What is Aspergillus (a type of fungus) infection?

From the Guidelines

Invasive aspergillosis should be treated with voriconazole as the first-line therapy, at doses of 6 mg/kg IV twice daily on day 1, followed by 4 mg/kg twice daily, as recommended by the Infectious Diseases Society of America (IDSA) guidelines 1. Aspergillus is a genus of mold fungi that can cause several types of health problems, including allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, and invasive aspergillosis. The most severe form, invasive aspergillosis, primarily affects severely immunocompromised patients, such as those with prolonged neutropenia, allogeneic hematopoietic stem cell transplant (HSCT), solid organ transplant (SOT), inherited or acquired immunodeficiencies, corticosteroid use, and others.

Key Considerations

• The IDSA guidelines emphasize the importance of early diagnosis and treatment of invasive aspergillosis to improve outcomes 1.
• Voriconazole is the preferred treatment due to its broad spectrum of activity and high efficacy in treating invasive aspergillosis 1.
• Treatment duration varies from weeks to months depending on the condition and patient response.
• Prevention focuses on reducing exposure to mold in high-risk individuals through HEPA filters and avoiding activities that disturb soil or dust.

Management of Aspergillosis

• The IDSA guidelines provide recommendations for the management of different forms of aspergillosis, including invasive aspergillosis, chronic and saprophytic forms, and allergic forms 1.
• The guidelines are based on a systematic review of the literature and use the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to evaluate the strength of the recommendations and the quality of the evidence 1.

From the FDA Drug Label

Antimicrobial Activity Isavuconazole has activity against most strains of the following microorganisms, both in vitro and in clinical infections: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucorales such as Rhizopus oryzae and Mucormycetes species In this trial, the protocol-defined maximum treatment duration was 84 days. Mean treatment duration was 47 days for both treatment groups, of which 8 to 9 days was by an intravenous route of administration. All-cause mortality through Day 42 in the overall population (ITT) was 18.6% in the CRESEMBA treatment group and 20. 2% in the voriconazole treatment group for an adjusted treatment difference of -1.0% with 95% confidence interval of -8.0% to 5. 9%. Overall success at End-of-Treatment (EOT) was assessed by a blinded, independent Data Review Committee (DRC) using pre-specified clinical, mycological, and radiological criteria. In the subgroup of patients with proven or probable invasive aspergillosis confirmed by serology, culture or histology, overall success at EOT was seen in 35% of CRESEMBA-treated patients compared to 38. 9% of voriconazole-treated patients

• Aspergillus Treatment: Isavuconazole has shown activity against Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger.
• Mortality Rate: The all-cause mortality rate through Day 42 was 18.6% for CRESEMBA and 20.2% for voriconazole.
• Success Rate: The overall success rate at End-of-Treatment (EOT) was 35% for CRESEMBA-treated patients and 38.9% for voriconazole-treated patients with proven or probable invasive aspergillosis. 2

From the Research

Aspergillus Overview

• Aspergillus is a type of fungus that can cause invasive aspergillosis, a life-threatening infection in immunocompromised patients 3, 4.
• The disease is caused mainly by Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger, with other species being less prevalent 3.

Treatment of Invasive Aspergillosis

• Voriconazole is currently the drug of choice for the treatment of invasive aspergillosis, with a response rate of 52.8% compared to 31.6% for amphotericin B 5, 6.
• Voriconazole has been shown to be better tolerated than amphotericin B, with fewer treatment-related adverse events and serious adverse events 5, 6.
• Liposomal amphotericin B is also effective in the treatment of invasive aspergillosis, with a response rate similar to voriconazole 3.
• Combination therapy with antifungal agents has been introduced in clinical trials, but no significant benefit has been obtained compared to voriconazole alone 4.

Management of Voriconazole-Refractory Invasive Aspergillosis

• Voriconazole-refractory invasive aspergillosis can be caused by various factors, including misdiagnosis, co-infection with another mold, inadequate blood voriconazole levels, and infection with voriconazole-resistant Aspergillus 7.
• Management of voriconazole-refractory invasive aspergillosis requires sequential tests to determine the appropriate treatment, including medical treatment or surgical intervention, adjustment of voriconazole dose, and monitoring of serum galactomannan levels 7.

Prophylaxis and Early Diagnosis

• Prophylaxis of invasive aspergillosis is important, especially in high-risk populations, but most efforts have failed to demonstrate survival advantages 4.
• Early diagnosis and treatment of invasive aspergillosis are crucial for successful management, with the introduction of non-culture based tools being an important step forward 4.