1989The American Journal of MedicineOpen access

Treatment of invasive aspergillosis with itraconazole

David W. Denning, RICHARD M. TUCKER, Linda Hansen, David A. Stevens

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Abstract

PURPOSE: Invasive aspergillosis in the immunocompromised host is one of the most difficult therapeutic problems. Itraconazole, a new oral triazole, is inhibitory as well as fungicidal against Aspergillus species in vitro. It is active against Aspergillus infections in animal models. We present our experience with itraconazole therapy of 21 patients with aspergillosis. PATIENTS AND METHODS: Eighteen of the 21 patients received 400 mg of itraconazole orally per day; the other three received 100 to 200 mg daily. Serum concentrations of itraconazole were measured and susceptibility testing was performed according to previously described methods. RESULTS: Of 15 evaluable patients, responses were produced in 12. Four of five with invasive pulmonary disease, two of two with skeletal disease, one of two with pleural disease, one of one with pericardial, sinus, mastoid, or hepatosplenic aspergillosis, and one of one with onychomycosis responded. One patient with carotid artery disease did not show a response, although results of cultures were negative at autopsy. One responder with joint disease had a possible relapse three months after completing 12 months of therapy. Ten of these patients were immunocompromised (including four with neutropenia and two renal transplant recipients) and eight of these responded. Side effects with itraconazole, in contrast to previously available therapy, were rare. CONCLUSION: This experience suggests itraconazole may be an important advance in the therapy of aspergillosis.

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PURPOSE: Invasive aspergillosis in the immunocompromised host is one of the most difficult therapeutic problems. Itraconazole, a new oral triazole, is inhibitory as well as fungicidal against Aspergillus species in vitro. It is active against Aspergillus infections in animal models. We present our experience with itraconazole therapy of 21 patients with aspergillosis. PATIENTS AND METHODS: Eighteen of the 21 patients received 400 mg of itraconazole orally per day; the other three received 100 to 200 mg daily. Serum concentrations of itraconazole were measured and susceptibility testing was performed according to previously described methods. RESULTS: Of 15 evaluable patients, responses were produced in 12. Four of five with invasive pulmonary disease, two of two with skeletal disease, one of two with pleural disease, one of one with pericardial, sinus, mastoid, or hepatosplenic aspergillosis, and one of one with onychomycosis responded. One patient with carotid artery disease did not show a response, although results of cultures were negative at autopsy. One responder with joint disease had a possible relapse three months after completing 12 months of therapy. Ten of these patients were immunocompromised (including four with neutropenia and two renal transplant recipients) and eight of these responded. Side effects with itraconazole, in contrast to previously available therapy, were rare. CONCLUSION: This experience suggests itraconazole may be an important advance in the therapy of aspergillosis.

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Available abstract

PURPOSE: Invasive aspergillosis in the immunocompromised host is one of the most difficult therapeutic problems. Itraconazole, a new oral triazole, is inhibitory as well as fungicidal against Aspergillus species in vitro. It is active against Aspergillus infections in animal models. We present our experience with itraconazole therapy of 21 patients with aspergillosis. PATIENTS AND METHODS: Eighteen of the 21 patients received 400 mg of itraconazole orally per day; the other three received 100 to 200 mg daily. Serum concentrations of itraconazole were measured and susceptibility testing was performed according to previously described methods. RESULTS: Of 15 evaluable patients, responses were produced in 12. Four of five with invasive pulmonary disease, two of two with skeletal disease, one of two with pleural disease, one of one with pericardial, sinus, mastoid, or hepatosplenic aspergillosis, and one of one with onychomycosis responded. One patient with carotid artery disease did not show a response, although results of cultures were negative at autopsy. One responder with joint disease had a possible relapse three months after completing 12 months of therapy. Ten of these patients were immunocompromised (including four with neutropenia and two renal transplant recipients) and eight of these responded. Side effects with itraconazole, in contrast to previously available therapy, were rare. CONCLUSION: This experience suggests itraconazole may be an important advance in the therapy of aspergillosis.

Key concepts: Itraconazole, Medicine, Aspergillosis, Neutropenia, Mycosis, Internal medicine, Aspergillus, Amphotericin B

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