Training should be the first step toward an antifungal stewardship program

doi:10.1016/j.eimc.2014.04.016

Enfermedades Infecciosas y Microbiología Clínica

Volume 33, Issue 4, April 2015, Pages 221-227

https://doi.org/10.1016/j.eimc.2014.04.016 Get rights and content

Abstract

The frequency of use of systemic antifungal agents has increased significantly in most tertiary centers. However, antifungal stewardship has received very little attention. The objective of this article was to assess the knowledge of prescribing physicians in our institution as a first step in the development of an antifungal stewardship program. Attending physicians from the departments that prescribe most antifungals were invited to complete a questionnaire based on current guidelines on diagnosis and therapy of invasive candidiasis and invasive aspergillosis (IA).

The survey was completed by 60.8% (200/329) of the physicians who were invited to participate. The physicians belonged to the following departments: medical (60%), pediatric (19%), intensive care (15.5%), and surgical (5.5%). The mean (±SD) score of correct responses was 5.16 ± 1.73. In the case of candidiasis, only 55% of the physicians clearly distinguished between colonization and infection, and 17.5% knew the local rate of fluconazole resistance. Thirty-three percent knew the accepted indications for antifungal prophylaxis, and 23% the indications for empirical therapy. However, most physicians knew which antifungals to choose when starting empirical therapy (73.5%). As for aspergillosis, most physicians (67%) could differentiate between colonization and infection, and 34.5% knew the diagnostic value of galactomannan. The radiological features of IA were well recognized by 64%, but only 31.5% were aware of the first line of treatment for IA, and 36% of the recommended duration of therapy. The usefulness of antifungal levels was known by 67%. This simple, easily completed questionnaire enabled us to identify which areas of our training strategy could be improved.

Resumen

El uso de antifúngicos sistémicos se ha incrementado significativamente en los grandes hospitales. Sin embargo, la experiencia en el desarrollo de programas de optimización del uso de antifúngicos es muy limitada, pues la mayoría de los esfuerzos se han centrado en el control de los antibacterianos. El objetivo de nuestro estudio fue evaluar el conocimiento de los médicos prescriptores en el diagnóstico y tratamiento de las micosis invasivas en nuestra institución como parte de un programa de optimización del uso de antifúngicos. Se invitó a los médicos prescriptores de los distintos departamentos a completar un cuestionario de 20 preguntas cuya puntuación global fue de 0-10 puntos. Las preguntas se elaboraron de acuerdo a las recomendaciones de las guías de práctica clínica actuales para el diagnóstico y tratamiento de la candidiasis invasiva y la aspergilosis invasiva.

La tasa de respuesta fue de un 60,8% (200/329), de los cuales el 60% correspondió a departamentos médicos, 19% pediátricos, 15,5% unidades de críticos y 5,5% quirúrgicos. La puntuación media obtenida (± DS) fue 5,16 ± 1,73. Respecto a los conocimientos evaluados sobre candidiasis invasiva, un 45% de los médicos no fue capaz de distinguir entre colonización e infección, y solo el 17,5% conocía la tasa de resistencia local a fluconazol. Las indicaciones para profilaxis antifúngica y tratamiento empírico solo fueron correctamente identificadas por el 33% y el 23% de los médicos. Sin embargo, la mayoría identificaron correctamente el tratamiento empírico de elección (73,5%). Respecto a la aspergilosis invasiva, el 67% de los médicos diferenció correctamente colonización de infección y el 34,5% identificó la utilidad clínica de la detección del antígeno galactomanano. El diagnóstico radiológico de la aspergilosis invasiva fue correctamente evaluado por el 64% de los médicos, pero solo el 31,5% y el 36% identificaron correctamente el tratamiento de elección y su duración. La utilidad clínica de la monitorización de antifúngicos solo fue identificada correctamente por el 67% de los médicos. Un cuestionario como el propuesto en este trabajo permite identificar, de una forma ágil, las áreas de conocimientos que deben ser objetivo prioritario de una estrategia educativa dirigida a mejorar el uso de antifúngicos.

Introduction

Invasive fungal infections (IFIs) are a major problem in tertiary care hospitals. They affect several types of patient and are cared for by several types of physician. The difficulties in confirming a diagnosis, the excellent tolerance of new drugs, and the impact of early therapy have led to extended use of empirical antifungal agents.

Previous studies, however, have shown that up to 67–74% of antifungal drugs are used inappropriately in tertiary care hospitals.1, 2, 3 A recent multicenter study performed in French intensive care units (ICU) revealed that 7% of all patients admitted on a single day were receiving antifungals, and 65% patients included had no proven IFI.⁴

International societies have recommended implementation of institutional antifungal stewardship programs.⁵ When antifungal costs surpassed €3 million and while our incidence of proven fungal infection remained stable, we decided to initiate an antifungal stewardship program that included training initiatives. We performed a knowledge survey in order to identify areas requiring specific attention.

