Synergy was calculated using the MacSynergy II software developed by Prichard and Shipman, which was modified to accommodate a three-drug combination [12] and is similar to that reported previously describing this approach [13] . The theoretical additive interactions were calculated from the concentrationresponse curves of each drug as a single agent. This calculated additive surface was then subtracted from the observed, experimental surface to reveal regions that deviate from the calculated additive effects. Purely additive interactions are represented graphically as areas in grey, indicating that they do not differ from the calculated additive effects. Synergistic interactions result in greater inhibition than the calculated inhibition, and are represented as areas in blue. Conversely, antagonism is represented as areas in red. Synergy plots are shown as the percent inhibition above or below expected (calculated additive inhibition), and are presented as the mean of three replicates at a level of 95% confidence, which eliminates insignificant deviations from the additive surface.