Literature DB >> 8059779

NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis.

D W Denning1, J Y Lee, J S Hostetler, P Pappas, C A Kauffman, D H Dewsnup, J N Galgiani, J R Graybill, A M Sugar, A Catanzaro.   

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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Year:  1994        PMID: 8059779     DOI: 10.1016/0002-9343(94)90023-x

Source DB:  PubMed          Journal:  Am J Med        ISSN: 0002-9343            Impact factor:   4.965


  70 in total

1.  In vitro activity of Syn-2869, a novel triazole agent, against emerging and less common mold pathogens.

Authors:  E M Johnson; A Szekely; D W Warnock
Journal:  Antimicrob Agents Chemother       Date:  1999-05       Impact factor: 5.191

2.  Tolerance and efficacy of Amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in haematological patients.

Authors:  Z Erjavec; G M Woolthuis; H G de Vries-Hospers; W J Sluiter; S M Daenen; B de Pauw; M R Halie
Journal:  Eur J Clin Microbiol Infect Dis       Date:  1997-05       Impact factor: 3.267

Review 3.  Triazole antifungal agents in invasive fungal infections: a comparative review.

Authors:  Cornelia Lass-Flörl
Journal:  Drugs       Date:  2011-12-24       Impact factor: 9.546

4.  Efficacy of caspofungin as salvage therapy for invasive aspergillosis compared to standard therapy in a historical cohort.

Authors:  J W Hiemenz; I I Raad; J A Maertens; R Y Hachem; A J Saah; C A Sable; J A Chodakewitz; M E Severino; P Saddier; R S Berman; D M Ryan; M J Dinubile; T F Patterson; D W Denning; T J Walsh
Journal:  Eur J Clin Microbiol Infect Dis       Date:  2010-08-12       Impact factor: 3.267

Review 5.  Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis.

Authors:  S B Girois; F Chapuis; E Decullier; B G P Revol
Journal:  Eur J Clin Microbiol Infect Dis       Date:  2006-02       Impact factor: 3.267

Review 6.  Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis.

Authors:  S B Girois; F Chapuis; E Decullier; B G P Revol
Journal:  Eur J Clin Microbiol Infect Dis       Date:  2005-02       Impact factor: 3.267

7.  Economic evaluation of intravenous itraconazole for presumed systemic fungal infections in neutropenic patients in Korea.

Authors:  K Moeremans; L Annemans; Ji-So Ryu; Kang-Won Choe; Wan-Shik Shine
Journal:  Int J Hematol       Date:  2005-10       Impact factor: 2.490

Review 8.  [Update: invasive fungal infections: Diagnosis and treatment in surgical intensive care medicine].

Authors:  C Lichtenstern; S Swoboda; M Hirschburger; E Domann; T Hoppe-Tichy; M Winkler; C Lass-Flörl; M A Weigand
Journal:  Anaesthesist       Date:  2010-01       Impact factor: 1.041

9.  An economic evaluation of voriconazole versus amphotericin B for the treatment of invasive aspergillosis in Canada.

Authors:  Coleman Rotstein; Michel Laverdière; Anne Marciniak; Farzad Ali
Journal:  Can J Infect Dis Med Microbiol       Date:  2004-09       Impact factor: 2.471

Review 10.  Treatment of invasive Aspergillosis in children with hematologic malignancies.

Authors:  Walid Abuhammour; Rashed A Hasan
Journal:  Indian J Pediatr       Date:  2004-09       Impact factor: 1.967

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