Section snippets

Setting and participants

Our institution is a 1550-bed tertiary care hospital attending a population of 715,000 inhabitants. It is a referral center for solid organ transplantation, heart surgery, stem cell transplantation, and HIV-AIDS care.

Ours was a prospective study in which we invited 329 physicians to complete a questionnaire. Hospital areas were ordered according to spending on antifungals by the Pharmacy Department. The participating hospital departments were those that accounted for 85% of antifungal

Results

The questionnaire was completed by 200 of the 329 physicians invited to participate (60.8%; 115 staff [57.5%] and 85 residents [42.5%]). The percentage of responders was higher than 50% for all the departments involved, except for general surgery (40.8%), oncology (20.0%), and pneumology (12.5%). The distribution by departments was as follows: medical (including oncology and hematology) (60%), pediatrics (19%), intensive care unit (15.5%), and surgery (5.5%). The mean age of the responding

Discussion

Ours is the first study to evaluate knowledge of current recommendations on diagnosis and treatment of IFI in a tertiary hospital with a very high consumption of systemic antifungal drugs. We demonstrated that even frequent prescribers have a significant need for continuing medical education in this area. The most common mistakes led to overconsumption of antifungal drugs, since many physicians prescribe combinations and high doses of L-AmB, as well as inappropriate treatment for fungal

Conclusions

A simple test enabled us to assess the knowledge of prescribing physicians about important aspects of the diagnosis, prophylaxis, and treatment of IFIs. Our results revealed serious gaps that require a custom training program that could act as the first step in the implementation of an antifungal stewardship program.

Funding

This study was partially financed by PROMULGA Project (Proyecto Multidisciplinar para Optimizar la Gestión del Uso de Antifúngicos). Instituto de Salud Carlos III. PI1002868.

