TITLE

Triazole-Polyene Antagonism in Experimental Invasive Pulmonary Aspergillosis: In Vitro and In Vivo Correlation

AUTHOR(S)
Meletiadis, Joseph; Petraitis, Vidmantas; Petraitiene, Ruta; Pengxin Lin; Stergiopoulou, Theodouli; Kelaher, Amy M.; Tin Sein; Schaufele, Robert L.; Bacher, John; Walsh, Thomas J.
PUB. DATE
October 2006
SOURCE
Journal of Infectious Diseases;10/1/2006, Vol. 194 Issue 7, p1008
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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.
ACCESSION #
22251253

 

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