How do we treat Invasive Aspergillosis?

The CT scan is reviewed and the medical team take advice from a local Infection specialist. It is felt that, taking into account the patient’s CT findings, neutropenia, symptoms and limited response to antibiotics, that antifungal treatment for invasive aspergillosis is indicated.

The patient is planned for bronchoscopy in 48 hours. Serum galactomannan and β-1-3-D-glucan are awaited. Empirical antifungal therapy is started.

Consider the potential stewardship issues that arise from this case:

• Is there anything about the management you would modify so far?
• What additional information would you want from the patient?
• When do you plan to review this treatment for its effectiveness and appropriateness?

The management of invasive aspergillosis has been studied in a wide variety of patients. The majority of international guidelines recommend voriconazole as the first line treatment for IA. This is usually given intravenously as the patient is often very unwell, and/or may be unable to absorb the oral preparation.

In cases of voriconazole intolerance or resistance, the second line agent is isavuconazole. This is another azole antifungal which has comparable efficacy. It is also given intravenously at the beginning of therapy.

Some patients are intolerant to all azoles or their Aspergillus isolates are resistant to them. In these cases, liposomal amphotericin B is an alternative. Also, liposomal amphotericin B is the first line choice for patients who developed an infection whilst on azole antifungal prophylaxis. Amphotericin B is only available intravenously and is associated with a significant risk for renal toxicity, particularly if not administered exactly according to the manufacturer’s instructions.

Beyond antifungals

Many patients with IA have multiple risk factors for disease. Consider the main risk factors we have covered.

For some patients, an important part of managing their IA is improving host defences. Reduction of the dose of steroids and other immunosuppressive medications, or addition of hematopoietic growth factors may be required in order to fully manage the infection.

Aspergillus is angiotrophic and invades blood vessels and causes thrombosis. Some patients will go on to develop life-threatening haemoptysis. When large vessels are invaded and rupture, patients can die from the ensuing bleeding. Aside from antifungal treatment, the recommended treatment for this bleeding is bronchial artery embolisation.

Below is an image of a Bronchial arteriogram which shows the right bronchial artery before and after embolization

Refractory disease, especially in the context of antifungal resistance, will occasionally require more than medical treatment. While the risk is high, some patients may require surgical treatment. This is usually wedge-resection or lobectomy in pulmonary disease.

The below image is of a post-mortem lung section. The pale circle on the left hand side of the lung is a ball of fungus (likely Aspergillus). Note the area of haemorrhage around the infection.