Inhaled amphotericin B lipid complex for prophylaxis against COVID-19-associated invasive pulmonary aspergillosis.

Dear Editor,

Recently, Prattes and colleagues [1] published in Intensive Care Medicine a high incidence of coronavirus disease 2019-associated invasive pulmonary aspergillosis (CAPA), according to 2020 ECMM/ISHAM consensus criteria [2], with a correspondingly high mortality rate. However, both the guidelines and a Taskforce report published recently [3] only considered host risk factors [3]. Many work-related aspergillosis outbreaks have been reported due to airborne contamination with Aspergillus spores [4]. Protective measures against environmental contamination must be taken when there is construction activity on-site in a hospital. Antifungal prophylaxis is not recommended in mechanical ventilated patients affected by coronavirus disease 2019 (COVID-19) [3].

We implemented an active surveillance protocol for CAPA in mechanically ventilated patients with COVID-19 admitted to the intensive care unit (ICU). The protocol consisted of weekly assessment of galactomannan (GM), fungal culture, and calcofluor white microscopy from endotracheal aspirate for all patients. If test results were positive (GM cutoff > 0.9) or the patient suffered respiratory deterioration, a bronchoscopy with bronchoalveolar lavage (BAL) was performed. CAPA case definition utilized was in accordance with ECMM/ISHAM consensus criteria [2].

In April 2021, there was a CAPA outbreak within the ICU which was associated with remodeling carried out one floor below, despite protection measures having been implemented. Eleven patients developed CAPA in 3 weeks, which represented an incidence of 22.4% (11/49). The predominant microbiological diagnostic tool was a BAL GM, which was positive in 90% of patients. In 72%, both culture and BAL GM were positive. Air environmental measurements were performed and levels higher than 10 cfu/m3 were considered positive.

In response to the outbreak, protective measures were intensified. All mechanically ventilated patients received 50 mg every 48 h of inhaled amphotericin B lipid complex (ABLC). The isolation rooms were cleaned and closed, and additional cleaning of workspaces and hallways was performed, with special emphasis on architectural isolation of the renovation work. Despite the persistence of airborne Aspergillus contamination during 34 consecutive days, no patient who received ABLC developed CAPA (Fig. 1). Interestingly, only two patients with bronchospasm, who did not receive ABCL, developed CAPA. The patients’ characteristics, ICU pressure, and treatment over time did not change. A total of 45 patients received prophylaxis with inhaled ABLC. Of these, four (8.8%) suffered bronchospasm and in one patient, the effect was severe enough that a determination was made to suspend the prophylaxis. An additional 33.3% (15/45) experienced mechanical problems due to the buildup of the drug in the filter of the expiratory limb of the ventilator, but in all cases the issue was able to be solved by the nursing staff and caused no clinical impact on the patients.

Fig. 1

CAPA diagnosis from August 2020 to June 2021

We conclude that the application of a set of increased environmental protective measures and supplementary inhaled ABCL should be considered to control an outbreak of CAPA in mechanically ventilated patients with COVID-19. We agree with Koehler and colleagues [2], who suggest that the reported excess mortality might justify antifungal prophylaxis trials, similar to those proposed for patients with invasive aspergillosis [5]. Therefore, inhaled antifungal prophylaxis may be an effective option to reduce CAPA when its incidence is elevated.