Diagnosis and Management of Aspergillosis
Epidemiology and Risk Factors
Prophylaxis
Graft vs. Host Disease (GVHD)
Lung Transplant
Non-lung Solid Organ Transplant
- Prospective trials are lacking to address the need for routine anti-Aspergillus prophylaxis other than for lung transplant recipients.
- Individual risk factors have been identified in cardiac (pre-transplant colonization, reoperation, cytomegalovirus [CMV] infection, renal dysfunction, institutional outbreak), liver (fulminant hepatic failure, reoperation, retransplantation or renal failure), and other organs with institutional outbreaks or prolonged or high-dose corticosteroid use. In such patients, the optimal duration of prophylaxis is not known.
Diagnosis
Galactomannan (GM) and (1→3)-β-D-glucan
Radiographic Diagnosis
Bronchoscopy
Treatment
Antifungal Agents for Aspergillosis
Amphotericin B (AmB)
Echinocandins
Triazoles
Combination Therapy
- However, variable test designs and conflicting results of preclinical and in vitro testing have led to uncertainty as to how to interpret the findings.
Susceptibility Testing
- Antifungal susceptibility testing of Aspergillus isolates using a reference method is reserved for patients suspected to have an azole resistant isolate, who are unresponsive to antifungal agents, or for epidemiological purposes.
Recommended Therapy for Invasive Disease
Invasive Pulmonary Aspergillosis (IPA)
Invasive Aspergillosis (IA)
- There is insufficient evidence regarding the value of G-CSF versus GM-CSF in this setting.
- The benefit for IA in other settings such as in the treatment of endocarditis, osteomyelitis or focal central nervous system (CNS) disease appears rational.
- Other indications are less clear and require consideration of the patient’s immune status, co-morbidities, confirmation of a single focus, and the risks of surgery.
These decisions must consider the risk of progressive aspergillosis during periods of subsequent anti-neoplastic treatment versus the risk of death from the underlying malignancy if this treatment is delayed. ( S , L)
Refractory or Progressive Disease
- The general strategies for salvage therapy typically include:
- changing the class of antifungal
- tapering or reversal of underlying immunosuppression when feasible
- surgical resection of necrotic lesions in selected cases.
Biomarkers to Assess Response
Pediatric Aspergillosis
Transplant and Nontransplant Recipients
- Duration of antifungal therapy is at least 3 months or until TBA is completely resolved, whichever is longer.
Extrapulmonary Aspergillosis
CNS
Endophthalmitis
Keratitis
Paranasal Sinuses
- Enlargement of the sinus ostomy may be needed to improve drainage and prevent recurrence.
Endocarditis, Pericarditis, and Myocarditis
Osteomyelitis and Septic Arthritis
Cutaneous
Peritonitis
Esophageal, Gastrointestinal, and Hepatic
- For extrahepatic or perihepatic biliary obstruction, or localized lesions that are refractory to medical therapy, surgical intervention should be considered.
Renal
- Obstruction of one or both ureters should be managed with decompression if possible and local instillation of AmB deoxycholate.
- Parenchymal disease is best treated with voriconazole.
Ear Infections
Bronchitis in the Non-transplant Population
Breakthrough Infection
- As principles, the IDSA recommends an aggressive and prompt attempt to establish a specific diagnosis with bronchoscopy and/or CT-guided biopsy for peripheral lung lesions.
- Documentation of serum azole levels should be verified if TDM is available for patients receiving mold-active triazoles.
- Antifungal therapy should be empirically changed to an alternative class of antifungal with Aspergillus activity.
- Other considerations include reduction of underlying immunosuppression, if feasible, and susceptibility testing of any Aspergillus isolates recovered from the patient.
Empirical and Pre-emptive Strategies
- The pre-emptive approach can result in more documented cases of IA without compromise in survival and can be used as an alternative to empirical antifungal therapy.
Chronic and Saprophytic Syndromes
- 3 months of chronic pulmonary symptoms or chronic illness or progressive radiographic abnormalities, with cavitation, pleural thickening, peri-cavitary infiltrates and sometimes a fungal ball
- Aspergillus IgG antibody elevated or other microbiological data (The Aspergillus IgG antibody test is the most sensitive microbiological test.)
