Transplantation · 2026
Breakthrough Mold Infections During Long-term Nebulized Liposomal Amphotericin B Prophylaxis in Lung Transplant Recipients: A Single-center Cohort (NEBULA Study).
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Monforte Arnau, Los-Arcos Ibai, Martín-Gómez Maria Teresa, Berastegui Cristina, Márquez-Algaba Ester, Sacanell Judith, Rosado Joel, Falcó-Roget Anna, Escudero Gonzalo, Casanovas Jose, Kirkegaard-Biosca Cristina, Sáez-Giménez Berta, Monforte Victor, Gavaldà Joan, Len Oscar
Аннотация
BACKGROUND: Aspergillus spp. and other mold infections are the most common fungal infections in lung transplant recipients (LTRs). There is no established antifungal preventive strategy for LTR; however, lifelong nebulized liposomal amphotericin B (n-LAB) prophylaxis has been used in our center. This study evaluated breakthrough mold infections (b-MIs) and the tolerability of n-LAB prophylaxis in a LTR cohort.
METHODS: This observational retrospective study included all consecutive adult LTR who received n-LAB prophylaxis between August 2013 and March 2023. Participants were followed up for at least 1-y posttransplant unless they died earlier. Only proven and probable mold infections during n-LAB exposure were included in the study.
RESULTS: Among 802 LTR (median age, 57.8 y; 41.9% female), 821 transplants were performed. The incidence of b-MI within the first year posttransplantation was 8.7%. Over a median follow-up of 2.56 y (interquartile range, 1.01-5.25 y), 94 LTR (11.7%) developed b-MI, comprising 111 episodes of infection. Independent risk factors for b-MI included bronchial stenosis, bronchial stent placement, and single lung transplant. Prophylaxis with n-LAB was well tolerated, with discontinuation owing to adverse events occurring in only 18 participants (2.2%). Mold colonization and b-MI were both associated with an increased risk of death (adjusted hazard ratio, 5.38; 95% confidence interval, 3.24-8.94 and adjusted hazard ratio, 14.07; 95% confidence interval, 8.50-23.28, respectively). No difference in mortality was observed between the amphotericin B-nonsusceptible isolates.
CONCLUSIONS: Lifelong n-LAB prophylaxis was associated with a low incidence of mold infection during prolonged follow-up and maintained excellent tolerability. The emergence of amphotericin B-nonsusceptible molds was not associated with increased mortality.
METHODS: This observational retrospective study included all consecutive adult LTR who received n-LAB prophylaxis between August 2013 and March 2023. Participants were followed up for at least 1-y posttransplant unless they died earlier. Only proven and probable mold infections during n-LAB exposure were included in the study.
RESULTS: Among 802 LTR (median age, 57.8 y; 41.9% female), 821 transplants were performed. The incidence of b-MI within the first year posttransplantation was 8.7%. Over a median follow-up of 2.56 y (interquartile range, 1.01-5.25 y), 94 LTR (11.7%) developed b-MI, comprising 111 episodes of infection. Independent risk factors for b-MI included bronchial stenosis, bronchial stent placement, and single lung transplant. Prophylaxis with n-LAB was well tolerated, with discontinuation owing to adverse events occurring in only 18 participants (2.2%). Mold colonization and b-MI were both associated with an increased risk of death (adjusted hazard ratio, 5.38; 95% confidence interval, 3.24-8.94 and adjusted hazard ratio, 14.07; 95% confidence interval, 8.50-23.28, respectively). No difference in mortality was observed between the amphotericin B-nonsusceptible isolates.
CONCLUSIONS: Lifelong n-LAB prophylaxis was associated with a low incidence of mold infection during prolonged follow-up and maintained excellent tolerability. The emergence of amphotericin B-nonsusceptible molds was not associated with increased mortality.