Physician's Weekly Article - Treating Aspergillosis: Key Recommendations From Updated Guidelines

       New guidelines from the IDSA emphasize that practitioners should use antifungal therapy early to treat and prevent life-threatening aspergillosis infections in immunocompromised patients.

      In 2008, the Infectious Diseases Society of America (IDSA) released new guidelines for the treatment of aspergillosis, replacing guidelines that were previously published in 2000. Aspergillus is one of the most common molds and can be deadly for immunocompromised patients, including individuals undergoing chemotherapy or stem cell transplantation. “Aspergillus is ubiquitous in the environment,” explains John R. Perfect, MD, “but a healthy immune system can prevent these spores from establishing an invasive disease. Patients with an immune system weakened by prolonged neutropenia, on the other hand, are at increased risk for developing aspergillosis, a major fungal complication that can be more difficult to treat.”

      Highlighting Major Changes

The new IDSA guidelines, published in the February 2008 issue of Clinical Infectious Diseases, focus on three major forms of the disease: invasive aspergillosis, chronic types, and allergic aspergillosis. An important revision from previous guidelines is the recommendation of intravenous or oral voriconazole for the primary treatment of invasive pulmonary aspergillosis for most patients (Table). “Since publication of the 2000 IDSA guidelines, voriconazole has demonstrated superiority to deoxycholate amphotericin B, the former gold standard,” says Dr. Perfect. “Furthermore, results from a large randomized, control trial demonstrated that the toxicity of deoxycholate amphotericin B appears to be unsafe, particularly when used in the high doses that are necessary to treat patients with invasive aspergillosis.”

      In patients whose aspergillosis is refractory to voriconazole, recommendations include lipid formulations of amphotericin B, caspofungin, and the triazoles itraconazole and posaconazole (among other agents). “Combination therapy continues to be a topic of discussion when treating aspergillosis,” Dr. Perfect says. “The use of an azole compound and an echinocandin or a polyene and an echinocandin is still being investigated, but there is little evidence suggesting that two drugs are necessarily better than one.” According to the guidelines, the efficacy of combination therapy in the treatment of invasive aspergillosis as primary or salvage therapy remains uncertain and requires future research.

      Prophylaxis of High-Risk Patients

      Antifungal prophylaxis is an important focus of the new ISDA guidelines. Prophylaxis with posaconazole is highly recommended for hematopoietic stem cell transplantation patients with graft-versus-host disease who are at high risk for invasive aspergillosis. The agent is also recommended for neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome. “A recent clinical trial of posaconazole suggests that it’s superior to fluconazole and itraconazole in the prevention of invasive aspergillosis, particularly in patients with acute myeloid leukemia and myelodysplasia,” says Dr. Perfect. “When considering prophylaxis, physicians must identify the risk-benefit ratio for their high-risk patients. The goal should be to avoid exposing patients to unnecessary toxicity. If rates of mortality and morbidity are significant in specific high-risk populations, preventive measures should be taken. An ounce of prevention is potentially worth a pound of cure.”

      The Role of Early Detection

      According to Dr. Perfect, the early detection of aspergillosis infection in high-risk patients is critical. “Aspergillosis is often difficult to diagnose because obtaining cultures in high-risk patients may result in complications, such as bleeding,” he says. “However, delayed diagnoses have a significant impact on the efficacy of disease therapy. In order to treat the underlying disease aggressively, physicians must negate the infection as much as possible to avoid interrupting treatment of the underlying disease, such as chemotherapy. Following patients very carefully with biomarkers and CT scans can help diagnose and treat the infection early.”

      The availability of the galactomannan enzyme immunoassay may also contribute substantially toward a non–culture-based diagnosis of aspergillosis, as well as potentially facilitate therapeutic monitoring. “Galactomannan is a component of the cell wall of Aspergillus that is released in the blood during growth. Using an immunoassay for this component may be useful as an adjunctive test to establish early diagnosis. Unfortunately, the presence of aspergillosis often indicates that the underlying condition is not good because the patient is severely immunosuppressed. Nevertheless, you cannot allow that fungal infection to interrupt the aggressive, consistent delivery of therapy that’s required to treat underlying diseases.”

      Improving Prophylactic Strategies

      Clinicians continue to work on better strategies to manage and prevent aspergillosis. “For example,” Dr. Perfect says, “there is hope that inhaling aerosolized amphotericin B lipid complex into the lungs may prevent the establishment of infection when patients breathe in Aspergillus spores. The hope is that we’ll develop prophylactic strategies that don’t require the systemic administration of a drug and subsequent drug interactions.”

      Dr. Perfect has indicated to Physician’s Weekly that he has or has had the following financial interest: Astellas Pharmas, Enzon, Pfizer, Schering-Plough, and Merck.