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Int J Antimicrob Agents. 2006 Nov;28(5):439-49. Epub 2006 Oct 19.

The concentration-dependent nature of in vitro amphotericin B-itraconazole interaction against Aspergillus fumigatus: isobolographic and response surface analysis of complex pharmacodynamic interactions.

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National Cancer Institute, Pediatric Oncology Branch, Bethesda, MD 20892, USA.


The interaction between polyenes and azoles is not well understood. We therefore explored the in vitro combination of amphotericin B with itraconazole against 14 clinical Aspergillus fumigatus isolates (9 itraconazole susceptible and 5 itraconazole resistant) with a colorimetric broth microdilution checkerboard technique using two drug interaction models able to explore complicated patterns of interactions: the response surface analysis of Bliss independence and the isobolographic analysis of Loewe additivity zero interaction theories. Synergy was found at combinations with low concentrations of amphotericin B (<0.125 mg/L), whereas antagonism was found at combinations with higher concentrations of amphotericin B. For itraconazole-resistant isolates, synergistic interactions were observed at high concentrations of itraconazole (>0.5 mg/L). Synergy was more frequently observed for the itraconazole-resistant isolates than for the itraconazole-susceptible isolates.

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