- Aspergillus species continue to be an important cause of lifethreatening infection in immunocompromised patients. This at-risk population is comprised of patients with prolonged neutropenia, allogeneic hematopoietic stem cell transplant (HSCT), solid-organ transplantation (SOT), inherited or acquired immunodeficiencies, corticosteroid use, and others.
- Additionally, chronic and allergic syndromes due to Aspergillus are recognized to affect an even greater number of additional patients.
- New agents and formulations along with recent studies of the use of older agents are now available for treating patients with these infections, and new diagnostic tools have increased the ability to diagnose these infections in a timely manner.
Epidemiology and Risk Factors
- Hospitalized allogeneic HSCT recipients should be placed in a protected environment to reduce mold exposure (S-L).
- These precautions can be reasonably applied to other highly immunocompromised patients at increased risk for invasive aspergillosis (IA), such as patients receiving induction/re-induction regimens for acute leukemia (S-L).
- In hospitals in which a protected environment is not available, the IDSA recommends admission to a private room, no connection to construction sites, and not allowing plants or cut flowers to be brought into the patient’s room (S-L).
- The IDSA recommends reasonable precautions to reduce mold exposure among outpatients at high risk for IA, including avoidance of gardening, spreading mulch (compost) or close exposure to construction or renovation (S-L).
- Leukemia and transplant centers should perform regular surveillance of cases of invasive mold infection. An increase in incidence over baseline or the occurrence of invasive mold infections in patients who are not at high risk for such infections should prompt evaluation for a hospital source (S-L).
- The IDSA recommends prophylaxis with posaconazole (S-H), voriconazole (S-M), and/or micafungin (W-L) during prolonged neutropenia for those who are at high risk for IA (S-H). Prophylaxis with caspofungin is also probably effective (W-L). Prophylaxis with itraconazole is effective, but therapy may be limited by absorption and tolerability (S-M). Triazoles should not be co-administered with other agents known to have potentially toxic levels with concurrent triazole co-administration (such as vinca alkaloids, and others) (S-M).
Graft vs. Host Disease (GVHD)
- The IDSA recommends prophylaxis with posaconazole for allogeneic HSCT recipients with GVHD who are at high risk for IA (S-H). Prophylaxis with other mold-active azoles is also effective. Voriconazole is commonly used for prophylaxis against IA in high risk patients but did not show improved survival in clinical trials (S-M). Prophylaxis with itraconazole is limited by tolerability and absorption (S-H).
- The IDSA recommends continuation of antifungal prophylaxis throughout the duration of immunosuppression in patients with chronic immunosuppression associated with GVHD (corticosteroid equivalent of >1 mg/kg/day of prednisone for >2 weeks and/or the use of other anti-GVHD therapies, such as lymphocyte depleting agents or tumor necrosis factor-α [TNF-α] inhibition, for refractory GVHD) (S-H).
- The IDSA recommends antifungal prophylaxis with either a systemic triazole such as voriconazole or itraconazole or an inhaled amphotericin B (AmB) product for 3–4 months after lung transplant (S-M).
- Systemic voriconazole or itraconazole is suggested over inhaled amphotericin B for lung transplant recipients with mold colonization pre- or post-lung transplantation, mold infections found in explanted lungs, fungal infections in the sinus, and single lung transplant recipients (W-L).
- The IDSA recommends reinitiating antifungal prophylaxis for lung transplant recipients receiving immunosuppression augmentation with either thymoglobulin, alemtuzumab, or high dose corticosteroids (S-M).
Non-lung Solid Organ Transplant
- The IDSA recommends prophylactic strategies in solid organ transplant recipients based on the institutional epidemiology of infection and assessment of individual risk factors (S-L).
- 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.
- Until molecular tools are more widely used in clinical laboratories, the IDSA recommends that tissue and fluid specimens be submitted in adequate quantities for simultaneous histopathologic/cytologic and culture examination. In the case of isolates with atypical growth or concerns for resistance, species identification by molecular methods should be employed. (S-H).
- As research in the area continues, the IDSA recommends that clinicians choosing to use polymerase chain reaction (PCR) assays employ them carefully in the management of individual patients on a case-by-case basis. Clinicians should be aware of the methodologies and performance characteristics of the specific assay used, and interpret results accordingly. When PCR assays are used, results should be considered in conjunction with other diagnostic tests and the clinical context (S-M).
Galactomannan (GM) and (1→3)-β-D-glucan
- Serum and bronchoalveolar lavage (BAL) GM is recommended as an accurate marker for the diagnosis of IA in adult and pediatric patients when used in certain patient subpopulations (hematologic malignancy, HSCT) (S-H).
- GM is NOT recommended for routine blood screening in patients receiving mold-active antifungal therapy or prophylaxis but can be applied to bronchoscopy specimens from those patients (S-H).
- GM is NOT recommended for screening in solid organ transplant recipients or patients with chronic granulomatous disease (CGD)
- Serum assays for (1→3)-β-D-glucan are recommended for diagnosing IA in high risk patients (hematologic malignancy, allogeneic HSCT), but are NOT specific for Aspergillus (S-M).
- The IDSA recommends performing a chest computed tomographic (CT) scan whenever there is a clinical suspicion of invasive pulmonary aspergillosis (IPA) regardless of chest radiograph results (S-H).
- Routine use of contrast during a chest CT scan for a suspicion of IPA is NOT recommended (S-M). Contrast is recommended when a nodule or a mass is close to a large vessel (S-M).
- The IDSA suggests a follow-up chest CT-scan to assess the response of IPA to treatment after a minimum of two weeks of treatment; earlier assessment is indicated if the patient clinically deteriorates (W-L).
- When a nodule is close to a large vessel, more frequent monitoring may be required (W-L).
- The IDSA recommends performing a bronchoscopy with BAL in patients with a suspicion of IPA (S-M).
- Significant comorbidities such as severe hypoxemia, bleeding, and platelet transfusion-refractory thrombocytopenia may preclude BAL.
- The yield of BAL is low for peripheral nodular lesions, so that percutaneous or endobronchial lung biopsy should be considered.
- The IDSA recommends the use of a standardized BAL procedure and sending the BAL sample for routine culture and cytology as well as non-culture-based methods (e.g., GM) (S-M).