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Using a Sequential Regimen to Eliminate Bacteria at Sublethal Antibiotic Dosages

Fig 1

At IC50 dosages, population recovery is fastest for the 50/50 combination treatment and slowest for a sequential treatment.

(A) Mean densities are shown at the end of each season for all sequential treatments at IC50 (as blue and green dots) and for the 50/50 combination of both drugs (black dotted line). The treatment maximising inhibition in season 1 (at 12 h) is the 50/50 combination treatment, because of the synergy. However, by season 8 (at 96 h), all sequential treatments produce lower mean densities than the 50/50 treatment, out of which the lowest density obtained from all the treatments tested is indicated by red circles. Also shown are mean final densities (see x-label “means”) of the 50/50 treatment (black circle), the best sequential treatment (red circle), and of all sequential treatments (green circle ± SE, three replicates per treatment). (B) A forest plot showing densities obtained using different sequential treatments at 96 h relative to the 50/50 treatment (drug orders are illustrated by the blue and green boxes on the left). The vertical black line represents the mean density for the 50/50 combination, the vertical dashed line is the mean of all the sequential treatments, and the dots mark the deviation in density produced from the 50/50 combination treatment (± SE, n = 3). Like (A), this shows that the combination treatment performs at the poorest extreme of the distribution of all sequential treatments measured in terms of how bacterial growth is suppressed by 96 h. There is no evidence of bacterial clearance in any treatment. (S1 Data contains the data used in this figure.)

Fig 1

doi: https://doi.org/10.1371/journal.pbio.1002104.g001