Exposure of 10⁶ cfu/mL of P. multocida to the MIC drug concentrations of the eight antimicrobial agents tested yielded the following results (Table 2): Pradofloxacin killed 11.2–26.9% of cells following 30 min to 2 h of drug exposure, 97.7% following 4 h and 98.8% following 24 h. By comparison, marbofloxacin killed up to 8.7% of cells following 2 h of drug exposure, 90.5% following 4 h, and 9.6% after 24 h of drug exposure. Tildipirosin killed 34.8–49.1% of cells following 4–6 h of drug exposure and 88.1% and 90.5% following 12 and 24 h of drug exposure. For ceftiofur, between 15.7% to 72.2% of cells were killed following 30 min to 6 h of drug exposure, following which regrowth occurred. Minimal or no killing occurred in the presence of the other drugs. Statistically significant differences in kill rate were not seen between any agents following 30 min, 1, 2, 4, 6, and 12 h of drug exposure. Following 24 h of drug exposure, pradofloxacin (4.1 log₁₀, 98.8% kill) killed more cells than ceftiofur (growth, p < 0.001), enrofloxacin (growth, p < 0.0001), tildipirosin (1.2 log₁₀, 90.5% kill, p = 0.0002), tilmicosin (growth, p ≤ 0.0001), and tulathromycin (growth, p < 0.0001). Regarding time, significant differences were seen in treatment (p = 0.0217), time (p < 0.0001), and treatment by time (p < 0.0001).

Exposure of 10⁷ cfu/mL of P. multocida to the MIC drug concentrations did not result in any significant differences in kill rates between the drug tested following 30 min, 1, 2, 4, 6, and 12 h of drug exposure (Table 3). Pradofloxacin killed up to 87.8% of cells following 12 h for drug exposure as compared to up to 49.4% by ceftiofur following 6 h of drug exposure. Minimal or no killing occurred in the presence of the other agents, and growth or regrowth occurred with all drugs. Following 24 h of drug exposure, pradofloxacin (4.1 log₁₀) killed more cells than ceftiofur (growth, p < 0.0001), enrofloxacin (growth, p < 0.0001), marbofloxacin (growth, p < 0.0001), tildipirosin (1.2 log₁₀, p = 0.0003), tilmicosin (growth, p < 0.0001), and tulathromycin (growth, p < 0.0001). For time, statistically significant differences were seen for treatment (p = 0.0380) and treatment by time (p < 0.001).

Exposure of 10⁸ cfu/mL of P. multocida to the MIC drug concentrations did not result in significant differences in kill rates between the drugs following 30 min, 1, 2, 4, 6, and 12 h of drug exposure (Table 4). Pradofloxacin killed between 43.6 and 60.5% of cells following 30 min to 4 h of drug exposure. Minimal or no killing was seen with the other agents over these same time points. Following 24 h of drug exposure, pradofloxacin (1.6 log₁₀) killed more cells than ceftiofur (growth, p = 0.0189), florfenicol (growth, p = 0.0272), marbofloxacin (growth, p = 0.0005), tildipirosin (growth, p = 0.0015), tilmicosin (0.04 log₁₀, p = 0.0354), and tulathromycin (growth, p = 0.0066). For time, a statistically significant difference was seen for treatment by time (p = 0.0010).

Exposure of 10⁹ cfu/mL of P. multocida to the MIC drug concentrations did not result in statistically significant differences in kill rates between the drugs following 30 min, 1, 2, 4, 6, 12, and 24 h of drug exposure (Table 5). Killing was minimal by all agents with killing between growth to 31.9% kill following 24 h of drug exposure. No statistically significant differences were seen for treatment by time.

