What are the treatment options for aspergillosis?

Treatment Options for Aspergillosis

Voriconazole is the first-line treatment for invasive aspergillosis due to its superior efficacy and survival outcomes compared to other antifungal agents. 1, 2

Primary Treatment Options

First-Line Therapy

• Voriconazole is recommended as the primary treatment for invasive aspergillosis in most patients with strong evidence supporting its use (A-I level recommendation) 1, 2
• Dosing regimen: 6 mg/kg IV every 12 hours for 1 day (loading dose), followed by 4 mg/kg IV every 12 hours or 200 mg oral twice daily for maintenance 2, 3
• Oral therapy can be maximized by using a dose of 4 mg/kg rounded up to convenient pill sizes 1
• For seriously ill patients, the parenteral formulation is recommended 1

Alternative First-Line Options

• Liposomal amphotericin B (L-AMB) at 3-5 mg/kg/day IV is an alternative primary therapy for patients who cannot tolerate voriconazole (A-I recommendation) 1, 2
• A randomized trial comparing two doses of liposomal amphotericin B showed similar efficacy in both arms, supporting its use as alternative primary therapy 1
• Isavuconazole is another alternative first-line agent with comparable efficacy to voriconazole 2, 4

Salvage Therapy Options

• For patients failing primary therapy, options include:
  • Lipid formulations of amphotericin B (LFAB) (A-II recommendation) 1, 2
  • Posaconazole (B-II recommendation) 1, 2
  • Itraconazole (B-II recommendation) 1, 2
  • Caspofungin (B-II recommendation) 1, 2
  • Micafungin (B-II recommendation) 1, 2
• Refractory infection may respond to a change to another drug class (B-II) or to a combination of agents (B-II) 1
• Therapeutic options for patients whose aspergillosis is refractory to voriconazole include changing to an amphotericin B formulation or an echinocandin 1

Site-Specific Treatment Recommendations

CNS Aspergillosis

• Voriconazole is the primary recommendation for systemic antifungal therapy of CNS aspergillosis (A-II) 1
• Itraconazole, posaconazole, or lipid formulations of amphotericin B are recommended for patients intolerant or refractory to voriconazole (B-III) 1
• Surgical resection of lesions may be definitive treatment and prevent serious neurological sequelae 1
• Avoid corticosteroids as they may be deleterious (C-III) 1
• Intrathecal or intralesional antifungal therapy is not recommended (B-III) 1

Sinus Aspergillosis

• Both surgery and either systemic voriconazole or a lipid formulation of amphotericin B are recommended for invasive Aspergillus fungal sinusitis 1
• Surgical removal alone can be used to treat Aspergillus fungal ball of the paranasal sinus 1
• Early recognition and therapeutic intervention with systemic antifungal therapy and surgical resection/debridement is important 1

Other Forms of Aspergillosis

• Aspergillus endocarditis: Early surgical intervention combined with antifungal therapy (voriconazole or lipid formulation of amphotericin B) is recommended 1
• Aspergillus osteomyelitis and arthritis: Surgical intervention where feasible, combined with voriconazole 1
• Cutaneous aspergillosis: Treatment with voriconazole in addition to evaluation for a primary focus of infection 1
• Aspergillus peritonitis: Prompt peritoneal dialysis catheter removal accompanied by systemic voriconazole therapy 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 in stable patients 1

Monitoring Response to Treatment

• Serial clinical evaluation of all symptoms and signs 1
• Radiographic imaging, usually with CT, at regular intervals 1
• The volume of pulmonary infiltrates may increase for the first 7-10 days of therapy, especially during granulocyte recovery 1
• Serial serum galactomannan assays can be used for monitoring, though this remains investigational 1
• Progressive increase in Aspergillus antigen levels over time signifies a poor prognosis 1

Common Pitfalls to Avoid

• Delaying antifungal therapy while awaiting diagnostic confirmation can worsen outcomes in high-risk patients 2, 4
• Using echinocandins as primary monotherapy is not recommended due to inferior efficacy compared to voriconazole 2, 4
• Failing to monitor drug levels for azole antifungals can lead to suboptimal treatment outcomes or toxicity 2, 4
• Misinterpreting radiological progression shortly after treatment initiation or following neutrophil recovery as treatment failure 4
• For patients on azole therapy, drug interactions must be carefully monitored as they can significantly affect treatment efficacy 5, 6

Prophylaxis

• Antifungal prophylaxis with posaconazole is recommended in:
  • HSCT recipients with graft-versus-host disease (GVHD) who are at high risk for invasive aspergillosis 1
  • Neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome who are at high risk for invasive aspergillosis (A-I) 1, 7