Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: In vitro and in vivo correlation

Joseph Meletiadis, Vidmantas Petraitis, Ruta Petraitiene, Pengxin Lin, Theodouli Stergiopoulou, Amy M. Kelaher, Tin Sein, Robert L. Schaufele, John Bacher, Thomas J. Walsh

Research output: Contribution to journalArticlepeer-review

Abstract

Combination antifungal therapy is increasingly used in the treatment of invasive aspergillosis. Whether the interaction between amphotericin B and triazoles is antagonistic against invasive aspergillosis is a controversial issue that is not likely to be resolved through a randomized clinical trial. Here, we found both in vitro and in vivo antagonism between liposomal amphotericin B and ravuconazole in simultaneous treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. Bliss independence-based drug-interaction modeling showed significant antagonism in vitro and in vivo, with the observed drug effects being 20%-69% lower than would be expected if the drugs were acting independently. These in vitro and in vivo findings of antagonism were consistent with the findings from Loewe additivity-based drug-interaction modeling. No pharmacokinetic interaction was found. The combination of a triazole and polyene may be antagonistic in the treatment of invasive pulmonary aspergillosis.

Original languageEnglish (US)
Pages (from-to)1008-1018
Number of pages11
JournalJournal of Infectious Diseases
Volume194
Issue number7
DOIs
StatePublished - Oct 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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