Revista Iberoamericana de Micología

Revista Iberoamericana de Micología

Volume 31, Issue 3, July–September 2014, Pages 157-175
Revista Iberoamericana de Micología

Special article
EPICO 2.0 project. Development of educational therapeutic recommendations using the DELPHI technique on invasive candidiasis in critically ill adult patients in special situationsProyecto ÉPICO 2.0. Desarrollo de recomendaciones terapéuticas y educativas mediante la metodología DELPHI para pacientes críticos adultos no neutropénicos con candidiasis invasiva en situaciones especiales

https://doi.org/10.1016/j.riam.2014.06.001Get rights and content

Abstract

Background

Although there has been an improved management of invasive candidiasis in the last decade, still controversial issues remain, especially in different therapeutic critical care scenarios.

Aims

We sought to identify the core clinical knowledge and to achieve high agreement recommendations required to care for critically ill adult patients with invasive candidiasis for antifungal treatment in special situations and different scenarios.

Methods

Second prospective Spanish survey reaching consensus by the DELPHI technique, conducted anonymously by electronic e-mail in the first phase to 23 national multidisciplinary experts in invasive fungal infections from five national scientific societies including intensivists, anesthesiologists, microbiologists, pharmacologists and infectious disease specialists, answering 30 questions prepared by a coordination group after a strict review of literature in the last five years. The educational objectives spanned four categories, including peritoneal candidiasis, immunocompromised patients, special situations, and organ failures. The agreement among panelists in each item should be higher than 75% to be selected. In a second phase, after extracting recommendations from the selected items, a meeting was held with more than 60 specialists in a second round invited to validate the preselected recommendations.

Measurements and main results

In the first phase, 15 recommendations were preselected (peritoneal candidiasis (3), immunocompromised patients (6), special situations (3), and organ failures (3)). After the second round the following 13 were validated: Peritoneal candidiasis (3): Source control and early adequate antifungal treatment is mandatory; empirical antifungal treatment is recommended in secondary nosocomial peritonitis with Candida spp. colonization risk factors and in tertiary peritonitis. Immunocompromised patients (5): consider hepatotoxicity and interactions before starting antifungal treatment with azoles in transplanted patients; treat candidemia in neutropenic adult patients with antifungal drugs at least 14 days after the first blood culture negative and until normalization of neutrophils is achieved. Caspofungin, if needed, is the echinocandin with most scientific evidence to treat candidemia in neutropenic adult patients; caspofungin is also the first choice drug to treat febrile candidemia; in neutropenic patients with candidemia remove catheter. Special situations (2): in moderate hepatocellular failure, patients with invasive candidiasis use echinocandins (preferably low doses of anidulafungin and caspofungin) and try to avoid azoles; in case of possible interactions review all the drugs involved and preferably use anidulafungin. Organ failures (3): echinocandins are the safest antifungal drugs; reconsider the use of azoles in patients under renal replacement therapy; all of the echinocandins to treat patients under continuous renal replacement therapy are accepted and do not require dosage adjustment.

Conclusions

Treatment of invasive candidiasis in ICU patients requires a broad range of knowledge and skills as summarized in our recommendations. These recommendations may help to optimize the therapeutic management of these patients in special situations and different scenarios and improve their outcome based on the DELPHI methodology.

Resumen

Antecedentes

Aunque en la última década se ha observado una mejora en el manejo de la candidiasis invasiva, aún es un tema de debate, especialmente aplicado a cuidados intensivos.

Objetivos

Identificar conocimientos clínicos y elaborar recomendaciones con un elevado grado de consenso para orientar la elección de un tratamiento antimicótico adecuado en pacientes adultos críticos no neutropénicos con candidiasis invasiva en condiciones especiales y diversas situaciones.

Métodos

Se realizó el segundo cuestionario prospectivo español con consenso alcanzado mediante la técnica DELPHI. En una primera fase, el cuestionario se envió por correo electrónico a 23 expertos multidisciplinarios nacionales, especialistas en infecciones micóticas invasivas y miembros de cinco sociedades científicas nacionales. Entre los expertos había médicos de cuidados intensivos, anestesistas, microbiólogos, farmacólogos y especialistas en enfermedades infecciosas que respondieron de forma anónima a 30 preguntas preparadas por el grupo de coordinación tras revisar de forma detallada la bibliografía pertinente de los últimos cinco años. Los objetivos educativos contemplaron cuatro categorías: candidiasis peritoneal, pacientes inmunodeprimidos, situaciones especiales e insuficiencia orgánica. El grado de acuerdo alcanzado entre los expertos en cada una de las categorías debía superar el 75% para ser seleccionada. En una segunda fase, tras extraer las recomendaciones de los elementos seleccionados, se celebró una reunión presencial con más de 60 especialistas a quienes se les solicitó la validación de las recomendaciones preseleccionadas.