Exposure of 10⁶ cfu/mL of MPC drug concentrations of the eight antimicrobial agents tested yielded the following results (Table 2): Pradofloxacin killed 56.7% of cells following 30 min of drug exposure, which increased to 96.9% following 4 h and 99.9% following 24 h of drug exposure. For enrofloxacin and marbofloxacin, growth to 41.9% kill was seen following 30 min of drug exposure, which increased to 89.5–90.9% after 4 h and 70.4–99.8% after 24 h of drug exposure. Ceftiofur killed the following percentage of cells following 30 min, 4 h, and 24 h of drug exposure: 8.6%, 75.8%, and 99.6%. Florfenicol killed up to 53.8% of cells following 6 h of drug exposure but growth occurred thereafter. For tildipirosin, tilmicosin, and tulathromycin, the following percentages of cells were killed following 30 min, 4 h, and 24 after of drug exposure: growth to 31.4%, 32.7–82.6%, and 99.4–99.9%. Statistically significant differences in kill rates were not seen between agents following 30 min, 1, 2, 4, 6, and 12 h of drug exposure. Following 24 h of drug exposure, ceftiofur (3.7 log₁₀, 99.6% kill) killed more cells than enrofloxacin (0.8 log₁₀, 70.4% kill, p = 0.0514). Pradofloxacin (5.2 log₁₀, 99.9% kill) killed more cells than enrofloxacin (p < 0.0001), florfenicol (0.9 log₁₀, p < 0.0001), and tulathromycin (2.3 log₁₀, 99.4% kill, p = 0.0527). Marbofloxacin (4.8 log₁₀, 99.8% kill) killed more cells than florfenicol (p = 0.0009) and enrofloxacin (p = 0.0001). Statistically significant differences were seen for treatment (p = 0.0413), time (p < 0.0001) and treatment by time (p < 0.0001).

Following exposure of 10⁷ cfu/mL to the MPC drug concentrations, statistically significant differences in kill between the agents were not seen following 30 min, 1, 2, 4, 6, and 12 h of drug exposure (Table 3). Pradofloxacin killed 65.0% of cells following 30 min of drug exposure and increasing to 97.9% after 4 h and 99.9% after 24 h of drug exposure. The kill values, respectively, for enrofloxacin and marbofloxacin for the same time points were as follows: 27.5% and 65.3%, 77.6 and 45.9, and growth to 14.2%. Tulathromycin killed 39.7 and 36.9% of cells following 4 and 24 h of drug exposure. Tildipirosin killed 5.7%, 56.3%, and 99.6% of cells following 30 min, 4 h, and 24 h of drug exposure. Tilmicosin killed 64.3 and 61.7% of cells following 4 and 24 h of drug exposure. Following 24 h of drug exposure, pradofloxacin (4.6 log₁₀, 99.9% kill) killed more cells than ceftiofur (1.0 log₁₀, 89.7% kill, p = 0.0111), florfenicol (growth, p = 0.0002), and tulathromycin (1.0 log₁₀, 36.9% kill). Statistically significant differences were seen for time (p < 0.0001) and treatment by time (p = 0.0091).

Following exposure of 10⁸ and 10⁹ cfu/mL of P. multocida to the MPC drug concentrations, statistically significant differences in kill rates were not seen between the agents tested at any time point following drug exposure. For the 10⁸ cfu/mL experiments, pradofloxacin killed 65.9%, 96.3%, and 96.9% of cells following 30 min, 4 h, and 24 h of drug exposure (Table 4). Enrofloxacin killed up to 48.0% of cells following 1 h of drug exposure but killing declined thereafter. Similarly, marbofloxacin killed up to 72.2% following 2 h of drug exposure but killing declined thereafter such that by 24 h after drug exposure, 36.9% of cells were killed. Ceftiofur killed up to 47.5% of cells after 6 h of drug exposure, which decreased to 25.5% kill after 24 h of drug exposure. Growth occurred in the presence of florfenicol and tulathromycin over all time points, and for tildipirosin and tilmicosin, 30.3–37.8% of cells were killed following 24 h of drug exposure and not more at any earlier time point. A statistically significant difference was seen for time (p < 0.0001).

