10 years of prophylaxis with nebulized liposomal amphotericin B and the changing epidemiology ofAspergillusspp. infection in lung transplantation

Abstract

Summary The aim of this study was to assess the outcome and tolerability of prophylactic nebulized liposomal amphotericin B (n‐LAB) in lung transplant recipients (LTR) and the changing epidemiology of Aspergillus spp. infection and colonization. We performed an observational study including consecutive LTR recipients (2003–2013) undergoing n‐LAB prophylaxis lifetime. A total of 412 patients were included (mean postoperative follow‐up 2.56 years; IQR 1.01–4.65). Fifty‐three (12.8%) patients developed 59 Aspergillus spp. infections, and 22 invasive aspergillosis (overall incidence 5.3%). Since 2009, person‐time incidence rates of Aspergillus spp. colonization and infection decreased (2003–2008, 0.19; 2009–2014, 0.09; P = 0.0007), but species with reduced susceptibility or resistance to amphotericin significantly increased (2003–2008, 38.1% vs 2009–2014, 58.1%; P = 0.039). Chronic lung allograft dysfunction (CLAD) was associated with Aspergillus spp. colonization and infection (HR 24.4, 95% CI 14.28–41.97; P = 0.00). Only 2.9% of patients presented adverse effects, and 1.7% required discontinuation. Long‐term administration of prophylaxis with n‐LAB has proved to be tolerable and can be used for preventing Aspergillus spp. infection in LTR. Over the last years, the incidence of Aspergillus spp. colonization and infection has decreased, but species with reduced amphotericin susceptibility or resistance are emerging. CLAD is associated with Aspergillus spp. colonization and infection.

Epidemiology and Immediate Indirect Effects of Respiratory Viruses in Lung Transplant Recipients: A 5-Year Prospective Study

“…infection (25). In our study, no statistical association was found, probably because of a statistical limitation related to a low incidence of aspergillosis secondary to an effective antifungal prophylaxis regimen (26).…”

Infectious Triggers of Chronic Lung Allograft Dysfunction

“…Accepting that at least small conidial Aspergillus colonization is a risk factor for subsequent CLAD, what can be done to reduce this risk? The use of life-long inhaled Ambisome has reduced the risk of both colonization and subsequent CLAD derived from Aspergillus in one study [51]. However, this was not definitively demonstrated in their study, in part because we do not know if in their pre-Ambisome era Aspergillus colonization was a risk factor for CLAD.…”

“…Contrary to the above studies, Peghin [51] recently published their single-center experience with life-long inhaled Ambisome prophylaxis against invasive fungal disease and did not find that Aspergillus colonization was a risk factor for CLAD in the over 400 LTR followed. Quite the opposite, they found that CLAD was a risk for Aspergillus colonization or infection (HR 24.4, CI .…”

Nebulized liposomal amphotericin prophylaxis in lung transplantation: shall we take it or leave it?

“…We read with interest the paper by Peghin et al [1] presenting the largest observational study on nebulized liposomal amphotericin B (n-LAB) as prophylaxis of aspergillosis in lung transplantation (LT). These authors adopted a lifelong approach with n-LAB administered at fixed dosage and frequency during the first 6 months and tapered thereafter.…”