10 years of prophylaxis with nebulized liposomal amphotericin B and the changing epidemiology of Aspergillus spp. infection in lung transplantation.
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.
Department of Infectious Diseases, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.|Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Maddalena
M
Peghin
Department of Pulmonology and Lung Transplant Unit, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.|Ciber Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Victor
V
Monforte
Department of Microbiology, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.
Maria-Teresa
MT
Martin-Gomez
Department of Infectious Diseases, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.|Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Isabel
I
Ruiz-Camps
Department of Pulmonology and Lung Transplant Unit, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.|Ciber Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Cristina
C
Berastegui
Department of Pulmonology and Lung Transplant Unit, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.|Ciber Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Berta
B
Saez
Department of Intensive Care Unit, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.
Jordi
J
Riera
Department of Pulmonology and Lung Transplant Unit, Hospital Puerta del Hierro, Madrid, Spain.
Piedad
P
Ussetti
Department of Thoracic Surgery, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.
Juan
J
Solé
Department of Infectious Diseases, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.|Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Joan
J
Gavaldá
Department of Pulmonology and Lung Transplant Unit, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.|Ciber Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Antonio
A
Roman
D000280:Administration, Inhalation; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage*; D001228:Aspergillosis / Q000517:prevention & control*; D001230:Aspergillus / Q000187:drug effects*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000382:microbiology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control; D011322:Primary Prevention / Q000379:methods; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
C068538:liposomal amphotericin B; D000666:Amphotericin B
antifungal prophylaxis; fungal infections; invasive aspergillosis; lung transplant; nebulized liposomal amphotericin B