Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome

Joseph Wheat, Richard Hafner, Ann H. Korzun, Maria Theresa Limj, Patricia Spencer, Robert A. Larsen, Frederick M. Hecht, William Powderly

Research output: Contribution to journalArticle

203 Scopus citations

Abstract

purpose: Amphotericin B has been the treatment of choice for disseminated histoplasmosis in patiente with acquired immunodeficiency syndrome (AIDS). Oral antifungal agents would be welcome alternatives to standard treatment of disseminated histoplasmosis in less severe cases. The purpose of this study was to assess the efficacy and safety of itraconazole therapy in patients with AIDS and disseminated histoplasmosis. patients and methods: This was a multicenter, open-label, nonrandomized prospective trial conducted in university hospitals of the AIDS Clinical Trial Group. All patients had AIDS and first episodes of disseminated histoplasmosis. Patients with central nervous system involvement or with severe clinical manifestations were excluded. Patients were treated with itraconazole bid by mouth 300 mg for 3 days and then 200 mg bid for 12 weeks. Resolution of clinical findings, clearance of positive cultures, and drug tolerance were the main outcome measurements. A secondary objective was effect of therapy on Histoplasma capsutatum var capsulation antigen levels. results: Of 59 evaluable patients, 50 (85%) responded to therapy. Five patients withdrew because of progressive infection, 1 died of a presumed pulmonary embolus within the first week of therapy without improvement, 2 withdrew because of toxicity, and 1 was lost to follow-up after week 2 of therapy. Patients with moderately severe clinical (fever >39.5 °C or Karnofsky score <60) or laboratory abnormalities (alkaline phosphatase >5 times normal or albumin <3 g/dL) at baseline tended to respond more poorly than did other patients. Resolution of complaints of fever and improvement in fatigue occurred after a median of 3 and 6 weeks, respectively, and weight gain after 2 weeks. Fungemia cleared after a median of 1 week. H capsulatum var capsulatum antigen cleared from the urine and serum at rates of 0.2 and 0.3 units per week, respectively. conclusions: Itraconazole is safe and effective induction therapy for mild disseminated histoplasmosis in patients with AIDS, offering an alternative to amphotericin B in such cases. Patients with moderately severe or severe histoplasmosis should first be treated with amphotericin B and then may be switched to itraconazole after achieving clinical improvement.

Original languageEnglish
Pages (from-to)336-342
Number of pages7
JournalThe American journal of medicine
Volume98
Issue number4
DOIs
StatePublished - Apr 1995

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