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Evaluation of a stewardship program of antifungal use at a Brazilian tertiary care hospital
2022, Brazilian Journal of Infectious Diseases
Stewardship programs have been developed to optimize the use of antibiotics, but programs focusing on antifungal agents are less frequent.
To evaluate the quality of antifungal prescriptions in a tertiary care hospital, and to test if a simple educational activity could improve the quality of prescriptions.
The study comprised three phases: 1) Retrospective audit of all antifungal prescriptions in a 6-month period, applying a score based on six parameters: indication, drug, dosage, route of administration, microbiologic adequacy after results of cultures, switching to an oral agent, and duration of treatment; 2) Creation of text boxes in the electronic medical records with information about antifungal agents, shown during prescription; 3) Retrospective audit of all antifungal prescriptions in a 6-month period, applying the same 6-parameters score, and comparison between the two periods.
Among 333 prescriptions, fluconazole was the most frequently (80.5%) prescribed agent. Hematology (26.7%), Infectious Diseases Department (22.8%), Internal Medicine (15.9%) and Intensive Care Unit (14.4%) were the units with most antifungal prescriptions. The median score for the 333 prescriptions was 8.0 (range 0 – 10), and 72.7% of prescriptions were considered inappropriate. The median and mean scores in the first and second audit were 8.0 and 6.9, and 8.0 and 7.9, respectively (p<0.001). All items that comprised the score improved from the first to the second audit. Likewise, there was a reduction of inappropriate prescriptions (80.2% in the first audit vs. 64.6% in the second audit, p=0.001).
A large proportion of inappropriate prescriptions was observed, which improved with the implementation of simple educational activities.
The global problem of antifungal resistance: prevalence, mechanisms, and management
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Citation Excerpt :
In many centres, antimicrobial stewardship tools are not readily available because of poor access to diagnostic tests with long turn-around times. Guidelines that only cover the most common fungal infections and patient settings, combined with a generally poor understanding of fungal infections outside of specialist clinical teams, adds to the challenge of successful antimicrobial stewardship.106 Newer drugs with lower toxicities than drugs such as amphotericin B have increased empirical and prophylactic use of antifungals in many patient groups, which affects antifungal resistance and is also financially unsustainable.107
All serious fungal infections need appropriate antifungal therapy for successful patient outcome. Only a few classes of antifungal drugs are available, so the emergence of resistance to single drug classes and now multidrug resistance greatly hampers patient management. Azole resistance among Candida and Aspergillus species is one of the greatest challenges to clinical success, followed by echinocandin and multidrug resistance among some Candida species, especially Candida glabrata. The spread of agriculturally derived azole-resistant Aspergillus fumigatus and emerging threats such as multidrug resistant Candida auris are also alarming. The molecular mechanisms that cause drug resistance are naturally occurring in less susceptible species and are acquired in strains of susceptible organisms. Drug resistance mechanisms include altered drug-target interactions, reduced cellular drug concentrations mediated by drug efflux transporters, and permeability barriers associated with biofilms. Although C auris is inherently multidrug resistant, other strains typically develop resistance through stepwise selection of multiple drug-resistance mechanisms. Cellular stress induced by drug treatment promotes adaptation, which contributes to breakthrough resistance. Drug exposure also drives the emergence of resistance. An effective antifungal stewardship programme is essential to control drug resistance, and should incorporate rapid fungal diagnostics, therapeutic drug monitoring, and clinical intervention teams. The development of better diagnostic tools and strategies that allow targeted use of antifungals is essential to preserve drug effectiveness.
EPICO 4.0. ‘Total quality’ in the management of invasive candidiasis in critically ill patients by analysing the integrated process
2017, Revista Iberoamericana de Micologia
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The coordinators provided the following answers (Block A): Raising awareness of the problem of inadequate use of antimicrobials; Convey the need to form teams to lead the PROAs to improve the quality of care; Improve suitability of empirical antifungal treatment; Optimize dosing regimens based on the pharmacokinetic-pharmacodynamics (PK-PD) indices of antifungal drugs; and Discontinue antifungal treatment in the absence of proven fungal infection. The literature contains many studies in which the roles and responsibilities of the multidisciplinary team for antimicrobial stewardship programs in hospitals are defined.3,25,48,53,56,57 Thus, and as a guide for action, some papers describe stewardship programs for antibiotic treatment similar to PROA on antifungal treatment in invasive candidiasis.51
A high quality integrated process in the clinical setting of non-neutropenic critically ill patients at risk for invasive candidiasis is a necessary tool to improve the management of these patients.
To identify the key points on invasive candidiasis in order to develop a set of recommendations with a high level of consensus required for the creation of a total quality integrated process for the management of non-neutropenic critically ill patients at risk of invasive candidiasis.
After a thorough review of the literature of the previous five years, a Spanish prospective questionnaire, which measured consensus by the Delphi technique, was anonymously conducted by e-mail, including 31 national multidisciplinary experts with extensive experience in invasive fungal infections, from six national scientific societies. The experts included a specialist in intensive care medicine, anesthetists, microbiologists, pharmacologists, and specialists in infectious diseases that responded 27 questions prepared by the coordination group. The educational objectives considered six processes that included knowledge of the local epidemiology, the creation and development of multidisciplinary teams, the definitions of the process, protocols, and indicators (KPI), an educational phase, hospital implementation, and the measurement of outcomes. The level of agreement among experts in each category to be selected should exceed 70%. In a second phase, after drawing up the recommendations of the selected processes, a face to face meeting with more than 60 specialists was held. The specialists were asked to validate the pre-selected recommendations.