For the 10⁹ cfu/mL kill measurements, pradofloxacin killed 60.9%, 75.2%, and 83.4% of cells following 30 min, 6 h, and 24 h of drug exposure (Table 5). Growth to up to 44.8% kill occurred in the presence of enrofloxacin, florfenicol, marbofloxacin, and tildipirosin. For ceftiofur, 2.9%, 40.3%, and 78.8% of cells were killed following 30 min, 6 h, and 24 h of drug exposure. Growth occurred in the presence of tulathromycin over all time points, and tilmicosin killed up to 58.4% of cells following 6 h of drug exposure but killing declined thereafter such that 38.6% of cells were killed following 24 h of drug exposure. A statistically significant difference was seen for time (p = 0.0005).

Following exposure of 10⁶ cfu/mL of P. multocida to the maximum serum drug concentrations of the drugs tested did not result in significant differences in kill rates between the drugs following 30 min of drug exposure (Table 2). Pradofloxacin killed 98.8%, 99.9%, and 100% of cells following 30 min, 4 h, and 12 h for drug exposure; for enrofloxacin and marbofloxacin, those values, respectively, were 81.7% and 98.9%, 98.7% and 99.4%, and 100% and 99.9%. Ceftiofur killed 55.6% of cells following 30 min of drug exposure, which increased to 97.7% kill after 4 h and 99.99% kill after 24 h of drug exposure; those values for florfenicol at the same time points were growth 83.8% and 99.9%. Growth occurred in the presence of tilmicosin at all time points. Tulathromycin killed 66.5% and 93.8% of cells following 12 and 24 h of drug exposure and tildipirosin killed 40.5%, 99.3%, and 99.99% of cells following 6, 12, and 24 h of drug exposure. Following 1 h of drug exposure, marbofloxacin (2.5 log₁₀, 98.9% kill) killed more cells than florfenicol (0.1 log₁₀, 14.3% kill, p = 0.0361), tildipirosin (growth, p = 0.016), tilmicosin (growth, p = 0.0088), and tulathromycin (growth, p = 0.0118). Following 2 h of drug exposure, marbofloxacin (2.6 log₁₀, 99.3% kill) killed more cells than florfenicol (0.2 log₁₀, 16.7% kill, p = 0.0343), tildipirosin (growth, p = 0.0068), tilmicosin (growth, p = 0.0007), and tulathromycin (growth, p = 0.0017). Pradofloxacin (2.2 log₁₀, 99.2% kill) killed more cells than tilmicosin (p = 0.0092) and tulathromycin (p = 0.0309). Following 4 h of drug exposure, ceftiofur (2.0 log₁₀, 97.7% kill) killed more cells than tilmicosin (growth, p = 0.0249). Enrofloxacin (2.1 log₁₀, 98.7% kill) killed more cells than tilmicosin (p = 0.0162). Marbofloxacin (2.6 log₁₀, 99.4% kill) killed more cells than tildipirosin (0.3 log₁₀, 37.1% kill, p = 0.0038), tilmicosin (growth p < 0.0001), and tulathromycin (growth, p = 0.0002). Pradofloxacin (3.4 log₁₀, 99.9% kill) killed more cells than florfenicol (0.9 log₁₀, 83.8% kill, p = 0.0344), tildipirosin (p = 0.0001), tilmicosin (p < 0.0001), and tulathromycin (p < 0.0001). Following 6 h of drug exposure, ceftiofur (2.8 log₁₀, 99.7% kill) killed more cells than tildipirosin (0.3 log₁₀, 40.5% kill, p = 0.026), tilmicosin (growth, p < 0.0001), and tulathromycin (growth, p = 0.0084). Enrofloxacin (2.4 log₁₀, 99.6% kill) killed more cells than tilmicosin (p = 0.0004). Marbofloxacin (2.7 log₁₀, 99.9% kill) killed more cells than tildipirosin (p = 0.0219), tilmicosin (p < 0.0001), and tulathromycin (p = 0.0067). Pradofloxacin (3.9 log₁₀, 99.9% kill) killed more cells than florfenicol (0.9 log₁₀, 85.5% kill, p = 0.0006), tildipirosin (p < 0.0001), tilmicosin (p < 0.0001), and tulathromycin (p < 0.0001). Following 12 h of drug exposure, ceftiofur (4.3 log₁₀, 99.9% kill) killed more cells than tilmicosin (growth, p < 0.0001) and tulathromycin (0.06 log₁₀, 66.5% kill). Florfenicol (1.1 log₁₀, 79.6% kill) killed more cells than tilmicosin (p = 0.0132). Marbofloxacin (3.3 log₁₀, 99.8%) killed more cells than tilmicosin (p < 0.0001) and tulathromycin (p = 0.0027). Pradofloxacin (5.9 log₁₀, 100% kill) killed more cells than florfenicol (p < 0.0001), tildipirosin (2.5 log₁₀, 99.3% kill, p < 0.0001), tilmicosin (p < 0.0001), and tulathromycin p < 0.0001). Tildipirosin killed more cells than tilmicosin (p = 0.0001). Following 24 h of drug exposure, ceftiofur (5.4 log₁₀, 99.99% kill) killed more cells than tilmicosin (growth, p < 0.0001) and tulathromycin (1.9 log₁₀, 93.8% kill, p < 0.0001). Enrofloxacin (6.6 log₁₀, 100% kill) killed more cells than florfenicol (4.0 log₁₀, 99.9% kill, p = 0.0086), tilmicosin (p < 0.0001), and tulathromycin (p < 0.0001). Marbofloxacin (6.5 log₁₀, 99.9% kill) killed more cells than florfenicol (p = 0.0377), tilmicosin (p < 0.0001), and tulathromycin (p < 0.0001). Pradofloxacin (6.7 log₁₀, 100% kill) killed more bacteria than florfenicol (p = 0.0048), tilmicosin (p < 0.0001) and tulathromycin (p < 0.0001). Tildipirosin (4.9 log₁₀, 99.99% kill) killed more cells than tilmicosin (p < 0.0001). Statistically significant differences were seen for treatment, time, and treatment by time (p values <0.0001) for all comparisons.

