Weekly high-dose liposomal amphotericin B prevents invasive aspergillosis after heart transplantation.


Journal

Transplant infectious disease : an official journal of the Transplantation Society
ISSN: 1399-3062
Titre abrégé: Transpl Infect Dis
Pays: Denmark
ID NLM: 100883688

Informations de publication

Date de publication:
Dec 2021
Historique:
revised: 07 09 2021
received: 30 06 2021
accepted: 29 09 2021
pubmed: 18 10 2021
medline: 25 12 2021
entrez: 17 10 2021
Statut: ppublish

Résumé

Preventive strategies for invasive aspergillosis (IA) have still not been determined in heart transplant recipients whereas IA leads to a high mortality rate at 12 months posttransplantation. The use of voriconazole or echinocandins was proposed but can favor emergence of Aspergillus or Candida sp. resistant strains or promote neurological and liver disorders in some patients. To assess whether universal prophylaxis with weekly high-dose of liposomal amphotericin-B (L-AmB) can safely prevent IA in heart transplant recipients. Retrospective before/after study that included 142 patients who received heart transplantation between 2010 and 2019 at the University Hospital of Toulouse (France). Weekly high dose of L-AmB (7.5 mg/kg/week) was used as universal prophylaxis from 2016 because of high environmental exposure to Aspergillus sp. and high incidence of IA. Cumulative 1-year incidence of IA decreased from 23% to 5% after introduction of L-Amb prophylaxis. Multivariate analysis (Cox model) identified L-AmB prophylaxis as a protective factor against IA (hazard ratio [HR] 0.21 [95% confidence interval 0; 0.92], p = .04), whereas postoperative renal replacement therapy was associated with IA (HR 3.6 [95% confidence interval 1.38; 9.3], p = .001), after correction for confounding effects (induction regimen, methylprednisolone pulses and history of hematological malignancy). The incidence of acute kidney injury requiring renal replacement therapy was similar in the two groups, suggesting a low risk of kidney toxicity when L-AmB is used weekly. No patient developed severe kidney electrolyte loss nor L-AmB-related anaphylaxis. Once-weekly high-dose L-AmB is safe and may prevent the development of IA after heart transplantation.

Sections du résumé

BACKGROUND BACKGROUND
Preventive strategies for invasive aspergillosis (IA) have still not been determined in heart transplant recipients whereas IA leads to a high mortality rate at 12 months posttransplantation. The use of voriconazole or echinocandins was proposed but can favor emergence of Aspergillus or Candida sp. resistant strains or promote neurological and liver disorders in some patients.
OBJECTIVES OBJECTIVE
To assess whether universal prophylaxis with weekly high-dose of liposomal amphotericin-B (L-AmB) can safely prevent IA in heart transplant recipients.
PATIENTS/METHODS METHODS
Retrospective before/after study that included 142 patients who received heart transplantation between 2010 and 2019 at the University Hospital of Toulouse (France). Weekly high dose of L-AmB (7.5 mg/kg/week) was used as universal prophylaxis from 2016 because of high environmental exposure to Aspergillus sp. and high incidence of IA.
RESULTS RESULTS
Cumulative 1-year incidence of IA decreased from 23% to 5% after introduction of L-Amb prophylaxis. Multivariate analysis (Cox model) identified L-AmB prophylaxis as a protective factor against IA (hazard ratio [HR] 0.21 [95% confidence interval 0; 0.92], p = .04), whereas postoperative renal replacement therapy was associated with IA (HR 3.6 [95% confidence interval 1.38; 9.3], p = .001), after correction for confounding effects (induction regimen, methylprednisolone pulses and history of hematological malignancy). The incidence of acute kidney injury requiring renal replacement therapy was similar in the two groups, suggesting a low risk of kidney toxicity when L-AmB is used weekly. No patient developed severe kidney electrolyte loss nor L-AmB-related anaphylaxis.
CONCLUSIONS CONCLUSIONS
Once-weekly high-dose L-AmB is safe and may prevent the development of IA after heart transplantation.

