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ECIL-6 Guidelines for the Treatment of Invasive Candidiasis, Aspergillosis

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ECIL-6 Guidelines for the Treatment of Invasive Candidiasis, Aspergillosis GUIDELINE ARTICLE ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis Ferrata Storti EUROPEAN HEMATOLOGY Foundation in leukemia and hematopoietic stem cell ASSOCIATION transplant patients Frederic Tissot, 1 Samir Agrawal, 2 Livio Pagano, 3 Georgios Petrikkos, 4 Andreas H. Groll, 5 Anna Skiada, 6 Cornelia Lass-Flörl, 7 Thierry Calandra, 1 Claudio Viscoli 8 and Raoul Herbrecht 9 1Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland; 2Division of Haemato-Oncology, St Bartholomew's Hospital and Blizard Institute, Queen Mary University, London, UK; 3Hematology, Catholic University of Sacred Heart, Roma, Italy; 4School of Medicine, European University Cyprus, Engomi, Cyprus; 5Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children’s Hospital, Münster, Germany; 61st Department of Medicine, University of Athens, Greece; 7Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Austria; 8 University of Genova (DISSAL), Infectious Disease Division, IRCCS San Martino-IST, Haematologica 2017 Genova, Italy and 9Oncology and Hematology, Hôpitaux Universitaires de Strasbourg and Université de Strasbourg, France Volume 102(3):433-444 ABSTRACT he European Conference on Infections in Leukemia (ECIL) pro - vides recommendations for diagnostic strategies and prophylac - Ttic, pre-emptive or targeted therapy strategies for various types of infection in patients with hematologic malignancies or hematopoietic stem cell transplantation recipients. Meetings are held every two years since 2005 and evidence-based recommendations are elaborated after evaluation of the literature and discussion among specialists of nearly all Correspondence: European countries. In this manuscript, the ECIL group presents the [email protected] 2015-update of the recommendations for the targeted treatment of inva - sive candidiasis, aspergillosis and mucormycosis. Current data now allow a very strong recommendation in favor of echinocandins for Received: August 5, 2016. first-line therapy of candidemia irrespective of the underlying predis - Accepted: December 20, 2016 . posing factors. Anidulafungin has been given the same grading as the Pre-published: December 23, 2016 . other echinocandins for hemato-oncological patients. The beneficial role of catheter removal in candidemia is strengthened. Aspergillus guide - lines now recommend the use of either voriconazole or isavuconazole doi:10.3324/haematol.2016.152900 for first-line treatment of invasive aspergillosis, while first-line combina - Check the online version for the most updated tion antifungal therapy is not routinely recommended. As only few new information on this article, online supplements, data were published since the last ECIL guidelines, no major changes and information on authorship & disclosures: were made to mucormycosis recommendations. www.haematologica.org/content/102/3/433 Introduction ©2017 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. The European Conference on Infections in Leukemia (ECIL) is the result of a col - All rights are reserved to the Ferrata Storti Foundation. Use of laboration between the European Organization for Research and Treatment of published material is allowed under the following terms and conditions: Cancer (EORTC), the European Society for Blood and Marrow Transplantation https://creativecommons.org/licenses/by-nc/4.0/legalcode. (EBMT), the European Leukemia Net (ELN), and the International Copies of published material are allowed for personal or inter - Immunocompromised Host Society (ICSH). First recommendations for the treat - nal use. Sharing published material for non-commercial pur - ment of Candida and Aspergillus infections in hematologic patients were published poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, in 2007 after the first conference (ECIL-1) and have then been updated at ECIL-2 sect. 3. Reproducing and sharing published material for com - 1,2 and ECIL-3. First recommendations for the diagnosis and treatment of mucormy - mercial purposes is not allowed without permission in writing cosis have been published after ECIL-3. 