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Using a Sequential Regimen to Eliminate Bacteria at Sublethal Antibiotic Dosages

Fig 2

Some examples of successful sequential treatments at IC70 dosages.

(A) This Manhattan plot at IC70 shows the mean total optical densities observed during eight seasons of treatment (Σ0D(T) on the vertical axis, vertical lines are SE, and n = 3). Note the 16 treatments marked with a red or black square: they had among the lowest final densities of the treatments trialled. After this, the 16 treatments were replicated; a red square shows that a zero cell density was observed in all three initial and subsequent replicates of that treatment, and black squares show a zero population density was observed in some, but not all, replicates. (B) The no-drug, ERY, and DOX monotherapies and the 50/50 combination treatment all produce recovering mean population densities at IC70 doses. These four unsuccessful treatments are shown next to the optical density dynamics of three replicates of a successful “red square” treatment from (A) (treatment C in panel C). The three replicates (shown as grey lines with blue [DOX] and green [ERY] circles) indicate parallel dynamics and fluctuating decay towards zero (bars are SE of optical density at 96 h, n = 3). (C) Season-by-season mean densities of all the successful (red square) treatments from (A); note how two achieve high densities early during treatment. Fig S15 in S1 Text, section 3, shows colony-forming units for replicates of these treatments. (S1 Data contains the data used in this figure.)

Fig 2