Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: A Collaborative Study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group

Raoul Herbrecht, Thomas F. Patterson, Monica A. Slavin, Oscar Marchetti, Johan Maertens, Elizabeth M. Johnson, Haran T. Schlamm, J. Peter Donnelly, Peter G. Pappas

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Background. Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. Methods. The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged. Results. Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. Conclusions. Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA.

Original languageEnglish (US)
Pages (from-to)713-720
Number of pages8
JournalClinical Infectious Diseases
Volume60
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Amphotericin B
  • Neutropenia
  • Preemptive therapy
  • Voriconazole

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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