3 ECIL-4 updates for antifungal therapy were from the publisher. only available as slides on the websites of these participating societies without pub - lication of a manuscript in consideration of the lack of substantial new data and the haematologica | 2017; 102(3) 433 F. Tissot et al. limited modifications compared to the latest publication. sive candidiasis, aspergillosis and mucormycosis in leukemia and With respect to the targeted treatment of fungal infec - hematopoietic stem cell transplant patients”. tions, the goals for ECIL-5 were to update the recommen - dations with analysis of the new data for invasive candidi - Invasive candidiasis asis, aspergillosis and mucormycosis in hematologic Like previous ECIL recommendations, the current patients. The update was also necessary to change the guidelines for invasive candidiasis cover the hematologic prior 5-level grading (A to E) used during the ECILs 1 to 4 population as well as the general population of patients. for the strength of recommendations for Candida and Although hematologic patients are the main focus of the Aspergillus infections into the 3-level grading (A to C) recommendation, this distinction is maintained because already used during ECIL-3 for the first recommendation available data from the original randomized controlled tri - for mucormycosis (Table 1). 1-3 The grading for quality of als mainly include non-neutropenic patients. Chronic evidence has not been modified. infections are not considered. Twenty-two major publica - tions were identified (Tables 2 and 3). 5-26 Fifteen reported primary results from clinical trials. 5-11,13-17,19,20 One publica - Methods tion analyzed results of a subgroup of cancer patients from a previously published trial. 12 One publication reported the The ECIL-5 meeting was held in September 2013 and involved analysis of pooled data from 2 trials previously published 57 experts from 21 countries, including 3 non-European countries. with a focus on patients with an underlying malignancy. 21 Slides of the conclusions of the ECIL-5 were made available on the All these studies were published before the ECIL-4. Since websites of the EORTC, EBMT, ELN, and ICHS. The ECIL-6 then, 5 studies have been identified, including one patient- meeting was held in September 2015 with the presence of 55 level quantitative review of 7 published trials on invasive experts from 24 countries, including 4 non-European countries (see candidiasis, one pooled patient-level data analysis from 5 list of collaborators at the end of this Review). prospective trials on anidulafungin, one systematic review At both the ECIL-5 and the ECIL-6 meetings, the antifungal of 17 randomized clinical trials focusing on invasive can - therapy working group made a search for new publications didiasis in neutropenic patients, one prospective non-com - regarding treatment of invasive candidiasis, aspergillosis and parative trial evaluating a strategy of early oral switch mucormycosis. The group was divided into three subgroups, each from anidulafungin for invasive candidiasis, and one being responsible for one of each fungal infection type. The litera - observational study comparing the initial use of ture search was performed in Pubmed and Cochrane databases. echinocandin-based versus azole-based regimen for Abstracts presented at major congresses during the previous two C. parapsilosis candidemia. 22-26 These publications were the years were also retrieved and integrated into the ECIL recommen - reasons for the change in guidelines. Characteristics of dation. All recommendations referring to an abstract, however, these studies and main results are shown in Tables 2 and were classified as provisional until the publication of the final 3. manuscript. The number of neutropenic patients included in each of The working group presented its recommendations during the these studies was low and limited the level of evidence of plenary session at the ECIL-5 meeting and then incorporated the the recommendation for this group of patients. The suggestions coming from the assembly. In cases in which full con - review published by Andes et al . showed that, in the uni - sensus was not obtained, the decision was put to the vote, and the variate analysis, neutropenia was one of the factors signif - final decision was based on a majority of votes from the full ECIL- icantly and negatively associated both with clinical out - 5 assembly. The updated recommendations were presented on the come and with survival. 22 In the multivariate analysis, next day during a second plenary session for final approval. however, the effect of neutropenia disappeared, but there Recommendations were graded on the basis of the strength of rec - was a significant association of immunosuppressive ther - ommendations (3-level scale: A, B, or C) and quality of evidence apy (including steroids) with lower survival. Other factors (3-level scale: I, II, or III), as detailed in Table 1. significantly associated with lower survival were the The manuscript of the ECIL-5 was put on hold after a debate APACHE score, infection by C. tropicalis and age, while arose on differences between ECIL and European Society for treatment
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