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

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Introduction

Direct damage to airway epithelium and immune dysregulation in severe viral pneumonia along with treatment with immunosuppressive agents is known to cause increased susceptibility to fungal superinfections, such as invasive pulmonary aspergillosis (IPA). Similar to influenza-associated pulmonary aspergillosis (IAPA), COVID-19-associated pulmonary aspergillosis (CAPA) is known to have a nearly two-fold mortality rate compared with the critically ill without pulmonary aspergillosis.

Therefore, prompt diagnostic work-up followed by antifungal therapy is recommended in COVID-19 patients on invasive mechanical ventilation (IMV) with unexplained respiratory deterioration or positive Aspergillus culture from the respiratory tract. A potentially increasing CAPA incidence together with an associated increased mortality and its diagnostic challenges may justify a prophylactic approach to prevent at risk COVID-19 patients to develop CAPA. The objective of this study was to assess the CAPA incidence among COVID-19 patients on IMV treated with and without nebulized c-AmB.

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.

Conclusion

In critically ill COVID-19 patients on IMV, nebulizing c-AmB is safe and could be used as antifungal prophylaxis to prevent CAPA. However, a randomized controlled trial to confirm this is warranted.

Source:  Source – Melchers M, van Zanten ARH, Heusinkveld M, Leeuwis JW, Schellaars R, Lammers HJW, Kreemer FJ, Haas PJ, Verweij PE, van Bree SHW. 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. PMID: 35558738; PMCID: PMC9088229.