Revista Iberoamericana de Micología

Revista Iberoamericana de Micología

Volume 33, Issue 4, October–December 2016, Pages 187-195
Revista Iberoamericana de Micología

Special article
EPICO 3.0. Antifungal prophylaxis in solid organ transplant recipientsEPICO 3.0. Profilaxis antifúngica en el paciente trasplantado de órgano sólido

https://doi.org/10.1016/j.riam.2016.02.001Get rights and content

Abstract

Background

Although over the past decade the management of invasive fungal infection has improved, considerable controversy persists regarding antifungal prophylaxis in solid organ transplant recipients.

Aims

To identify the key clinical knowledge and make by consensus the high level recommendations required for antifungal prophylaxis in solid organ transplant recipients.

Methods

Spanish prospective questionnaire, which measures consensus through the Delphi technique, was conducted anonymously and by e-mail with 30 national multidisciplinary experts, specialists in invasive fungal infections from six national scientific societies, including intensivists, anesthetists, microbiologists, pharmacologists and specialists in infectious diseases that responded to 12 questions prepared by the coordination group, after an exhaustive review of the literature in the last few years. The level of agreement achieved among experts in each of the categories should be equal to or greater than 70% in order to make a clinical recommendation. In a second term, after extracting the recommendations of the selected topics, a face-to-face meeting was held with more than 60 specialists who were asked to validate the pre-selected recommendations and derived algorithm.

Measurements and primary outcomes

Echinocandin antifungal prophylaxis should be considered in liver transplant with major risk factors (retransplantation, renal failure requiring dialysis after transplantation, pretransplant liver failure, not early reoperation, or MELD > 30); heart transplant with hemodialysis, and surgical re-exploration after transplantation; environmental colonization by Aspergillus, or cytomegalovirus (CMV) infection; and pancreas and intestinal transplant in case of acute graft rejection, hemodialysis, initial graft dysfunction, post-perfusion pancreatitis with anastomotic problems or need for laparotomy after transplantation. Antifungal fluconazole prophylaxis should be considered in liver transplant without major risk factors and MELD 20–30, split or living donor, choledochojejunostomy, increased transfusion requirements, renal failure without replacement therapy, early reoperation, or multifocal colonization or infection with Candida; intestinal and pancreas transplant with no risk factors for echinocandin treatment. Liposomal amphotericin B antifungal prophylaxis should be considered in lung transplant (inhalant form) and liver transplant with major risk factors. Antifungal prophylaxis with voriconazole should be considered in lung transplant, and heart transplant with hemodialysis, surgical re-exploration after transplantation, environmental colonization by Aspergillus, or CMV infection.

Conclusions

The management of antifungal prophylaxis in solid organ transplant recipients requires the application of knowledge and skills that are detailed in our recommendations and the algorithm developed therein. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their management and improve overall prognosis.

Resumen

Antecedentes

Aunque en la última década se ha observado una mejora en el tratamiento de la infección fúngica invasiva, todavía existen numerosas controversias en la profilaxis antifúngica del paciente trasplantado de órgano sólido.

Objetivos

Identificar los principales conocimientos clínicos y elaborar recomendaciones con un alto nivel de consenso, necesarias para la profilaxis antifúngica del paciente trasplantado de órgano sólido.

Métodos

Se realizó un cuestionario prospectivo español, que valora el consenso mediante la técnica Delphi. El cuestionario se llevó a cabo de forma anónima y por correo electrónico con 30 expertos multidisciplinarios nacionales, especialistas en infecciones fúngicas invasivas de seis sociedades científicas nacionales, que incluían intensivistas, anestesistas, microbiólogos, farmacólogos y especialistas en enfermedades infecciosas que respondieron a 12 preguntas preparadas por el grupo de coordinación, tras una revisión exhaustiva de la bibliografía de los últimos años. El nivel de acuerdo alcanzado entre los expertos en cada una de las categorías debía ser igual o superior al 70% para elaborar una recomendación. En un segundo término, después de extraer las recomendaciones de los temas seleccionados, se celebró una reunión presencial con más de 60 especialistas y se les solicitó la validación de las recomendaciones preseleccionadas y del algoritmo derivado de estas.

Mediciones y resultados principales

Debe considerarse la profilaxis antifúngica con equinocandinas en el trasplante hepático con los principales factores de riesgo (retrasplante, insuficiencia renal postrasplante con necesidad de diálisis, insuficiencia hepática pretrasplante, reintervención quirúrgica no precoz, o MELD > 30); trasplante cardíaco con hemodiálisis, y reexploración quirúrgica postrasplante; colonización ambiental por Aspergillus, o infección por citomegalovirus; trasplante de páncreas e intestino si existe rechazo agudo del injerto, hemodiálisis, disfunción inicial del injerto, problemas en la anastomosis con pancreatitis posperfusión, o necesidad de laparotomía postrasplante. Debe considerarse la profilaxis antifúngica con fluconazol en el trasplante hepático sin los principales factores de riesgo y MELD de 20-30, split o donante vivo, coledocoyeyunostomía, altos requerimientos transfusionales, fracaso renal sin necesidad de terapia sustitutiva, reintervención precoz o colonización multifocal o infección por Candida, y trasplante de páncreas e intestino sin factores de riesgo para el tratamiento con equinocandina. Debe considerarse la profilaxis antifúngica con anfotericina B liposómica en el trasplante pulmonar (vía inhalada) y el trasplante hepático con los principales factores de riesgo. Debe considerarse la profilaxis antifúngica con voriconazol en el trasplante pulmonar y el trasplante cardíaco con hemodiálisis, reexploración quirúrgica postrasplante, colonización ambiental por Aspergillus o enfermedad por citomegalovirus.

Conclusiones

El manejo de la profilaxis antifúngica del paciente trasplantado de órgano sólido requiere la aplicación de los conocimientos y destrezas que se detallan en nuestras recomendaciones y en el algoritmo desarrollado. Estas recomendaciones basadas en la metodología Delphi pueden ayudar a identificar a los potenciales pacientes, estandarizar su tratamiento en conjunto y mejorar su pronóstico.

Section snippets

1. Variables considered risk factors for the development of aspergillosis in liver transplant recipients

Answers provided by the coordinators: retransplant, the event of more than one acute rejection requiring the use of steroids or monoclonal antibodies during the first month, post-transplant renal failure, pretransplant fulminant liver failure, dialysis, poor graft function (basically primary graft failure), surgical reintervention, prior renal failure, severe bacterial infection requiring antibiotic therapy for more than 10 days, bile leak and/or primary hepaticojejustonomy, presence of

Recommendations and algorithm

Once the results achieved in the Delphi methodology regarding antifungal prophylaxis in solid organ transplant recipients were collected, five recommendations were elaborated and the conclusions are exhibited in Table 1. They are based on the questions which reached a consensus equal or higher than 70%. These recommendations and the algorithm deriving from them (Fig. 1) were validated thereafter during a face-to-face meeting with the hospital experts.

Conflict of interests

This consensus has been sponsored by MSD Laboratories, Spain.

Acknowledgements

We thank Carmen Romero and Ainhoa Torres (Entheos Editorial Group) for their excellent work and dedication to this project.

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