What is the treatment for invasive Aspergillosis?

Treatment of Invasive Aspergillosis

Voriconazole is recommended as the first-line treatment for invasive aspergillosis in most patients due to its superior efficacy and survival outcomes compared to other antifungal agents. 1

Primary Treatment Options

• Voriconazole is the drug of choice for primary treatment of invasive aspergillosis with strong evidence supporting its use (A-I level recommendation) 1
• Dosing regimen for voriconazole:
  • Loading dose: 6 mg/kg IV every 12 hours for 1 day
  • Maintenance dose: 4 mg/kg IV every 12 hours or 200 mg oral twice daily 1
• Liposomal amphotericin B (L-AMB) at 3-5 mg/kg/day IV can be considered as alternative primary therapy in patients who cannot tolerate voriconazole (A-I) 1
• Isavuconazole is also FDA-approved as a first-line therapy option for invasive aspergillosis 2, 3
  • Loading dose: 200 mg every 8 hours for 6 doses (first 48 hours)
  • Maintenance dose: 200 mg once daily 2, 3

Salvage Therapy Options

For patients who fail primary therapy or cannot tolerate initial treatment, several options exist:

• Lipid formulations of amphotericin B (LFAB) (A-II) 1
• Posaconazole (B-II) - recently shown to be non-inferior to voriconazole in a phase 3 trial 1, 4
• Itraconazole (B-II) 1
• Caspofungin (B-II) 1
• Micafungin (B-II) 1

Treatment Approach Algorithm

1. Confirm diagnosis while initiating therapy (early treatment is critical) 1
2. Start primary therapy with voriconazole or isavuconazole 1, 2
3. Monitor response through clinical evaluation and radiographic imaging (CT scans) at regular intervals 1
4. Adjust therapy if inadequate response:
   • Change to a different drug class (B-II) 1
   • Consider combination therapy in refractory cases (B-II) 1

Duration of Treatment

• Treatment should continue for a minimum of 6-12 weeks 1, 2
• In immunosuppressed patients, therapy should be continued throughout the period of immunosuppression and until lesions have resolved 1
• Long-term therapy is facilitated by the availability of oral voriconazole 1

Special Considerations

• Aspergillus terreus is clinically resistant to amphotericin B, necessitating azole therapy 1
• For patients with successfully treated invasive aspergillosis who will require subsequent immunosuppression, resumption of antifungal therapy can prevent recurrent infection (A-III) 1
• Therapeutic drug monitoring should be considered for azoles, particularly in cases of treatment failure 1
• Combination therapy is not routinely recommended for primary treatment (B-II) but may be considered for salvage therapy 1

Common Pitfalls and Caveats

• Deoxycholate amphotericin B (D-AMB) is not recommended as primary therapy due to inferior outcomes and significant toxicity compared to voriconazole (A-I) 1, 5
• Visual disturbances are common with voriconazole (occurring in approximately 30-45% of patients) but are typically transient 6, 7
• Drug interactions are significant with azoles and require careful medication review 8
• Species identification is important as some Aspergillus species have intrinsic resistance to certain antifungals 1
• Breakthrough invasive aspergillosis during mold-active azole prophylaxis should be treated with a different drug class 1