Following exposure of 10⁷ cfu/mL of P. multocida to the maximum serum concentrations of the drugs tested, statistically significant differences in kill rates were not seen between the agents following 30 min, 1, and 2 h of drug exposure (Table 3). Pradofloxacin killed 98.9%, 99.8%, and 100% of cells following 30 min, 4 h, and 24 after drug exposure; for enrofloxacin and marbofloxacin, those values were 83.4% and 98.5%, 99.5% and 99.45, and 99.8 and 100%. Ceftiofur killed 30.8, 94.3, and 92.4% of cells following 30 min, 4 h, and 24 h of drug exposure. Minimal killing (17.9%) but mostly growth occurred in the presence of tildipirosin, tilmicosin, and tulathromycin. Florfenicol killed 75.8% and 95.9% of cells following 12 and 24 h of drug exposure. Following 4 h of drug exposure, marbofloxacin (2.7 log₁₀, 99.4% kill) killed more cells than tulathromycin (growth, p = 0.0485). Pradofloxacin (2.8 log₁₀, 99.8% kill) killed more cells than tilmicosin (growth, p = 0.0377) and tulathromycin (growth, p = 0.0211) and approached a significant difference with tildipirosin (growth, p = 0.0575). Following 6 h of drug exposure, marbofloxacin (2.9 log₁₀, 99.7% kill) killed more cells than tildipirosin (growth, p = 0.0150), tilmicosin (growth, p = 0.0354), and tulathromycin (p = 0.0060). Pradofloxacin (2.9 log₁₀, 99.8% kill) killed more cells than tildipirosin (p = 0.0065), tilmicosin (p = 0.0093), and tulathromycin (p = 0.0027). Following 12 h of drug exposure, marbofloxacin (4.7 log₁₀, 99.99% kill) killed more cells than dd ceftiofur (1.5 log₁₀, 93.5% kill, p = 0.017), florfenicol (0.7 log₁₀, 75.8% kill, p < 0.0001), tildipirosin (0.3 log₁₀, 13% kill, p < 0.0001), tilmicosin (growth, p < 0.0001), and tulathromycin (growth, p < 0.000). Enrofloxacin (2.9 log₁₀, 99.8% kill) killed more cells than tilmicosin (p = 0.0313) and tulathromycin (p = 0.0003). Pradofloxacin (4.9 log₁₀, 99.9% kill) killed more cells than ceftiofur (p = 0.0017), florfenicol (p < 0.0001), tildipirosin (p < 0.0001), tilmicosin (p < 0.0001), and tulathromycin. Following 24 h of drug exposure, enrofloxacin (1.6 log₁₀) killed more cells than ceftiofur (2.2 log₁₀, 93.4% kill, p < 0.0001), florfenicol (1.7 log₁₀, 95.9% kill, p < 0.0001), tildipirosin (growth, p < 0.0001), tilmicosin (growth, p < 0.0001), and tulathromycin (growth, p < 0.0001). Marbofloxacin (7.0 log₁₀, 100% kill) killed more cells than ceftiofur (p < 0.0001), florfenicol (p < 0.0001), tildipirosin (p < 0.0001), tilmicosin (p < 0.0001), and tulathromycin (p < 0.0001). Pradofloxacin (7.8 log₁₀, 100% kill) killed more cells than ceftiofur (p < 0.0001), florfenicol (p < 0.0001), tildipirosin (p < 0.0001), tilmicosin (p < 0.0001), and tulathromycin (p < 0.0001). Statistically significant differences were seen for treatment, time, and treatment by time (p values <0.0001) for all comparisons.

