Defining Opportunistic Invasive Fungal Infections in Immunocompromised Patients with Cancer and Hematopoietic Stem Cell Transplants: An International Consensus
TL;DR: A set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed and three levels of probability are proposed: "proven," "probable," and "possible."
Abstract: During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial controversy concerning optimal diagnostic criteria for these IFIs. Therefore, members of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group formed a consensus committee to develop standard definitions for IFIs for clinical research. On the basis of a review of literature and an international consensus, a set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed. Three levels of probability are proposed: "proven," "probable," and "possible." The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making.
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Radboud University Nijmegen1, National Institutes of Health2, Stanford University3, University of California, Los Angeles4, University of Lausanne5, University of Alabama6, University of Paris7, University of Michigan8, University of Texas Health Science Center at San Antonio9, University of Strasbourg10, University of Manchester11, University College London12, Oregon Health & Science University13, Complutense University of Madrid14, University of Aberdeen15, Duke University16, Charité17, University at Buffalo18, Wayne State University19, University of Sydney20, University of Genoa21, University of Florida22, University of Pennsylvania23
TL;DR: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
Abstract: BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
4,389 citations
Cites background or methods from "Defining Opportunistic Invasive Fun..."
...1086/588660 zation for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) published standard definitions for invasive fungal infections for clinical and epidemiological research [1]....
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...Since the first definitions were published [1], the FDA has approved the Aspergillus galactomannan EIA and, more recently, the assay for b-d-glucan, on the grounds that they were standardized, were validated, are available, and are fit to convey useful information [8, 19, 27]....
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National Institutes of Health1, University of Arkansas for Medical Sciences2, University of Manchester3, University of Strasbourg4, Oregon Health & Science University5, University of Minnesota6, Veterans Health Administration7, Roswell Park Cancer Institute8, Duke University9, Stanford University10, Santa Clara Valley Medical Center11, University of Florida12, University of Texas Health Science Center at San Antonio13
TL;DR: This research presents a novel, scalable, scalable and scalable approach that allows for real-time evaluation of the impact of Epstein-Barr virus on the development and management of childhood cancer in rats.
Abstract: Aspergillus species have emerged as an important cause of life-threatening infections in immunocompromised patients. This expanding population is composed of patients with prolonged neutropenia, advanced HIV infection, and inherited immunodeficiency and patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) and/or lung transplantation. This document constitutes the guidelines of the Infectious Diseases Society of America for treatment of aspergillosis and replaces the practice guidelines for Aspergillus published in 2000 [1]. The objective of these guidelines is to summarize the current evidence for treatment of different forms of aspergillosis. The quality of evidence for treatment is scored according to a standard system used in other Infectious Diseases Society of America guidelines. This document reviews guidelines for management of the 3 major forms of aspergillosis: invasive aspergillosis, chronic (and saprophytic) forms of aspergillosis, and allergic forms of aspergillosis. Given the public health importance of invasive aspergillosis, emphasis is placed on the diagnosis, treatment, and prevention of the different forms of invasive aspergillosis, including invasive pulmonary aspergillosis, sinus aspergillosis, disseminated aspergillosis, and several types of single-organ invasive aspergillosis. There are few randomized trials on the treatment of invasive aspergillosis. The largest randomized controlled trial demonstrates that voriconazole is superior to deoxycholate amphotericin B (D-AMB) as primary treatment for invasive aspergillosis. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients (A-I). Although invasive pulmonary aspergillosis accounts for the preponderance of cases treated with voriconazole, voriconazole has been used in enough cases of extrapulmonary and disseminated infection to allow one to infer that voriconazole is effective in these cases. A randomized trial comparing 2 doses of liposomal amphotericin B (L-AMB) showed similar efficacy in both arms, suggesting that liposomal therapy could be considered as alternative primary therapy in some patients (A-I). For salvage therapy, agents include lipid formulations of amphotericin (LFAB; A-II), posaconazole (B-II), itraconazole (B-II), caspofungin (B-II), or micafungin (B-II). Salvage therapy for invasive aspergillosis poses important challenges with significant gaps in knowledge. In patients whose aspergillosis is refractory to voriconazole, a paucity of data exist to guide management. Therapeutic options include a change of class using an amphotericin B (AMB) formulation or an echinocandin, such as caspofungin (B-II); further use of azoles should take into account host factors and pharmacokinetic considerations. Refractory infection may respond to a change to another drug class (B-II) or to a combination of