- No or minimal immunocompromise, usually with one or more underlying pulmonary disorders.
Chronic Cavitary Pulmonary Aspergillosis (CCPA)
- 3 months of chronic pulmonary symptoms or chronic illness or progressive radiographic abnormalities, with cavitation, pleural thickening, peri-cavitary infiltrates and sometimes a fungal ball
- Aspergillus IgG antibody elevated or other microbiological data (The Aspergillus IgG antibody test is the most sensitive microbiological test.)
- No or minimal immunocompromise, usually with one or more underlying pulmonary disorders.
In those who fail therapy, who develop triazole resistance and/or have adverse events,
- Treatment may need to be prolonged.
- The outcomes from surgery are less favorable than those with single aspergilloma, and a careful risk assessment prior to surgical intervention is required.
Aspergilloma
Allergic Syndromes
Allergic Bronchopulmonary Aspergillosis
Allergic Aspergillus Rhinosinusitis
Recommendation Grading
Overview
Title
Diagnosis and Management of Aspergillosis
Authoring Organization
Infectious Diseases Society of America
Endorsing Organization
Pediatric Infectious Diseases Society
Publication Month/Year
July 25, 2016
Last Updated Month/Year
November 25, 2024
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
Aspergillus species continue to be an important cause of life-threatening infection in immunocompromised patients. This at-risk population is comprised of patients with prolonged neutropenia, allogeneic hematopoietic stem cell transplant (HSCT), solid organ transplant (SOT), inherited or acquired immunodeficiencies, corticosteroid use, and others. This document constitutes the guidelines of the Infectious Diseases Society of America (IDSA) for treatment of aspergillosis and replaces the practice guidelines for Aspergillus published in 2008. Since that publication, clinical studies evaluating new and existing therapies including combination therapy for the management of Aspergillus infection have been conducted and the data on use of non-culture-based biomarkers for diagnosing infection have been expanded. The objective of these guidelines is to summarize the current evidence for treatment of different forms of aspergillosis. This document reviews guidelines for management of the 3 major forms of aspergillosis: invasive aspergillosis (IA); chronic (and saprophytic) forms of aspergillosis; and allergic forms of aspergillosis. Given the clinical importance of IA, emphasis is placed upon the diagnosis, treatment, and prevention of the different forms of IA, including invasive pulmonary aspergillosis (IPA), Aspergillus sinusitis, disseminated aspergillosis, and several types of single-organ IA.
Target Patient Population
Patients with Aspergillosis
PICO Questions
How Can the Most Susceptible Patients Be Protected From Aspergillosis, and Which Patients Are Most Susceptible?
How Can a Diagnosis of Invasive Aspergillosis Be Established?
What Antifungal Agents Are Available for the Treatment and Prophylaxis of Invasive Aspergillosis, Including Pharmacologic Considerations, and What Is the Role for Susceptibility Testing?
What Are the Recommended Treatment Regimens and Adjunctive Treatment Measures for the Various Clinical Presentation of Invasive Aspergillosis?
What Are the Recommended Prophylactic Regimens, Who Should Receive Them, and How Should Breakthrough Infection Be Managed?
When Should Patients Be Treated Empirically?
How Should Chronic Aspergillosis, Allergic Syndromes, or Noninvasive Syndromes Be Managed?
Inclusion Criteria
Male, Female, Adolescent, Adult, Child, Older adult
Health Care Settings
Ambulatory, Hospital, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Diagnosis, Assessment and screening, Treatment, Management, Prevention
Diseases/Conditions (MeSH)
D001228 - Aspergillosis, D055732 - Pulmonary Aspergillosis, D001230 - Aspergillus, D055744 - Invasive Pulmonary Aspergillosis
Keywords
fungal infection, aspergillosis, azoles, invasive aspergillosis, allergic aspergillosis, aspergillus
Source Citation
Patterson TF et al. 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-e60