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NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis
D W Denning1, J Y Lee, J S Hostetler
1Department of Medicine, Santa Clara Valley Medical Center, San Jose, California 95128.
Background:
Invasive aspergillosis is the most common invasive mould infection and a major cause of mortality in immunocompromised patients. Response to amphotericin B, the only antifungal agent licensed in the United States for the treatment of aspergillosis, is suboptimal.
Methods:
A multicenter open study with strict entry criteria for invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days followed by 400 mg/d) in patients with various underlying conditions. Response was based on clinical and radiologic criteria plus microbiology, histopathology, and autopsy data. Responses were categorized as complete, partial, or stable. Failure was categorized as an itraconazole failure or overall failure.
Results:
Our study population consisted of 76 evaluable patients. Therapy duration varied from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%) patients had a complete or partial response, and 3 (4%) had a stable response, and in 20 patients (26%), the protocol therapy was discontinued early (at 0.6 to 54.3 weeks) because of a worsening clinical course or death due to aspergillosis (itraconazole failure). Twenty-three (30%) patients withdrew for other reasons including possible toxicity (7%) and death due to another cause but without resolution of aspergillosis (20%). Itraconazole failure rates varied widely according to site of disease and underlying disease group: 14% for pulmonary and tracheobronchial disease, 50% for sinus disease, 63% for central nervous system disease, and 44% for other sites; 7% in solid organ transplant, 29% in allogeneic bone marrow transplant patients, and 14% in those with prolonged granulocytopenia (median 19 days), 44% in AIDS patients, and 32% in other host groups. The relapse rates among those who completed therapy and those who discontinued early for possible toxicity were 12% and 40%, respectively; all were still immunosuppressed.
Conclusion:
Oral itraconazole is a useful alternative therapy for invasive aspergillosis with response rates apparently comparable to amphotericin B. Relapse in immunocompromised patients may be a problem. Controlled trials are necessary to fully assess the role of itraconazole in the treatment of invasive aspergillosis.
Insights
Oral itraconazole shows promise for treating invasive aspergillosis, a serious fungal infection in immunocompromised patients. While response rates appear comparable to amphotericin B, relapse is a concern requiring further study.
Area of Science:
- Mycology
- Infectious Diseases
- Clinical Pharmacology
Background:
- Invasive aspergillosis is a leading cause of mortality in immunocompromised individuals.
- Current treatments, like amphotericin B, have suboptimal response rates.
Purpose of the Study:
- To evaluate the efficacy and safety of oral itraconazole for treating invasive aspergillosis.
- To compare itraconazole's response rates with existing therapies.
Main Methods:
- A multicenter open study involving 76 patients with invasive aspergillosis.
- Patients received oral itraconazole (600 mg/d for 4 days, then 400 mg/d).
- Response was assessed using clinical, radiological, microbiological, and autopsy data.
Main Results:
- 39% of patients achieved a complete or partial response to itraconazole.
- Itraconazole failure rates varied significantly by disease site and patient group (e.g., 14% for pulmonary, 63% for CNS).
- Relapse rates were 12% in patients completing therapy and 40% in those discontinuing early due to toxicity.
Conclusions:
- Oral itraconazole is a viable alternative for invasive aspergillosis treatment.
- Relapse is a significant concern in immunocompromised patients treated with itraconazole.
- Controlled trials are needed to definitively establish itraconazole's role in invasive aspergillosis management.