agents (B-II). The role of combination therapy in the treatment of invasive aspergillosis as primary or salvage therapy is uncertain and warrants a prospective, controlled clinical trial. Assessment of patients with refractory aspergillosis may be difficult. In evaluating such patients, the diagnosis of invasive aspergillosis should be established if it was previously uncertain and should be confirmed if it was previously known. The drug dosage should be considered. Management options include a change to intravenous (IV) therapy, therapeutic monitoring of drug levels, change of drug class, and/or combination therapy. Antifungal prophylaxis with posaconazole can be recommended in the subgroup of HSCT recipients with graft-versus-host disease (GVHD) who are at high risk for invasive aspergillosis and in neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome who are at high risk for invasive aspergillosis (A-I). Management of breakthrough invasive aspergillosis in the context of mould-active azole prophylaxis is not defined by clinical trial data. The approach to such patients should be individualized on the basis of clinical criteria, including host immunosuppression, underlying disease, and site of infection, as well as consideration of antifungal dosing, therapeutic monitoring of drug levels, a switch to IV therapy, and/or a switch to another drug class (B-III). Certain conditions of invasive aspergillosis warrant consideration for surgical resection of the infected focus. These include but are not limited to pulmonary lesions contiguous with the heart or great vessels, invasion of the chest wall, osteomyelitis, pericardial infection, and endocarditis (B-III). Restoration of impaired host defenses is critical for improved outcome of invasive aspergillosis (A-III). Recovery from neutropenia in a persistently neutropenic host or reduction of corticosteroids in a patient receiving high-dose glucocorticosteroids is paramount for improved outcome in invasive aspergillosis. A special consideration is made concerning recommendations for therapy of aspergillosis in uncommon sites, such as osteomyelitis and endocarditis. There are very limited data on these infections, and most involve D-AMB as primary therapy simply because of its long-standing availability. Based on the strength of the randomized study, the panel recommends voriconazole for primary treatment of these very uncommon manifestations of invasive aspergillosis (B-III). Management of the chronic or saprophytic forms of aspergillosis varies depending on the condition. Single pulmonary aspergillomas may be best managed by surgical resection (B-III), whereas chronic cavitary and chronic necrotizing pulmonary aspergillosis require long-term medical therapy (B-III). The management of allergic forms of aspergillosis involves a combination of medical and anti-inflammatory therapy. For example, management of allergic bronchopulmonary aspergillosis (ABPA) involves the administration of itraconazole and corticosteroids (A-I). © 2008 by the Infectious Diseases Society of America. All rights reserved.
2,463 citations
Cites methods from "Defining Opportunistic Invasive Fun..."
...Second, the European Organization for Research in Treatment of Cancer–Mycoses Study Group document clearly articulates that the consensus definitions are not intended to be a direct guide to practice [23]....
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...Members of the European Organization for Research in Treatment of Cancer–Invasive Fungal Infection Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group formed a Consensus Committee to develop standard definitions for invasive fungal infections for clinical research [23]....
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Veterans Health Administration1, University of Miami2, San Francisco General Hospital3, University of California, San Francisco4, University of Missouri5, University of California, Los Angeles6, Tufts University7, University of Washington8, University of Minnesota9, Stanford University10, Palo Alto Medical Foundation11, VA Palo Alto Healthcare System12, Medical College of Wisconsin13
TL;DR: It is the recommendation of this committee that patients with soft-tissue infection be distinguished by signs and symptoms of systemic toxicity (e.g., fever or hypothermia, tachycardia [heart rate,] and so on).
Abstract: EXECUTIVE SUMMARYSoft-tissue infections are common, generally of mild tomodest severity, and are easily treated with a variety ofagents. An etiologic diagnosis of simple cellulitis is fre-quently difficult and generally unnecessary for patientswith mild signs and symptoms of illness. Clinical as-sessment of the severity of infection is crucial, and sev-eral classification schemes and algorithms have beenproposed to guide the clinician [1]. However, mostclinical assessments have been developed from eitherretrospective studies or from an author’s own “clinicalexperience,” illustrating the need for prospectivestudieswith defined measurements of severity coupled to man-agement issues and outcomes.Until then, it is the recommendation of this com-mittee that patients with soft-tissue infection accom-panied by signs and symptoms of systemic toxicity (e.g.,fever or hypothermia, tachycardia [heart rate,
2,008 citations
TL;DR: This guideline addresses the wide array of SSTIs that occur in this population and emphasizes the importance of clinical skills in promptly diagnosing SSTI, identifying the pathogen, and administering effective treatments in a timely fashion.
Abstract: A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.
1,856 citations
TL;DR: In patients undergoing chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome, posaconazoles prevented invasive fungal infections more effectively than did either fluconazole or itraconazole and improved overall survival.
