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

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

Journal of Infectious Diseases 194(7): 1008-1018

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.

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Accession: 012711296

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PMID: 16960790

DOI: 10.1086/506617

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