NIAID mycoses study group multicenter trial of oral itraconazole therapy for invasive aspergillosis

David W. Denning, Jeanette Y. Lee, John S. Hostetler, Peter Pappas, Carol A. Kauffman, Daniel H. Dewsnup, John N Galgiani, John R. Graybill, Alan M. Sugar, Antonino Catanzaro, Harry Gallis, John R. Perfect, Bonita Dockery, William E. Dismukes, David A. Stevens

Research output: Contribution to journalArticle

433 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalAmerican Journal of Medicine
Volume97
Issue number2
DOIs
StatePublished - 1994

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National Institute of Allergy and Infectious Diseases (U.S.)
Itraconazole
Aspergillosis
Mycoses
Multicenter Studies
Immunocompromised Host
Amphotericin B
Therapeutics
Transplants
Recurrence
Agranulocytosis
Antifungal Agents
Central Nervous System Diseases
Complementary Therapies
Microbiology
Lung Diseases
Autopsy
Acquired Immunodeficiency Syndrome
Fungi
Bone Marrow

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Denning, D. W., Lee, J. Y., Hostetler, J. S., Pappas, P., Kauffman, C. A., Dewsnup, D. H., ... Stevens, D. A. (1994). NIAID mycoses study group multicenter trial of oral itraconazole therapy for invasive aspergillosis. American Journal of Medicine, 97(2), 135-144. https://doi.org/10.1016/0002-9343(94)90023-X

NIAID mycoses study group multicenter trial of oral itraconazole therapy for invasive aspergillosis. / Denning, David W.; Lee, Jeanette Y.; Hostetler, John S.; Pappas, Peter; Kauffman, Carol A.; Dewsnup, Daniel H.; Galgiani, John N; Graybill, John R.; Sugar, Alan M.; Catanzaro, Antonino; Gallis, Harry; Perfect, John R.; Dockery, Bonita; Dismukes, William E.; Stevens, David A.

In: American Journal of Medicine, Vol. 97, No. 2, 1994, p. 135-144.

Research output: Contribution to journalArticle

Denning, DW, Lee, JY, Hostetler, JS, Pappas, P, Kauffman, CA, Dewsnup, DH, Galgiani, JN, Graybill, JR, Sugar, AM, Catanzaro, A, Gallis, H, Perfect, JR, Dockery, B, Dismukes, WE & Stevens, DA 1994, 'NIAID mycoses study group multicenter trial of oral itraconazole therapy for invasive aspergillosis', American Journal of Medicine, vol. 97, no. 2, pp. 135-144. https://doi.org/10.1016/0002-9343(94)90023-X
Denning, David W. ; Lee, Jeanette Y. ; Hostetler, John S. ; Pappas, Peter ; Kauffman, Carol A. ; Dewsnup, Daniel H. ; Galgiani, John N ; Graybill, John R. ; Sugar, Alan M. ; Catanzaro, Antonino ; Gallis, Harry ; Perfect, John R. ; Dockery, Bonita ; Dismukes, William E. ; Stevens, David A. / NIAID mycoses study group multicenter trial of oral itraconazole therapy for invasive aspergillosis. In: American Journal of Medicine. 1994 ; Vol. 97, No. 2. pp. 135-144.
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abstract = "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.",
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T1 - NIAID mycoses study group multicenter trial of oral itraconazole therapy for invasive aspergillosis

AU - Denning, David W.

AU - Lee, Jeanette Y.

AU - Hostetler, John S.

AU - Pappas, Peter

AU - Kauffman, Carol A.

AU - Dewsnup, Daniel H.

AU - Galgiani, John N

AU - Graybill, John R.

AU - Sugar, Alan M.

AU - Catanzaro, Antonino

AU - Gallis, Harry

AU - Perfect, John R.

AU - Dockery, Bonita

AU - Dismukes, William E.

AU - Stevens, David A.

PY - 1994

Y1 - 1994

N2 - 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.

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