Following exposure of 10⁸ cfu/mL of P. multocida to the maximum serum drug concentration of the eight drugs tested, statistically significant differences in kill rates between the drugs following 30 min, 1, and 2 h of drug exposure (Table 4). Pradofloxacin killed 98.6%, 99.9%, and 99.99% of cells following 30 min, 4 h, and 24 h of drug exposure; those values for enrofloxacin and marbofloxacin were 66.1 and 98.4, 96.1 and 99.9, and 99.8 and 99.9. For ceftiofur, 55.5%, 93.1%, and 96.0% of cells were killed following 30 min, 4 h, and 23 h of drug exposure. In the presence of florfenicol, tildipirosin, tilmicosin, and tulathromycin, the maximum kill was 47.8% (tildipirosin) following 12 h of drug exposure; however, growth occurred in the presence of all drugs at most time points. Following 4 h of drug exposure, marbofloxacin (3.5 log₁₀, 99.9% kill) killed more cells than tildipirosin (growth, p = 0.0404). Following 6 h of drug exposure, pradofloxacin (3.4 log₁₀, 99.9% kill) killed more cells than tildipirosin (growth, p = 0.0347). Following 12 h of drug exposure, pradofloxacin (5.8 log₁₀, 99.99% kill) killed more cells than ceftiofur (0.9 log₁₀, 84.9% kill, p = 0.0002), florfenicol (growth p < 0.0001), tildipirosin (growth, p < 0.0001), tilmicosin (growth, p < 0.0001), and tulathromycin (p < 0.0001). Following 24 h of drug exposure, pradofloxacin (5.9 log₁₀, 99.99% kill) killed more cells than ceftiofur (1.7 log₁₀, 96.0% kill, p = 0.0004), florfenicol (growth, p < 0.0001), tildipirosin (0.1 log₁₀, 16.7% kill, p < 0.0001), and tilmicosin (growth, p < 0.0001). Marbofloxacin (4.1 log₁₀, 99.9% kill) killed more cells than florfenicol (p = 0.0053), tildipirosin (p = 0.0082), and tilmicosin (p = 0.0127). Statistically significant differences were seen for treatment, time, and treatment by time (p values from 0.0018–<0.0001) for all comparisons.