Firstly, 20 recommendations from all the sections were pre-selected: Knowledge of local epidemiology (3 recommendations), creation and development of multidisciplinary teams (3), definition of the process, protocols and indicators (1), educational phase (3), hospital implementation (3), and measurement of outcomes (7). After the second phase, 18 recommendations were validated, and it was concluded that the minimum team or core necessary for the development of an efficient program in the use of antifungal drugs in non-neutropenic critically ill patients must consist of a specialist in infectious diseases, a clinical pharmacist, a microbiologist, a specialist in intensive care medicine, a specialist in anesthesia and recovery, and an administrator or member of the medical management team, and, in order to be cost-effective, it should be implemented in hospitals with over 200 beds. In addition, it is recommended to apply a consensual check list for the evaluation of the diagnostic process and treatment of invasive candidiasis in patients that have started an antifungal treatment. The management of external knowledge and individual learning stand out as active educational strategies. The main strategies for measuring patient safety outcomes are the analysis of the results achieved, and learning activities; assess, review and refine the deployment of the processes; quality control; epidemiological surveillance and applied research; benchmarking; and basic research. The results of the integrated process should be annually disseminated outside the hospital.
Optimizing the management of invasive candidiasis requires the application of the knowledge and skills detailed in our recommendations. These recommendations, based on the Delphi methodology, facilitate the creation of a total quality integrated process in critically-ill patients at risk for invasive candidiasis.
El adecuado manejo de los pacientes críticos no neutropénicos en situación de riesgo de contraer una candidiasis invasiva requiere la implementación de protocolos de alta calidad en la actuación clínica.
Identificar los principales conocimientos y elaborar recomendaciones con un alto nivel de consenso, necesarios para la creación de un proceso integrado de calidad total para el manejo del paciente crítico no neutropénico con riesgo de candidiasis invasiva.
Se realizó un cuestionario prospectivo que mide el grado de consenso mediante la técnica Delphi, de forma anónima y por correo electrónico, entre 31 expertos multidisciplinarios, especialistas en infecciones fúngicas invasivas de seis sociedades científicas, que incluyen intensivistas, anestesistas, microbiólogos, farmacólogos y especialistas en enfermedades infecciosas que respondieron a 27 preguntas preparadas por el grupo de coordinación, tras una revisión exhaustiva de la literatura de los últimos cinco años. Los objetivos educativos contemplaron seis procesos, que incluían el conocimiento de la epidemiología local, la creación y el desarrollo de equipos multidisciplinares, la definición de proceso, protocolos e indicadores (KPI), una fase educacional, la implementación hospitalaria y la medición de resultados. El grado de acuerdo alcanzado entre los expertos en cada una de las categorías debía superar el 70% para ser seleccionada. Después de extraer las recomendaciones de los procesos escogidos, se celebró una reunión presencial con más de 60 especialistas y se les solicitó la validación de las recomendaciones preseleccionadas.
En un primer término se realizó una preselección de 20 recomendaciones de los siguientes apartados: Conocimiento de la epidemiología local (3), Creación y desarrollo de equipos multidisciplinares (3), Definición de proceso, protocolos e indicadores (1), Fase educacional (3), Implementación hospitalaria (3), Medición de resultados (7). Después de la segunda ronda se validaron 18 recomendaciones que se resumen en que el equipo mínimo (núcleo) necesario para un programa eficiente en el uso de fármacos antifúngicos para el paciente crítico no neutropénico debe estar integrado por un especialista en enfermedades infecciosas, un farmacéutico, un microbiólogo, un especialista en medicina intensiva, un especialista en anestesia y reanimación y un gestor o miembro de la dirección médica. Debería implementarse en hospitales de más de 200 camas para ser coste-efectivo. Además, se recomienda aplicar una lista de comprobación consensuada para la evaluación del proceso de diagnóstico y tratamiento de la candidiasis invasiva en los pacientes en los que se inicie un tratamiento antifúngico. Se destacan como estrategias de educación activa la gestión del conocimiento externo y del aprendizaje individual. Las principales estrategias para medir los resultados de seguridad del paciente son el análisis de los resultados obtenidos que comprenden la comprobación y revisión del proceso, control de calidad, vigilancia epidemiológica, benchmarking e investigación básica. Los resultados del proceso integrado deberían difundirse anualmente fuera del hospital.
La optimización del manejo de la candidiasis invasiva requiere de la aplicación de los conocimientos y destrezas que se detallan en nuestras recomendaciones. Estas recomendaciones basadas en la metodología Delphi, facilitan la creación de un proceso integrado de manejo con calidad total del paciente crítico con riesgo de candidiasis invasiva.
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This information was used to design interactive training courses based on clinical cases. A 20-point questionnaire was administered to all participants before and after the course to evaluate the impact and effectiveness of the course [11]. We performed an audit of the use and cost of 100 antifungal prescriptions (December 2010 to January 2011) according to a quality score (scale of 0 to 10) for evaluation of the adequacy of the prescription (Table 1).
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Original articleTraining should be the first step toward an antifungal stewardship programLa formación debe ser el primer paso en el desarrollo de un programa de optimización del uso de antifúngicos

Abstract

Resumen

Introduction

Section snippets

Setting and participants

Results

Discussion

Conclusions

Funding

Int J Antimicrob Agents

Diagn Microbiol Infect Dis

Impact of education and an antifungal stewardship program for candidiasis at a Thai tertiary care center

Infect Control Hosp Epidemiol

Inappropriate use of antifungal medications in a tertiary care center in Thailand: a prospective study

Infect Control Hosp Epidemiol

An audit of the use of antifungal agents

J Antimicrob Chemother

Systemic antifungal therapy in critically ill patients without invasive fungal infection

Crit Care Med

Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship

Clin Infect Dis

Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America

Clin Infect Dis

Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America

Clin Infect Dis

Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients

Crit Care Med

Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination

Intensive Care Med

Fluconazole improves survival in septic shock: a randomized double-blind prospective study

Crit Care Med

Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients

Ann Surg

Fluconazole prophylaxis in critically ill surgical patients: a meta-analysis

Crit Care Med

Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials

J Antimicrob Chemother

Antifungals in the ICU

Curr Opin Infect Dis

Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death

J Antimicrob Chemother

Original article
Training should be the first step toward an antifungal stewardship programLa formación debe ser el primer paso en el desarrollo de un programa de optimización del uso de antifúngicos