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      Risk factors and clinical outcomes of breakthrough yeast bloodstream infections in patients with hematological malignancies in the era of newer antifungal agents

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          Abstract

          Although yeast bloodstream infections (BSIs) are increasingly being reported in patients with hematological malignancies undergoing antifungal therapy, clinical information regarding breakthrough infections is scarce. The aim of this study was to determine the risk factors for and clinical outcomes of breakthrough yeast BSIs in patients with hematological malignancies in the era of newer antifungal agents. Between 2011 and 2014, all consecutive patients with hematological malignancies who developed yeast BSIs were included in a case-control study wherein breakthrough infections (cases) and de novo infections (controls) were compared. Of 49 patients with yeast BSIs, 21 (43%) met the criteria for breakthrough infections. The proportions of Candida krusei and Candida tropicalis in the cases and controls were significantly different (32% [7/22] vs. 3% [1/29], P = .015; 5% [1/22] vs. 38% [11/29], P = .007, respectively). Acute leukemia, presence of a central venous catheter and neutropenia in the 3 days prior to BSI were significant risk factors for breakthrough infections. Six-week mortality rates was 33% [7/21] in the cases and 43% [12/28] in the controls ( P = .564). Refractory neutropenia and the Pitt bacteremia score were independent predictors of 6-week mortality. In conclusion, breakthrough infections accounted for a significant proportion of yeast BSIs in patients with hematological malignancies. However, these infections did not increase the risk of death by themselves. Our results suggest that current clinical management of breakthrough yeast BSIs, which includes switching to a different antifungal class and prompt catheter removal is reasonable.

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          Most cited references25

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          ESCMID and ECMM joint clinical guidelines for the diagnosis and management of rare invasive yeast infections.

          The mortality associated with invasive fungal infections remains high with that involving rare yeast pathogens other than Candida being no exception. This is in part due to the severe underlying conditions typically predisposing patients to these healthcare-related infections (most often severe neutropenia in patients with haematological malignancies), and in part due to the often challenging intrinsic susceptibility pattern of the pathogens that potentially leads to delayed appropriate antifungal treatment. A panel of experts of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and the European Confederation of Medical Mycology (ECMM) undertook a data review and compiled guidelines for the diagnostic tests and procedures for detection and management of rare invasive yeast infections. The rare yeast pathogens were defined and limited to the following genera/species: Cryptococcus adeliensis, Cryptococcus albidus, Cryptococcus curvatus, Cryptococcus flavescens, Cryptococcus laurentii and Cryptococcus uniguttulatus (often published under the name Filobasidium uniguttulatum), Malassezia furfur, Malassezia globosa, Malassezia pachydermatis and Malassezia restricta, Pseudozyma spp., Rhodotorula glutinis, Rhodotorula minuta and Rhodotorula mucilaginosa, Sporobolomyces spp., Trichosporon asahii, Trichosporon asteroides, Trichosporon dermatis, Trichosporon inkin, Trichosporon jirovecii, Trichosporon loubieri, Trichosporon mucoides and Trichosporon mycotoxinivorans and ascomycetous ones: Geotrichum candidum, Kodamaea ohmeri, Saccharomyces cerevisiae (incl. S. boulardii) and Saprochaete capitatae (Magnusiomyces (Blastoschizomyces) capitatus formerly named Trichosporon capitatum or Geotrichum (Dipodascus) capitatum) and Saprochaete clavata. Recommendations about the microbiological investigation and detection of invasive infection were made and current knowledge on the most appropriate antifungal and supportive treatment was reviewed. In addition, remarks about antifungal susceptibility testing were made. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.
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            Changing epidemiology of systemic fungal infections.

            Species of Candida and Aspergillus remain the most common causes of invasive fungal infections, but other yeasts and filamentous fungi are emerging as significant pathogens. Opportunistic yeast-like fungi and moulds such as Zygomycetes, Fusarium spp. and Scedosporium spp. are increasingly being recognised in patient groups such as those with leukaemia and in bone marrow transplant recipients. Recognition of these epidemiological changes is critical to patient care. The key elements in selecting an appropriate antifungal agent are the type of patient (solid-organ or stem-cell transplant), severity of immunosuppression, history of prolonged exposure to antifungal drugs, and knowledge of the genera and species of the infecting pathogen and its typical susceptibility pattern.
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              Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria.

              Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.
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                Author and article information

                Journal
                Med Mycol
                Med. Mycol
                mmy
                Medical Mycology
                Oxford University Press
                1369-3786
                1460-2709
                February 2018
                19 May 2017
                19 May 2017
                : 56
                : 2
                : 197-206
                Affiliations
                [1 ]Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
                [2 ]Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
                [3 ]Division of Infectious Diseases, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
                [4 ]Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
                Author notes
                To whom correspondence should be addressed. Dong-Gun Lee, MD, PhD, Division of Infectious Diseases, Department of Internal Medicine, The Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. Tel: +82-2-2258-6003; Fax: +82-2-535-2494; E-mail: symonlee@ 123456catholic.ac.kr
                Article
                myx038
                10.1093/mmy/myx038
                5896439
                28525644
                100ad762-d091-4722-a6f7-970b9a827623
                © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 11 December 2016
                : 27 January 2017
                : 17 April 2017
                Page count
                Pages: 10
                Categories
                Original Article

                Infectious disease & Microbiology
                breakthrough infection,yeast,bloodstream infection,hematological malignancy

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