Following exposure of 10⁹ cfu/mL of P. multocida to the maximum serum drug concentrations of the eight drugs tested, statistically significant differences in kill rates were not seen between the agents following 30 min, 1, 2, and 4 h following drug exposure (Table 5). Pradofloxacin killed 96.9% of cells following 30 min of drug exposure, which increased to 99.3% and 99.99% following 4 h and 24 h of drug exposure; for enrofloxacin and marbofloxacin, those values were, respectively, 84.9% and 95.7%, 98.2% and 98.4%, and 98.6% and 98.9%. Ceftiofur and florfenicol killed the following percentages of cells following 30 min, 4 h, and 24 h of drug exposure: 7.8% and 1%, 27.3% and 23.7%, and 95.6% and 63.5%. Growth occurred at all time points in the presence of tilmicosin, and 42.2% kill occurred following 24 h exposure to tildipirosin. Up to 46.3% kill occurred in the presence of tulathromycin following 12 h of drug exposure but regrowth occurred thereafter. Following 6 h of drug exposure, pradofloxacin (3.0 log₁₀, 99.7% kill) killed more cells than did tildipirosin (growth, p = 0.0245), tilmicosin (growth, p = 0.0191), and tulathromycin (growth, p = 0.0498). Following 12 h of drug exposure, pradofloxacin (3.0 log₁₀, 99.9% kill) killed more cells than florfenicol (growth, p = 0.0002), tildipirosin (growth, p = 0.0005), tilmicosin (growth, p = 0.0002), and tulathromycin (growth, p = 0.0232). Following 24 h of drug exposure, pradofloxacin (4.0 log₁₀, 99.99% kill) killed more cells than florfenicol (0.6 log₁₀, 63.5% kill, p < 0.0001), tildipirosin (0.4 log₁₀, 42.2% kill, p < 0.0001), tilmicosin (0.12 log₁₀, p < 0.0001), and tulathromycin (0.6 log₁₀, p < 0.0001). Statistically significant differences were seen for treatment, time, and treatment by time (p values from 0.0006–<0.0001) for all comparisons.

Following exposure of 10⁶ cfu/mL of P. multocida to the maximum tissue drug concentrations tested, statistically significant differences in kill rates between the agents were not seen following 30 min and 1 h of drug exposure (Table 2). Pradofloxacin killed 97.2%, 99.8%, and 99.99% of cells following 30 min, 2 h, and 12 h after drug exposure, and 100% after 24 h of drug exposure. Ceftiofur and enrofloxacin killed 55.3% and 75.2%, 60.9% and 98.3%, and 100% each following 30 min, 2 h, and 24 of drug exposure. Florfenicol killed 37.8% of cells following 1 h of drug exposure but growth occurred at all time points thereafter. Tildipirosin killed 3.6% of cells following 30 min of drug exposure, which increased to 25.7% and 99.9% following 2 and 24 h of drug exposure. Tulathromycin killed between 28.4 and 32.5% of cells following 4–6 h of drug exposure but regrowth occurred thereafter. Following 2 h of drug exposure, pradofloxacin (2.8 log₁₀, 99.8% kill) killed more cells than tildipirosin (0.2 log₁₀, 25.7% kill, p = 0.0370). Following 4 h of drug exposure, pradofloxacin (2.8 log₁₀, 99.4% kill) killed more cells than florfenicol (growth, p = 0.0179). Following 6 h of drug exposure, ceftiofur (2.9 log₁₀, 91.1% kill) killed more cells than florfenicol (0.2 log₁₀, p = 0.0370). Following 12 h of drug exposure, ceftiofur (4.1 log₁₀, 99.9% kill) killed more cells than florfenicol (0.4 log₁₀, p < 0.0001), tildipirosin (1.4 log₁₀, p = 0.0077), and tulathromycin (2.7 log₁₀, p = 0.0101). Enrofloxacin (3.2 log₁₀, 99.8% kill) killed more cells than florfenicol (p = 0.0062). Pradofloxacin (5.1 log₁₀, 99.99% kill) killed more cells than florfenicol (p < 0.0001), tildipirosin (p < 0.0001), and tulathromycin (p = 0.0001). Following 24 h of drug exposure, ceftiofur (3.8 log₁₀, 100% kill) killed more cells than florfenicol (1.5 log₁₀, p < 0.0001). Enrofloxacin (6.8 log₁₀, 100% kill) killed more cells than florfenicol (p < 0.0001) and tildipirosin (3.6 log₁₀, 99.9% kill, p = 0.0024). Pradofloxacin (6.9 log₁₀, 100% kill) killed more cells than florfenicol (p < 0.0001) and tildipirosin (3.6 log₁₀, 99.9% kill, p = 0.0008). Statistically significant differences were seen in treatment (p = 0.0001), time (p < 0.0001), and treatment by time (p < 0.0001).

