Surface Response Modeling to Examine the Combination of Amphotericin B Deoxycholate and 5-Fluorocytosine for Treatment of Invasive Candidiasis

Hope, William W.; Warn, Peter A.; Sharp, Andrew; Reed, Paul; Keevil, Brian; Louie, Arnold; Denning, David W.; Drusano, George L.
August 2005
Journal of Infectious Diseases;8/15/2005, Vol. 192 Issue 4, p673
Academic Journal
The strategy of combining antifungal drugs in a treatment regimen may improve the outcome of invasive candidiasis. Using a well-validated pharmaco dynamic murine model of invasive candidiasis, we defined the effect of the combination of amphotericin B deoxycholate (AmB) and 5-fluorocytosine (5FC) by use of the Greco model of drug interaction. The combination was additive, meaning that the experimental effect did not deviate in a statistically significant manner from the null reference model (or additive surface) of the combined effect. From a clinical perspective, the addition of 5FC to a regimen of AmB may enable the near-maximum effect to be reached in circumstances in which the administration of a given dose of AmB alone produces a submaximum effect but an increase in the dose is not possible, because of dose-related toxicity. Our methods provide a way in which some of the complex issues surrounding antifungal combination treatment can be addressed.


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