Mediciones y resultados principales

En la primera fase se realizó una pre selección de 15 recomendaciones (candidiasis peritoneal [3], pacientes inmunodeprimidos [6], situaciones especiales [3], insuficiencia orgánica [3]). Tras la segunda fase, se validaron 13 recomendaciones: candidiasis peritoneal (3): debido al mal pronóstico de la peritonitis candidiásica, se recomienda un adecuado control del foco infeccioso y un tratamiento antimicótico precoz y apropiado. Se recomienda iniciar un tratamiento antimicótico empírico en pacientes con peritonitis secundaria nosocomial y con factores de riesgo de colonización por Candida spp., y en aquellos pacientes con peritonitis terciaria. En la peritonitis candidiásica se recomienda utilizar una equinocandina en los pacientes inestables y en aquellos que han recibido previamente azoles o en los que se aísla Candida resistente a fluconazol. Pacientes inmunodeprimidos (5): en el tratamiento de la candidiasis invasiva con azoles en un paciente con trasplante de órgano sólido se deben tener en cuenta las interacciones y la hepatotoxicidad. En el paciente neutropénico, la duración del tratamiento de la candidemia debe ser de 14 días desde el primer cultivo negativo y hasta la normalización de las cifras de neutrófilos. En un paciente neutropénico con candidemia, caspofungina es la equinocandina que cuenta con más respaldo científico. Caspofungina es también la equinocandina de elección en la neutropenia febril con sospecha de candidemia. En un paciente neutropénico inestable con candidemia y catéter venoso central de fácil recambio es aconsejable la retirada del mismo. Situaciones especiales (2): para el tratamiento de candidiasis invasiva en pacientes con insuficiencia hepática moderada (Child B) se recomienda utilizar equinocandinas (preferentemente anidulafungina o caspofungina en dosis bajas) y se debe evitar el uso de azoles. Aunque las equinocandinas presentan pocas interacciones farmacológicas, se recomienda revisar la medicación concomitante y en el caso de posible interacción, utilizar preferentemente anidulafungina. Insuficiencia orgánica (3): en cuanto a seguridad se refiere, las equinocandinas son la familia de antimicóticos de primera elección. Todas las equinocandinas son iguales para el tratamiento de pacientes sometidos a técnicas continuas de depuración extrarrenal y no precisan ajuste de dosis. El uso de azoles requiere importantes ajustes de dosis en el paciente sometido a técnicas continuas o intermitentes de depuración extrarrenal.

Conclusiones

El manejo de la candidiasis invasiva en pacientes ingresados en la UCI requiere de una serie de conocimientos y pautas que se detallan en nuestras recomendaciones. Estas recomendaciones ayudan a mejorar el tratamiento en distintas situaciones clínicas, lo que puede conducir a mejores desenlaces clínicos mediante el uso de la metodología DELPHI.

Section snippets

Methods

The 23 panel of specialists with a wide geographical distribution in our country, pertaining to the five scientific societies collaborating in the research. The criteria of inclusion were based on their experience in the research of candidemia and on the prognostic and clinical management of critically ill adult patients with confirmed invasive candidiasis.

The DELPHI technique was used to perform the study with the objective of optimizing the consultation process of the 23 panel members. In

First phase. DELPHI experts


‘Peritoneal candidiasis’ section
1.-Indicate your level of agreement with the following statement: In critically ill surgical patients, Candida peritonitis is a poor prognostic factor.

Rationale: The mortality rate associated with Candida peritonitis is very high, ranging from 20 to 70%.19, 23, 42

The vast majority of the experts consulted (95.6%) considered Candida peritonitis a poor prognostic factor in surgical patients. Specifically, and based on a scale of 1–5 points, where 5 represents the

Recommendations after the first phase

Once the results of the DELPHI technique applied to the management of critically ill patients with confirmed invasive candidiasis are known, the following 15 recommendations were elaborated (see Table 1), based on all of the questions that achieved a high/medium level of consensus and, thereafter, validated in the meeting held with the hospital experts.

Second phase. Meeting held with hospital experts

Using the same methodology, 60 hospital experts held a meeting in which they voted the recommendations described in Table 1. Only the statements that received a level of consensus greater than 75% were selected. The final recommendations are shown in Table 2.

Proyecto ÉPICO 2.0. Desarrollo de recomendaciones terapéuticas y educativas mediante la metodología DELPHI para pacientes críticos adultos no neutropénicos con candidiasis invasiva en situaciones especiales

El presente estudio de investigación tiene por objetivo principal analizar la situación actual del manejo del paciente crítico en los hospitales de nuestro país y obtener en esta su segunda edición una serie de recomendaciones terapéuticas en situaciones especiales en el paciente crítico y sus diversos escenarios mediante metodología DELPHI Para ello, en primer término, desde el año 2012 se ha conformado un panel de especialistas de cinco sociedades científicas – Asociación española de

Metodología

El panel de expertos ha sido constituido por 23 especialistas con una amplia distribución geográfica en nuestro país y pertenecientes a las cinco sociedades científicas colaboradoras en la investigación. La razón para su inclusión en el panel obedece a su experiencia tanto en la investigación de la candidemia como en el pronóstico y manejo clínico del paciente crítico con confirmación de candidiasis invasiva.

Para llevar a cabo el estudio se ha empleado la metodología DELPHI con objeto de

Primera fase. Expertos DELPHI


Sección Candidiasis peritoneal
1.- Valore su grado de acuerdo con el siguiente enunciado: En los pacientes críticos quirúrgicos la peritonitis candidiásica es un factor de mal pronóstico.

Rationale: La mortalidad de la peritonitis candidiásica es muy elevada, estableciéndose en torno al 20-70%19, 23, 42.

La inmensa mayoría (95,6%) de los expertos consultados considera que la peritonitis candidiásica es un factor de mal pronóstico en los pacientes quirúrgicos. Concretamente, y en una escala de 1 a

Conflict of interests/Conflicto de intereses

This consensus has been sponsored by MSD Laboratories, Spain.

Este consenso ha sido esponsorizado por laboratorios MSD, España.

Acknowledgements/Agradecimientos

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

A Carmen Romero y Ainhoa Torres (Editorial Entheos) por su excelente trabajo y dedicación a este proyecto.

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    All members are listed in Appendix 1.

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