Exposure of 10⁷ cfu/mL of P. multocida to the maximum tissue drug concentrations of the drugs tested did not result in significant differences in kill rates between drugs following 30 min of drug exposure (Table 3). Pradofloxacin killed 96.7%, 99.9%, and 100% of cells following 30 min, 6 h, and 24 h after drug exposure; for enrofloxacin, respectively, the values were 70.4%, 99.8%, and 100%. Ceftiofur and tildipirosin killed 50.7% and 4.1%, 97.7% and 56.2%, and 98.5% and 99.7% following 30 min, 6 h, and 24 h of drug exposure. Florfenicol killed 17.8% and 15.9% of cells following 30 min and 2 h of drug exposure but growth occurred at all other time points. Tulathromycin killed 10.2% and 25.8% of cells following 1–2 h of drug exposure and growth occurred at all other time points. Following 1 and 2 h of drug exposure, pradofloxacin (2.2–2.4 log₁₀, 97.8–99.1% kill) killed more cells than florfenicol (0.03 log₁₀, p = 0.0217, p = 0.0068). Following 4 h of drug exposure, enrofloxacin (2.1 log₁₀, 99.0% kill) and pradofloxacin (3.6 log₁₀, 99.4% kill) killed more cells than florfenicol (growth, p = 0.0223 and p = 0.0100). Pradofloxacin killed more cells than tildipirosin (0.2 log₁₀, 37.7% kill, p = 0.0100). Following 6 h of drug exposure, ceftiofur (1.9 log₁₀, 97.7% kill), enrofloxacin (2.8 log₁₀, 99.8% kill), and pradofloxacin (3.2 log₁₀, 99.9% kill) killed more cells than florfenicol (growth, p = 0.063, p < 0.0001, p < 0.0001). Enrofloxacin and pradofloxacin killed more cells than tildipirosin (0.4 log₁₀, 56.2% kill, pp = 0.0043 and p = 0.0043) and tulathromycin (growth, p = 0.0296 and p = 0.0282). Following 12 h of drug exposure, ceftiofur (2.2 log₁₀, 99.9%, p = 0.0015), enrofloxacin (3.8 log₁₀, 99.9% kill, p < 0.0001), and pradofloxacin (4.6 log₁₀, 99.99% kill, p < 0.0001) killed more cells than florfenicol (growth). Pradofloxacin killed more cells than ceftiofur (p = 0.0342). Enrofloxacin and pradofloxacin killed more cells than tildipirosin (1.2 log₁₀, 90.8% kill, p = 0.0016 and p < 0.0001) and tulathromycin (1.4 log₁₀, p < 0.0001 and p < 0.0001). Following 24 h of drug exposure, enrofloxacin (7.9 log₁₀, 100% kill) and pradofloxacin (7.5 log₁₀, 100% kill) killed more cells than ceftiofur (2.2 log₁₀, 98.5% kill, p < 0.0001 and p < 0.0001). Enrofloxacin and pradofloxacin killed more cells than florfenicol (0.6 log₁₀, p < 0.0001 and p < 0.0001). Enrofloxacin and pradofloxacin killed more cells than tildipirosin (2.9 log₁₀, 99.7% kill, p < 0.0001 and p < 0.0001) and tulathromycin (1.4 log₁₀, p < 0.0001 and p < 0.0001). Tildipirosin and tulathromycin killed more cells than florfenicol (p = 0.0004 and p = 0.0068). Statistically significant differences were seen for treatment, time, and treatment by time (p < 0.0001) for all comparisons.

