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Treatment of aspergillosis with itraconazole
1Pharmacy Service, Audie L. Murphy Memorial Veterans Hospital, San Antonio, TX 78284.
Objective:
To review the role of itraconazole as oral therapy for the major infections caused by Aspergillus spp.: allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis.
Data Sources:
A MEDLINE search of articles published in the English language between 1986 and 1993 was used to identify relevant citations, including review articles. In addition, a search of the published abstracts of the past two Interscience Conferences on Antimicrobial Agents and Chemotherapy (ICAAC) was performed.
Study Selection:
Clinical trials that evaluated itraconazole therapy in either allergic bronchopulmonary aspergillosis, aspergilloma, or invasive aspergillosis were critically reviewed. Trials were evaluated based upon entry criteria for the diagnosis of each type of aspergillosis, risk factors for the development of aspergillosis (neutropenia, transplant recipient, hematologic malignancy), prior antifungal chemotherapy, and dose and duration of itraconazole therapy.
Data Synthesis:
Overall, the clinical trials of itraconazole therapy for aspergillosis are limited and of variable quality. In the treatment of allergic bronchopulmonary aspergillosis, itraconazole has been reported to prompt a reduction in corticosteroid dosage in selected patients. There have been no controlled trials of itraconazole as treatment for aspergilloma, but data from several open-label trials suggest that this agent may be of clinical benefit in aspergilloma, primarily as an alternative to surgery. The use of itraconazole for invasive aspergillosis has been evaluated in several trials, most often in patients who were intolerant to amphotericin B treatment. Response to oral itraconazole has generally been promising.
Conclusions:
Although itraconazole offers promise for oral therapy against infections caused by Aspergillus spp., it should not presently be regarded as primary therapy for any of these diseases. Amphotericin B, in doses ranging from 1 to 1.5 mg/kg to a total dose of 1.5-4.0 g, should remain the treatment of choice in both aspergilloma and invasive aspergillosis. Itraconazole use should be restricted to patients who experience severe toxicity with amphotericin B therapy. Corticosteroids continue to be first-line therapy for allergic bronchopulmonary aspergillosis, with the use of itraconazole reserved for those patients who would benefit from a reduction in corticosteroid dose.
Insights
Itraconazole shows promise for Aspergillus infections, but amphotericin B remains the primary treatment. Itraconazole is best for patients intolerant to amphotericin B or needing reduced corticosteroid doses.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Aspergillus species cause serious infections, including allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis.
- Oral antifungal agents are sought for managing these conditions, offering potential advantages over intravenous therapies.
Purpose of the Study:
- To review the efficacy of itraconazole as an oral therapy for major Aspergillus-related infections.
- To evaluate itraconazole's role in allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis.
Main Methods:
- A comprehensive literature search was conducted using MEDLINE (1986-1993) and ICAAC abstracts.
- Clinical trials evaluating itraconazole for aspergillosis were critically reviewed.
- Trial evaluations considered diagnostic criteria, patient risk factors, prior treatments, and itraconazole dosage/duration.
Main Results:
- Limited and variable quality clinical trials exist for itraconazole in aspergillosis.
- Itraconazole may reduce corticosteroid needs in allergic bronchopulmonary aspergillosis.
- Open-label trials suggest potential benefit for itraconazole in aspergilloma as a surgical alternative, and promising responses in invasive aspergillosis, particularly for amphotericin B-intolerant patients.
Conclusions:
- Itraconazole shows promise but is not currently the primary therapy for any major Aspergillus infection.
- Amphotericin B remains the treatment of choice for aspergilloma and invasive aspergillosis.
- Itraconazole should be reserved for patients with severe amphotericin B toxicity or those benefiting from reduced corticosteroid use in allergic bronchopulmonary aspergillosis.