Aspergillosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Haytham Allaham, M.D. [2]; Serge Korjian M.D.

Overview

Patients with allergic bronchopulmonary aspergillosis require antifungal pharmacotherapy, as well as oral steroids and optimization of asthma control. Patients with allergic Aspergillus rhinosinusitis require de-obstruction, nasal drainage, oral steroids, immunotherapy against allergens, and allergy control. Aspergilloma fungus ball usually requires surgical resection. Chronic pulmonary aspergillosis, invasive aspergillosis, and cutaneous aspergillosis may be treated with antifungal pharmacotherapy. Surgery may be required in severe cases of cutaneous aspergillosis for debridement or amputation.

Medical Therapy

Principles of Therapy

  • Patients with allergic bronchopulmonary aspergillosis require antifungal pharmacotherapy, as well as oral steroids and optimization of asthma control.
  • Patients with allergic Aspergillus rhinosinusitis require de-obstruction, nasal drainage, oral steroids, immunotherapy against allergens, and allergy control.
  • Aspergilloma fungus ball is usually not treated with antifungal agents unless there is bleeding into the lung tissue. In that case, surgery is required.
  • Chronic pulmonary aspergillosis usually requires systemic antifungal pharmacotherapy with or without intracavitary administration.
  • Invasive aspergillosis is treated with voriconazole for several weeks.
  • Cutaneous aspergillosis usually requires antifungal pharmacotherapy. Surgery may be required for debridement or amputation if pharmacotherapy alone is not helpful.

Antimicrobial Regimen

  • Aspergillosis[1]
  • 1. Invasive pulmonary aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • 2. Invasive sinus aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • 3. Tracheobronchial aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • 4. Chronic necrotizing pulmonary aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • 5. Aspergillosis of the CNS
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Note: There are drug interactions with anticonvulsant therapy.
  • 6. Aspergillus infections of the heart (endocarditis, pericarditis, and myocarditis)
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Note: endocardial lesions generally require surgical treatment. Aspergillus pericarditis usually requires pericardiectomy.
  • 7. Aspergillus osteomyelitis and septic arthritis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Note: Surgical resection of devitalized bone and cartilage is important for curative intent.
  • 8. Aspergillus infections of the eye (endophthalmitis and keratitis)
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Note: Topical therapy is indicated for keratitis, ophthalmologic intervention and management is recommended for all forms of ocular infection. Systemic therapy may be beneficial when treating aspergillus endophthalmitis.
  • 9. Cutaneous aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Note: Surgical resection is indicated when feasible.
  • 10. Aspergillus peritonitis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • 11. Prophylaxis against invasive aspergillosis
  • 12. Aspergilloma
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • 13. Chronic cavitary pulmonary aspergillosis
  • Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
  • Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
  • Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
  • Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
  • Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
  • Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (6): Micafungin 100–150 mg/day PO qd[2][1]
  • Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
  • Note: long-term therapy might be needed.
  • 14. Allergic bronchopulmonary Itraconazole aspergillosis
  • Preferred regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Alternative regimen (1): Voriconazole PO 200 mg bid
  • Alternative regimen (2): Posaconazole PO 400 mg bid
  • Note: Corticosteroids are a cornerstone of the therapy.
  • 15. Allergic aspergillus sinusitis
  • Preferred regimen: None or Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
  • Note: Few data available for other agents.
  • 16. Relative indications for surgical treatment of invasive aspergillosis
  • Pulmonary lesion in proximity to great vessels or pericardium
  • Pericardial infection
  • Invasion of chest wall from contiguous pulmonary lesion
  • Aspergillus empyema
  • Persistent hemoptysis from a single cavitary lesion
  • Infection of skin and soft tissues
  • Infected vascular catheters and prosthetic devices
  • Endocarditis
  • Osteomyelitis
  • Sinusitis
  • Cerebral lesions

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA; et al. (2008). "Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America". Clin Infect Dis. 46 (3): 327–60. doi:10.1086/525258. PMID 18177225.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G (2014). "Invasive fungal infections in the ICU: how to approach, how to treat". Molecules. 19 (1): 1085–119. doi:10.3390/molecules19011085. PMID 24445340.

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