Effect of varying antibiotic and phage timing and concentration when the erythromycin-resistant bacterial strain (B_E) is in minority (10⁶ cfu/mL).

a-b) Varying timing (x-axis) and dose of antibiotic and phage (y-axis) affects total bacterial count after 48h (top), maximum concentration of double-resistant bacteria (BET) (middle), and time when the concentration of BETis greater than 1 colony-forming unit (cfu) per mL (bottom). a) Adding 108 plaque-forming units (pfu) per mL of phage, and between 0.2 and 2.2 mg/L of both erythromycin and tetracycline. b) Adding 1 mg/L of both erythromycin and tetracycline, and between 105 and 1010 pfu/mL of phage. The x-axis indicates the time when antibiotics were added, relative to when phage were added. For example, the value “4” indicates that phage were present at the start of the simulation, and antibiotics were introduced 4h later. The segments with black borders correspond to the dynamics shown in c). c) Phage and bacteria dynamics over 48h for 4 conditions taken from panel b. In all 4 conditions, indicated by the black rectangles, phage are initially present at a concentration of 108 pfu/mL, while erythromycin and tetracycline are both introduced at concentrations of 1 mg/L after either 0h, 3h, 5h or 15h, stated on the plots, with the timing indicated by the vertical dashed lines. Horizontal dotted lines indicate bacteria remaining after 48h (corresponding to the top row of a-b) and maximum double-resistant bacteria (BET) concentration (middle row of a-b). Solid line indicates the detection threshold of 1 cfu or pfu/mL. (TIF)