Two Case Reports of Interferon-γ Therapy in Patients with Aspergillus Tracheobronchitis Who Developed an Immunocompromised State After Severe Abdominal Sepsis

BACKGROUND Aspergillus tracheobronchitis is a rare, high mortality condition typically seen in immunocompromised patients. Although commonly associated with classic immunocompromising conditions, such as immunosuppression due to chemotherapy or corticosteroids, or neutropenia, it can also develop in patients with sepsis-induced immunoparalysis, which is the term used to describe an immunocompromised state that results of imbalances in the inflammatory response in sepsis. Immunostimulatory therapy with interferon (IFN)-γ can be a viable treatment option in these cases. CASE REPORT We present 2 cases of patients without relevant medical history who developed severe abdominal sepsis. In the subsequent weeks, both patients developed several infectious complications, including invasive Aspergillus tracheobronchitis. Both patients exhibited signs of sepsis-induced immunoparalysis, including low monocytic human leukocyte antigen DR expression. In a novel treatment approach, we administered IFN-γ immunotherapy alongside standard antifungal treatment to address the underlying immunoparalysis. This combined therapy successfully cleared the Aspergillus infection in both patients. However, 1 patient died of respiratory failure due to an obstruction of necrotic tissue in the trachea 15 weeks after the start of IFN-γ treatment. CONCLUSIONS We hypothesize that a combination of sepsis-induced immunoparalysis and local ischemia of the trachea may have predisposed these patients to develop an invasive Aspergillus tracheobronchitis. This case series demonstrates the potential efficacy of immunostimulatory therapy with IFN-γ in treating opportunistic fungal infections in the context of sepsis-induced immunoparalysis. Our findings thereby underscore the importance of considering immunomodulatory approaches in managing complex infections in critically ill patients with acquired immune dysfunction.