Core Recommendations for Antifungal Stewardship: A Statement of the Mycoses Study Group Education and Research Consortium.

2020

S175-S198

2020 Aug 05

1537-6613

<p>In recent years, the global public health community has increasingly recognized the importance of antimicrobial stewardship (AMS) in the fight to improve outcomes, decrease costs, and curb increases in antimicrobial resistance around the world. However, the subject of antifungal stewardship (AFS) has received less attention. While the principles of AMS guidelines likely apply to stewarding of antifungal agents, there are additional considerations unique to AFS and the complex field of fungal infections that require specific recommendations. In this article, we review the literature on AMS best practices and discuss AFS through the lens of the global core elements of AMS. We offer recommendations for best practices in AFS based on a synthesis of this evidence by an interdisciplinary expert panel of members of the Mycoses Study Group Education and Research Consortium. We also discuss research directions in this rapidly evolving field. AFS is an emerging and important component of AMS, yet requires special considerations in certain areas such as expertise, education, interventions to optimize utilization, therapeutic drug monitoring, and data analysis and reporting.</p>

10.1093/infdis/jiaa394

J. Infect. Dis.

32756879

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

2019

2019 Dec 05

1537-6591

<p><strong>BACKGROUND: </strong>Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential.</p>

<p><strong>METHODS: </strong>To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved.</p>

<p><strong>RESULTS: </strong>There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses.</p>

<p><strong>CONCLUSIONS: </strong>These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.</p>

10.1093/cid/ciz1008

Clin. Infect. Dis.

31802125

Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium.

2019

2019 Nov 04

1474-4457

<p>Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.</p>

10.1016/S1473-3099(19)30312-3

Lancet Infect Dis

31699664

Role of Molecular Biomarkers in the Diagnosis of Invasive Fungal Diseases in Children.

2017

S32-S44

2017 Sep 01

2048-7207

<p>Invasive fungal diseases are important clinical problems that are often complicated by severe illness and therefore the inability to use invasive measures to definitively diagnose the disease. Tests for a range of fungal biomarkers that do not require an invasive sample-collection procedure have been incorporated into adult clinical practice, but pediatric data and pediatric-specific recommendations for some of these diagnostic tools are lacking. In this review, we summarize the published literature and contemporary strategies for using the biomarkers galactomannan, (1→3)-β-d-glucan, Candida mannan antigen and anti-mannan antibody, and fungal polymerase chain reaction for diagnosing invasive fungal disease in children. Data on biomarker use in neonates and children with cancer, history of hematopoietic stem cell transplant, or primary immunodeficiency are included. Fungal biomarker tests performed on blood, other body fluids, or tissue specimens represent promising adjuncts to the diagnostic armamentarium in populations with a high prevalence of invasive fungal disease, but substantial gaps exist in the correct use and interpretation of these diagnostic tools in pediatric patients.</p>

10.1093/jpids/pix054

J Pediatric Infect Dis Soc

28927202

Diagnostic Imaging and Invasive Fungal Diseases in Children.

2017

S22-S31

2017 Sep 01

2048-7207

<p>Invasive fungal disease (IFD) is a life-threatening condition, especially in immunocompromised children. The role of diagnostic imaging in children at risk for an IFD is multifactorial, including initially detecting it, evaluating for dissemination of infection beyond the primary site of disease, monitoring the response to antifungal therapy, and assessing for potential relapse. The objective of this review was to synthesize the published literature relevant to the use of various imaging modalities for the diagnosis and management of IFD in children.</p>

10.1093/jpids/pix055

J Pediatric Infect Dis Soc

28927203

Central Venous Catheter Retention and Mortality in Children With Candidemia: A Retrospective Cohort Analysis.

2015

2015 Aug 16

2048-7207

<p><strong>BACKGROUND: </strong>Candidemia causes significant morbidity and mortality among children. Removal of a central venous catheter (CVC) is often recommended for adults with candidemia to reduce persistent and metastatic infection. Pediatric-specific data on the impact of CVC retention are limited.</p>

<p><strong>METHODS: </strong>A retrospective cohort study of inpatients &lt;19 years with candidemia at the Children's Hospital of Philadelphia between 2000 and 2012 was performed. The final cohort included patients that had a CVC in place at time of blood culture and retained their CVC at least 1 day beyond the blood culture being positive. A structured data collection instrument was used to retrieve patient data. A discrete time failure model, adjusting for age and the complexity of clinical care before onset of candidemia, was used to assess the association of CVC retention and 30-day all-cause mortality.</p>

<p><strong>RESULTS: </strong>Two hundred eighty-five patients with candidemia and a CVC in place at the time of blood culture were identified. Among these 285 patients, 30 (10%) died within 30 days. Central venous catheter retention was associated with a significant increased risk of death on a given day (odds ratio, 2.50; 95% confidence interval, 1.06-5.91).</p>

<p><strong>CONCLUSIONS: </strong>Retention of a CVC was associated with an increased risk of death after adjusting for age and complexity of care at candidemia onset. Although there is likely persistence of unmeasured confounding, given the strong association between catheter retention and death, our data suggest that early CVC removal should be strongly considered.</p>

10.1093/jpids/piv048

J Pediatric Infect Dis Soc

26407279

Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

2016

e1-e50

2016 Feb 15

1537-6591

<p>It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.</p>

10.1093/cid/civ933

Clin. Infect. Dis.

26679628

Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

2016

409-17

2016 Feb 15

1537-6591

<p>It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.</p>

10.1093/cid/civ1194

Clin. Infect. Dis.

26810419

Results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates.

2012

1252-7

2012 Dec

1532-0987

<p><strong>BACKGROUND: </strong>Candida species are the third most common cause of pediatric health care-associated bloodstream infection in the United States and Europe. To our knowledge, this report from the International Pediatric Fungal Network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis.</p>

<p><strong>METHODS: </strong>From 2007 to 2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis.</p>

<p><strong>RESULTS: </strong>Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet Candida albicans was the most common species in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with Candida parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida glabrata was associated with a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates among the classes.</p>

<p><strong>CONCLUSIONS: </strong>We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.</p>

10.1097/INF.0b013e3182737427

Pediatr. Infect. Dis. J.

22982980

Development of new strategies for early diagnosis of mucormycosis from bench to bedside.

2014

2-7

2014 Dec

1439-0507

<p>Early diagnosis and initiation of amphotericin B (AmB) for treatment of mucormycosis increases survival from approximately 40% to 80%. The central objective of a new study of the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) Zygomycosis Working Group is to improve the clinical and laboratory diagnosis of mucormycosis. The diagnostic tools generated from this study may help to significantly improve survival from mucormycosis worldwide. The study has three major objectives: to conduct a prospective international registration of patients with mucormycosis using a well-established global network of centres; to construct a predictive risk model for patients at risk for mucormycosis; and to establish an international archive of specimens of tissues, fluids, and organisms linked from the patients enrolled into the registry that will be used for development of leading edge molecular, proteomic, metabolic and antigenic systems for mucormycosis.</p>

10.1111/myc.12249

Mycoses

25475924