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

Max Melchers; Arthur R H van Zanten; Moniek Heusinkveld; Jan Willem Leeuwis; Roel Schellaars; Hendrick J W Lammers; Freek J Kreemer; Pieter-Jan Haas; Paul E Verweij; Sjoerd H W van Bree

doi:10.1097/CCE.0000000000000696

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

Crit Care Explor. 2022 May 9;4(5):e0696. doi: 10.1097/CCE.0000000000000696. eCollection 2022 May.

Authors

Affiliations

¹ Department of Intensive Care Medicine, Gelderse Vallei Hospital, Ede, The Netherlands.
² Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
³ Department of Medical Microbiology, Gelderse Vallei Hospital, Ede, The Netherlands.
⁴ Department of Pathology, Rijnstate Hospital, Arnhem, The Netherlands.
⁵ Department of Pharmacy, Gelderse Vallei Hospital, Ede, The Netherlands.
⁶ Department of Pulmonary Medicine, Gelderse Vallei Hospital, Ede, The Netherlands.
⁷ Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁸ Department of Medical Microbiology and Radboudumc-CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract

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.

Keywords: Aspergillus; COVID-19; amphotericin B; antibiotic prophylaxis; intensive care unit; invasive pulmonary aspergillosis.