Abstract: Background Patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome are at high risk for difficult-to-treat and often fatal invasive fungal infections. Methods In this randomized, multicenter study involving evaluators who were unaware of treatment assignments, we compared the efficacy and safety of posaconazole with those of fluconazole or itraconazole as prophylaxis for patients with prolonged neutropenia. Patients received prophylaxis with each cycle of chemotherapy until recovery from neutropenia and complete remission, until occurrence of an invasive fungal infection, or for up to 12 weeks, whichever came first. We compared the incidence of proven or probable invasive fungal infections during treatment (the primary end point) between the posaconazole and fluconazole or itraconazole groups; death from any cause and time to death were secondary end points. Results A total of 304 patients were randomly assigned to receive posaconazole, and 298 ...
1,516 citations
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TL;DR: Evidence Based Medicine (IBM) as discussed by the authors is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients, which is a hot topic for clinicians, public health practitioners, purchasers, planners and the public.
Abstract: It's about integrating individual clinical expertise and the best external evidence
Evidence based medicine, whose philosophical origins extend back to mid-19th century Paris and earlier, remains a hot topic for clinicians, public health practitioners, purchasers, planners, and the public. There are now frequent workshops in how to practice and teach it (one sponsored by the BMJ will be held in London on 24 April); undergraduate1 and postgraduate2 training programmes are incorporating it3 (or pondering how to do so); British centres for evidence based practice have been established or planned in adult medicine, child health, surgery, pathology, pharmacotherapy, nursing, general practice, and dentistry; the Cochrane Collaboration and Britain's Centre for Review and Dissemination in York are providing systematic reviews of the effects of health care; new evidence based practice journals are being launched; and it has become a common topic in the lay media. But enthusiasm has been mixed with some negative reaction.4 5 6 Criticism has ranged from evidence based medicine being old hat to it being a dangerous innovation, perpetrated by the arrogant to serve cost cutters and suppress clinical freedom. As evidence based medicine continues to evolve and adapt, now is a useful time to refine the discussion of what it is and what it is not.
Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The …
12,134 citations
Journal Article•
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2,849 citations
TL;DR: The potential benefits, limitations, and harms of clinical guidelines are examined, a tool for making care more consistent and efficient and for closing the gap between what clinicians do and what scientific evidence supports.
Abstract: This is the first in a series of four articles on issues in the development and use of clinical guidelines
Over the past decade, clinical guidelines have increasingly become a familiar part of clinical practice. Every day, clinical decisions at the bedside, rules of operation at hospitals and clinics, and health spending by governments and insurers are being influenced by guidelines. As defined by the Institute of Medicine, clinical guidelines are “systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances.”1 They may offer concise instructions on which diagnostic or screening tests to order, how to provide medical or surgical services, how long patients should stay in hospital, or other details of clinical practice
The broad interest in clinical guidelines that is stretching across Europe, North America, Australia, New Zealand, and Africa (box) has its origin in issues that most healthcare systems face: rising healthcare costs, fueled by increased demand for care, more expensive technologies, and an ageing population; variations in service delivery among providers, hospitals, and geographical regions and the presumption that at least some of this variation stems from inappropriate care, either overuse or underuse of services; and the intrinsic desire of healthcare professionals to offer, and of patients to receive, the best care possible. Clinicians, policy makers, and payers see guidelines as a tool for making care more consistent and efficient and for closing the gap between what clinicians do and what scientific evidence supports.
As guidelines diffuse into medicine, there are important lessons to learn from the firsthand experience of those who develop, evaluate, and use them.3 This article, the first of a four part series to reflect on these lessons, examines the potential benefits, limitations, and harms of clinical guidelines. Future articles will review lessons learned …
2,316 citations
"Defining Opportunistic Invasive Fun..." refers background in this paper
...Strategies to minimize such uncertainties have resulted in movements such as evidence-based medicine [3] and practice guidelines [ 4 ]....
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...False-positive cryptococcal antigen reactions due to infection with Trichosporon beigelii [1], infection with Stomatococcus mucilaginosis [2], circulating rheumatoid factor [3], and concomitant malignancy [ 4 ] may occur and should be eliminated if positive antigen test is only positive result in this category....
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Book•
24 Apr 1986
TL;DR: This chapter discusses the design and execution of case-control and Cohort studies, as well as methods of Sampling and Estimation of Sample Size, and statistical analysis of these studies.
Abstract: 1. Introduction 2. Biologic and Statistical Concepts 3. Sources of Routinely Collected Data on Disease Occurrence 4. Prospective Cohort Studies: Planning and Execution 5. Retrospective Cohort, Nested Case-Control and Case-Cohort Studies: Planning and Execution 6. Cohort Studies: Statistical Analysis I 7. Cohort Studies: Statistical Analysis II 8. Case-Control Studies: Planning and Execution 9. Case-Control Studies: Further Design Consideration and Statistical Analysis 10. Crossd-Sectional and Other Types of Studies 11. Epidemic Investigation 12. Methods of Sampling and Estimation of Sample Size 13. Measurement Error 14. Measurement I: Questionnaires 15. Measurement II: Other Types of Measurement
1,457 citations