therapy 1

4. Secondary prophylaxis:

   • For patients with successfully treated invasive aspergillosis who require subsequent immunosuppression 1
   • For AIDS patients with cryptococcosis: fluconazole 200 mg/day until CD4 >100/μL and undetectable HIV viral load for 3 months 1

5. Environmental control:

   • Hospitalized allogeneic HSCT recipients should be placed in a protected environment
   • Educate patients about precautions to reduce mold exposure 1, 5