Identifiants

pubmed: 34657372
doi: 10.1111/tid.13745
doi:

Substances chimiques

Antifungal Agents 0
liposomal amphotericin B 0
Amphotericin B 7XU7A7DROE

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e13745

Informations de copyright

© 2021 Wiley Periodicals LLC.

Références

Farges C, Cointault O, Murris M, et al. Outcomes of solid organ transplant recipients with invasive aspergillosis and other mold infections. Transpl Infect Dis. 2020;22(1):e13200.
Echenique IA, Angarone MP, Gordon RA, et al. Invasive fungal infection after heart transplantation: a 7-year, single-center experience. Transpl Infect Dis. 2017;19(1):e12650
Neofytos D, Chatzis O, Nasioudis D, et al. Epidemiology, risk factors and outcomes of invasive aspergillosis in solid organ transplant recipients in the Swiss Transplant Cohort Study. Transpl Infect Dis. 2018;20(4):e12898. https://doi.org/10.1111/tid.12898
Cook JC, Cook A, Tran RH, Chang PP, Rodgers JE. A case-control study of the risk factors for developing aspergillosis following cardiac transplant. Clin Transplant. 2018;32(9). https://doi.org/10.1111/ctr.13367
Coste AT, Kritikos A, Li J, et al. Emerging echinocandin-resistant Candida albicans and glabrata in Switzerland. Infection. 2020;48(5):761-766. https://doi.org/10.1007/s15010-020-01475-8
Youngs J, Low JM, Whitney L, et al. Safety and efficacy of intermittent high-dose liposomal amphotericin b antifungal prophylaxis in haemato-oncology: an eight-year single-centre experience and review of the literature. J Fungi. 2020;6(4):1-14. https://doi.org/10.3390/jof6040385
Luu Tran H, Mahmoudjafari Z, Rockey M, et al. Tolerability and outcome of once weekly liposomal amphotericin B for the prevention of invasive fungal infections in hematopoietic stem cell transplant patients with graft-versus-host disease. J Oncol Pharm Pract. 2016;22(2):228-234. https://doi.org/10.1177/1078155214560920
Cahuayme-Zuniga L, Lewis RE, Mulanovich VE, Kontoyiannis DP. Weekly liposomal amphotericin B as secondary prophylaxis for invasive fungal infections in patients with hematological malignancies. Med Mycol. 2012;50(5):543-548. https://doi.org/10.3109/13693786.2011.631152
Chaftari AM, Hachem RY, Ramos E, et al. Comparison of posaconazole versus weekly amphotericin B lipid complex for the prevention of invasive fungal infections in hematopoietic stem-cell transplantation. Transplantation. 2012;94(3):302-308. https://doi.org/10.1097/TP.0b013e3182577485
Giannella M, Ercolani G, Cristini F, et al. High-dose weekly liposomal amphotericin B antifungal prophylaxis in patients undergoing liver transplantation: A prospective phase II trial. Transplantation. 2015;99(4):848-854. https://doi.org/10.1097/TP.0000000000000393

Auteurs

Olivier Cointault (O)

Département de Néphrologie et Transplantation d'organes, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Marine Joly (M)

Département de Néphrologie et Transplantation d'organes, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Sophie Cassaing (S)

Laboratoire de Mycologie-Parasitologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

François Labaste (F)

Département d'Anesthésie et Réanimation, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Chloé Danet (C)

Service de Pharmacologie Clinique, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Lydie Porte (L)

Service des Maladie Infectieuses et Tropicales, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Joelle Guitard (J)

Département de Néphrologie et Transplantation d'organes, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Nassim Kamar (N)

Département de Néphrologie et Transplantation d'organes, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Université Paul Sabatier-Toulouse 3, Toulouse, France.
Institut National de la Santé et de la Recherche Médicale, U1043, IFR-BMT, Hôpital Purpan, Toulouse, France.

Stanislas Faguer (S)

Département de Néphrologie et Transplantation d'organes, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Département d'Anesthésie et Réanimation, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Institut National de la Santé et de la Recherche Médicale, UMR 1297, Institut des Maladies Métaboliques et Cardiovasculaires, Hôpital Rangueil, Toulouse, France.
Département de Néphrologie et Transplantation d'organes, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

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