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CME

Invasive Aspergillosis

General Information

Description

  • opportunistic, invasive infection with Aspergillus species mold that usually affects patients with immunocompromise2,3,4
  • infection most commonly involves the respiratory tract, presenting as pneumonia, tracheobronchitis, or sinusitis, but may be disseminated2

Definitions

2008 criteria from European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG)

  • 2008 criteria for proven, probable, and possible invasive fungal disease
    • diagnosis of proven invasive fungal disease requires ≥ 1 of
      • histopathologic or cytopathologic exam showing hyphae from needle aspiration or biopsy specimen with evidence of associated tissue damage
      • positive culture result for sample obtained by sterile procedure from normally sterile, and clinically or radiologically abnormal, site consistent with infection
    • diagnosis of probable invasive aspergillosis requires all of
      • ≥ 1 of following host factor criteria
        • recent history of neutropenia (< 500 neutrophils/mm3 for > 10 days) relative to onset of disease
        • allogenic stem cell transplant recipient
        • prolonged corticosteroid use in patients without allergic bronchopulmonary aspergillosis (mean minimum dose 0.3 mg/kg/day prednisone or prednisone equivalent for minimum of 3 weeks)
        • treatment with T cell immunosuppressants, such as cyclosporine, TNF-alpha inhibitors, particular monoclonal antibodies (such as alemtuzumab), or nucleoside analogs within the past 90 days
        • inherited severe immunodeficiency, such as chronic granulomatous disease or severe combined immunodeficiency
      • 1 of following microbiologic criteria
        • positive culture, cytology, or direct microscopy of mold in sputum, bronchoalveolar lavage fluid, bronchial brush sample, or sinus aspirate
        • positive result for Aspergillus galactomannan antigen in plasma, serum, bronchoalveolar lavage fluid, or cerebrospinal fluid
      • 1 of following clinical criteria, temporally consistent with infection
        • ≥ 1 sign on computed tomography (CT) indicating lower respiratory tract fungal disease, including
          • dense, well-circumscribed lesions with or without halo sign
          • air-crescent sign
          • cavity
        • bronchoscopy showing tracheobronchial ulceration, nodule, pseudomembrane, plaque, or eschar
        • sinonasal infection indicated by imaging plus ≥ 1 of
          • acute localized pain
          • extension from paranasal sinus across bony barriers, such as into the orbit
        • central nervous system infection indicated by either
          • focal lesions on imaging
          • meningeal enhancement on magnetic resonance or CT imaging
    • diagnosis of possible invasive aspergillosis requires all of
      • ≥ 1 host factor criterion
      • typical radiological signs in the absence of microbiological support
    • Reference - 18462102Clin Infect Dis 2008 Jun 15;46(12):1813full-text

References

General references used

  1. Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60full-text, commentary can be found in J Thorac Dis 2016 Dec;8(12):E1767
  2. Darling BA, Milder EA. Invasive Aspergillosis. Pediatr Rev. 2018 Sep;39(9):476-478
  3. Cadena J, Thompson GR 3rd, Patterson TF. Invasive Aspergillosis: Current Strategies for Diagnosis and Management. Infect Dis Clin North Am. 2016 Mar;30(1):125-42
  4. Segal BH. Aspergillosis. N Engl J Med. 2009 Apr 30;360(18):1870-84

