Nebulized Amphotericin B in Mechanically Ventilated COVID-19 Patients to Prevent Invasive Pulmonary Aspergillosis: A Retrospective Cohort Study

IMPORTANCE: Despite high mortality rates of COVID-19-associated pulmonary aspergillosis (CAPA) in the ICU, antifungal prophylaxis remains a subject of debate. We initiated nebulized conventional amphotericin B (c-AmB) as antifungal prophylaxis in COVID-19 patients on invasive mechanical ventilation (IMV). OBJECTIVES: To assess the CAPA incidence in COVID-19 patients on IMV treated with and without nebulized c-AmB as antifungal prophylaxis. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of consecutive COVID-19 patients admitted to our adult 17-bed ICU in a university-affiliated general hospital in Ede, The Netherlands, between January 25, 2021, and July 9, 2021. Patients not requiring IMV or transferred from or to another ICU were excluded. From April 9, 2021, daily nebulized amphotericin B in all patients on IMV was initiated. MAIN OUTCOMES AND MEASURES: Bronchoscopy with bronchoalveolar lavage (BAL) was performed in case of positive cultures for Aspergillus from the respiratory tract and/or unexplained respiratory deterioration. Incidence of probable and proven CAPA was compared between patients treated with and without nebulized antifungal prophylaxis using Pearson chi-square test. RESULTS: A total of 39 intubated COVID-19 patients could be analyzed, of which 16 were treated with antifungal prophylaxis and 23 were not. Twenty-six patients underwent bronchoscopy with BAL. In patients treated with antifungal prophylaxis, the incidence of probable/proven CAPA was significantly lower when compared with no antifungal prophylaxis (27% vs 67%; p = 0.047). Incidence of tracheobronchial lesions and positive Aspergillus cultures and BAL-galactomannan was significantly lower in patients treated with antifungal prophylaxis (9% vs 47%; p = 0.040, 9% vs 53%; p = 0.044, and 20% vs 60%; p = 0.047, respectively). No treatment-related adverse events and no case of proven CAPA were encountered in patients receiving antifungal prophylaxis. CONCLUSIONS AND RELEVANCE: Nebulization of c-AmB in critically ill COVID-19 patients on IMV is safe and may be considered as antifungal prophylaxis to prevent CAPA. However, a randomized controlled trial to confirm this is warranted.