Following exposure of 10⁸ cfu/mL of P. multocida to the maximum tissue drug concentration of the drugs tested, significant differences in kill rates between the drugs were not seen in the 30 min, 1 h, and 2 h following drug exposure (Table 4). Pradofloxacin killed 97.0%, 99.7%, and 99.99% of cells following 30 min, 4 h, and 24 h of drug exposure; for enrofloxacin, those values were 62.9%, 94.7%, and 97.1%. Maximal killing (47.6%) in the presence of florfenicol occurred following 24 h of drug exposure. Growth occurred at all time points in the presence of tulathromycin. Maximal killing (3.4%) in the presence of tildipirosin occurred following 24 h of drug exposure. Ceftiofur killed 32.9%, 78.1%, and 93.5% of cells following 30 min, 4 h, and 24 h of drug exposure. Following 4 h of drug exposure, pradofloxacin (3.1 log₁₀, 99.7% kill) killed more cells than tildipirosin (growth, p = 0.0313). Following 12 h of drug exposure, enrofloxacin (2.7 log₁₀, 97.7% kill) killed more cells than tulathromycin (growth, p = 0.0294) and pradofloxacin (3.6 log₁₀, 99.9% kill) killed more cells than tildipirosin (growth, p = 0.0019) and tulathromycin (p = 0.0001). Pradofloxacin killed more cells than florfenicol (growth, p = 0.0144). Following 24 h of drug exposure, pradofloxacin (4.5 log₁₀, 99.99% kill) killed more cells than ceftiofur (1.2 log₁₀, 93.5% kill, p = 0.0066), florfenicol (0.2 log₁₀, 47.6% kill, p = 0.0001), tildipirosin (0.1 log₁₀, 3.4% kill, p < 0.0001), and tulathromycin (growth, p < 0.0001). Enrofloxacin (2.9 log₁₀, 97.1% kill) killed more cells than tulathromycin (p = 0.0095). Statistically significant differences were seen for treatment, time, and treatment by time (p values from 0.0037–<0.0001) for all comparisons.

Following exposure of 10⁹ cfu/mL of P. multocida to the maximum tissue drug concentration of the drugs tested, statistically significant kill rates were not seen between the drugs following 30 min, 1, 2, 4, 6, and 12 h of drug exposure (Table 5). Pradofloxacin killed 73.6%, 94.2%, and 99.9% of cells following 30 min, 4 h, and 24 h of drug exposure; for enrofloxacin, those values were 36.9%, 62.1%, and 96.2%; for ceftiofur, those values were 4.5%, 13.7%, and 89.9%. Maximal killing (57.7%) in the presence of florfenicol occurred following 24 h of drug exposure. Minimal killing (4.4–14.9%) in the presence of tildipirosin and tulathromycin occurred following 30 min to 2 h following drug exposure, but growth occurred at all other time points for both drugs. Following 24 h of drug exposure, pradofloxacin (5.5 log₁₀, 99.9% kill) killed more cells than ceftiofur (1.1 log₁₀, 89.9% kill, p = 0.0004), enrofloxacin (1.6 log₁₀, 96.2% kill, p = 0.0019), florfenicol (0.5 log₁₀, 57.7% kill, p < 0.0001), tildipirosin (growth, p < 0.0001), and tulathromycin (growth, p < 0.0001). Statistically significant differences were seen for treatment, time, and treatment by time (p values from 0.0156–<0.0063) for all comparisons.