Recommendation grading systems used

  • Infectious Disease Society of America (IDSA) 2016 recommendation grading system
    • strength of recommendation
      • Strong recommendation - most people should receive recommended course of action
      • Weak recommendation - be prepared to help people make a decision that is consistent with their own values/decision aids and shared decision making
    • quality of evidence
      • High - further research is very unlikely to change confidence in the estimate of effect
      • Moderate - further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate
      • Low - further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate
      • Very low - any estimate of effect is very uncertain
    • Reference - IDSA 2016 practice guideline on diagnosis and management of aspergillosis ( 27365388Clin Infect Dis 2016 Aug 15;63(4):e1)
  • European Society for Clinical Microbiology and Infectious Diseases/European Confederation of Medical Mycology/European Respiratory Society (ESCMID/ECMM/ERS) guideline grading system
    • strength of recommendation grades
      • Grade A - societies strongly support recommendation for use
      • Grade B - societies moderately support recommendation for use
      • Grade C - societies marginally support recommendation for use
      • Grade D - societies support a recommendation against use
    • quality of evidence levels
      • I - evidence from ≥ 1 properly designed randomized, controlled trial (oriented on the primary end point of the trial)
      • II - evidence from
        • ≥ 1 well-designed clinical trial (including secondary end points)
        • cohort or case-controlled analytic studies (preferably from > 1 center)
        • multiple time series, or
        • dramatic results from uncontrolled studies
      • III - evidence from opinions of respected authorities, based on clinical experience, descriptive case studies, or reports of expert committees
    • index of evidence
      • r - meta-analysis or systematic review of randomized, controlled trials
      • t - transferred evidence, such as results of different patient cohorts or similar immune-status situation
      • h - comparator group is historical control
      • u - uncontrolled trial
      • a - abstract or poster of study published at international meeting
    • Reference - ESCMID/ECMM/ERS guideline on diagnosis and management of Aspergillus diseases (Clin Microbiol Infect 2018 May;24 Suppl 1:e1full-text)
  • Center for International Blood and Marrow Transplant Research/National Marrow Donor Program/European Blood and Marrow Transplant Group/American Society of Blood and Marrow Transplantation (CIBMTR/NMDP/EBMT) recommendation grading system
    • grades of recommendation
      • Grade A - strong evidence for efficacy and substantial clinical benefit support recommendation for use; should always be offered
      • Grade B - moderate evidence for efficacy, or strong evidence but only limited clinical benefit, to support recommendation for use; should generally be offered
      • Grade C - insufficient evidence of efficacy to support recommendation for or against use, or evidence for efficacy may not outweigh adverse consequences, or cost of chemoprophylaxis or alternative approaches; optional to offer
      • Grade D - moderate evidence for lack of efficacy or adverse outcome supports a recommendation against use; should generally not be offered
      • Grade E - good evidence for lack of efficacy or adverse outcome supports a recommendation against use; should never be offered
    • levels of evidence
      • I - evidence from ≥ 1 well-executed randomized controlled trial
      • II - evidence from ≥ 1 well-designed nonrandomized clinical trial, cohort or case-control studies, multiple time-series studies, or dramatic results from uncontrolled experiments
      • III - evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees
    • Reference - CIBMTR/NMDP/EBMT guideline on preventing infectious complications among hematopoietic cell transplantation recipients (19747629Biol Blood Marrow Transplant 2009 Oct;15(10):1143full-text), correction can be found in Biol Blood Marrow Transplant 2010 Feb;16(2):294
  • American Thoracic Society (ATS) recommendation grading system
    • grades of recommendation
      • Grade A - good evidence to support recommendation for use
      • Grade B - moderate evidence to support recommendation for use
      • Grade C - poor evidence to support recommendation for or against use
      • Grade D - moderate evidence to support recommendation against use
      • Grade E - good evidence to support recommendation against use
    • quality of evidence ratings
      • I - evidence from ≥ 1 properly randomized controlled trial
      • II - evidence from ≥ 1 well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from > 1 center), from multiple patient series studies, or from dramatic results in uncontrolled experiments
      • III - evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees
    • Reference - ATS statement on treatment of fungal infections in adult pulmonary and critical care patients (21193785Am J Respir Crit Care Med 2011 Jan 1;183(1):96)
  • European Conference on Infections in Leukemia (ECIL) grading system for recommendations
    • strength of recommendations
      • Grade A - good evidence to support use
      • Grade B - moderate evidence to support use
      • Grade C - poor evidence to support use
    • quality of evidence
      • I - evidence from ≥ 1 properly randomized controlled trial
      • II - evidence from ≥ 1 well-designed clinical trial without randomization, case-control or cohort analytical studies (from > 1 center), multiple case series, or exceptional results from uncontrolled experiments
      • III - evidence from opinions of respected authorities (based on clinical experience), descriptive studies, or expert committee reports
    • Reference - ECIL recommendations on use of biological markers for diagnosis of invasive fungal diseases in leukemic patients and hematopoietic stem cell transplant (SCT) recipients (mnh21927034paph76349248pa9h76349248pbyh76349248pcxh76349248pmdc21927034pBone Marrow Transplant 2012 Jun;47(6):846)

Synthesized Recommendation Grading System for DynaMed Content

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  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
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    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
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How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T115708, Invasive Aspergillosis; [updated 2019 Jul 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T115708. Registration and login required.

Published by EBSCO Information Services. Copyright © 2020, EBSCO Information Services. All rights reserved. No part of this may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission.

EBSCO Information Services accepts no liability for advice or information given herein or errors/omissions in the text. It is merely intended as a general informational overview of the subject for the healthcare professional.

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