By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
Dr. Deresinski reports no financial relationships relevant to this field of study.
SYNOPSIS: This updated guideline takes into account newer diagnostic methods and therapeutic agents and their use in the treatment of aspergillosis.
SOURCE: Patterson TE, Thompson III GR, 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 doi: 10.1093/cid/ciw326. First published online: June 29, 2016.
Invasive aspergillosis continues to be a lethal infection in many patients with hematologic malignancy as well as in transplant recipients. This update to the 2008 Infectious Diseases Society of America (IDSA) guidelines provides current recommendations for the diagnosis and management of invasive aspergillosis (IA), chronic (and saprophytic) forms of infection, as well as allergic forms of aspergillosis. The following is a partial summary of the recommendations regarding pulmonary IA.
In patients with prolonged neutropenia at risk of IA, prophylaxis with posaconazole (strong recommendation, high-quality evidence), voriconazole (strong, moderate), or micafungin (weak, low) is recommended. Caspofungin is also believed to probably be effective. Prophylaxis with posaconazole in allogeneic hematopoietic (HSCT) recipients with graft-versus-host disease at high risk of IA is recommended. While voriconazole is commonly used, the evidence is of lower quality than that for use of posaconazole.
In lung transplant recipients, prophylaxis with either a systemically administered triazole or inhaled amphotericin B is recommended for the first three to four months after transplantation. The former is weakly recommended based on low-quality evidence over inhaled amphotericin B in a variety of circumstances, such as those colonized with a mold, those with a mold infection of an explanted lung, fungal infection of paranasal sinuses, or single lung recipients. Antifungal prophylaxis after the initial three-to-four-month window should be reinitiated in those with augmentation of their immunosuppressive therapy with thymoglobulin, alemtuzumab, or high-dose corticosteroids.
The firmest diagnoses are based on histological and cultural analysis with use of molecular techniques for species identification when cultural identification is uncertain or not possible. The role of PCR for diagnosis remains uncertain. Measurement of galactomannan in serum and bronchoalveolar lavage (BAL) fluid is recommended for diagnosis in at-risk populations, i.e., those with hematologic malignancy and HSCT cell transplant recipients. Measurement of (1 → 3)-β-D-glucan is also of use in these patient groups. Galactomannan screening is not recommended in solid organ transplant recipients (or in those with chronic granulomatous disease).
Thoracic computerized tomography (CT) should be performed whenever there is suspicion of pulmonary IA; contrast should not be used unless a nodule or mass abuts a large vessel. Chest CT should not be repeated for at least two weeks unless the patient deteriorates, although earlier repeat CT may be considered if a nodule or mass abuts a large vessel.
Bronchoscopy with BAL should be performed when pulmonary IA is suspected if deemed safe. If feasible, percutaneous or transbronchial biopsy should be considered when one or more peripheral nodular lesions are present.
Voriconazole is the treatment of choice for IA. Treatment should be initiated as early as possible, even prior to completion of the diagnostic evaluation in patients in whom the suspicion of this infection is high. Alternative antifungals include liposomal amphotericin B and isavuconazole. Lipid formulations of amphotericin B other than the liposomal product are another alternative, although the evidence for their use is deemed to be of low quality. A weak recommendation based on moderate-quality evidence is given for the use of voriconazole and an echinocandin in combination in selected patients. Echinocandins should not be used for primary therapy unless alternatives are contraindicated. Treatment should be continued for at least six to 12 weeks. For patients who require subsequent immunosuppressive therapy, secondary prophylaxis should be initiated after completion of the treatment course. The serial measurement of GM can be used to monitor the response to therapy.
Therapeutic drug monitoring of voriconazole, as well as other azoles if used (itraconazole, posaconazole and, possibly, isavuconazole), should be performed, as should monitoring of interacting drugs such as cyclosporine, tacrolimus, and sirolimus.
In addition to antifungal therapy, immunosuppressive therapy should be reduced or eliminated, if feasible. Although a weak recommendation based on low-quality evidence, colony stimulating factors in neutropenic patients or, in highly selected patients, administration of granulocyte transfusions may be considered. Recombinant interferon-γ is a recommended prophylactic agent for patients with chronic granulomatous disease. Surgical intervention is recommended for some types of localized infection.