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When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load: The Smile-Frown Transition

Figure 9

The stronger the synergy on day 1, the stronger the antagonism on day 2, both in models and data.

(a) A theoretical model trained on prior predicts that the difference between 18 h synergy and 42 h antagonism will be greater at greater doses. (The prior training data is included in one of the panes and basal dosages are given within each pane.) (b) Predicted changes in interaction are shown as blue points that were determined using α values from the simulations in (a) above. Alongside these are the analogous α values from data in (c) which are black, the dashed line is the linear regression from (c). (c) The correlation between day 1 synergy and day 2 antagonism measured empirically at different basal dosages can be seen in this linear regression showing the interaction measure α at 12 h versus α at 48 h (see Materials and Methods for the definition of α; horizontal and vertical lines are s.e.). Labels denote the level of growth inhibition, 40, 80, 90 and 95%, observed at 18 h relative to a zero-drug control for each of four basal drug dosages.

Figure 9