Comparative In Vitro Killing of Key Bovine Respiratory Bacterial Pathogens by Pradofloxacin and Eight Other Veterinary Antimicrobial Agents

Pradofloxacin is a third-generation dual enzyme targeting bactericidal veterinary fluoroquinolone, recently approved for use in cattle for bovine respiratory disease, which is active against Gram-positive/negative, atypical and anaerobic bacteria. We compared in vitro killing by pradofloxacin to that by ceftiofur, danofloxacin, enrofloxacin, florfenicol, marbofloxacin, tildipirosin, tilmicosin and tulathromycin against bovine isolates of <i>Mannheimia haemolytica</i> and <i>Pasteurella multocida</i> over a range of bacterial densities (10⁶-10⁹ cfu/mL). Drug concentrations used in the kill assays included the minimum inhibitory and mutant prevention drug concentrations and maximum serum and maximum tissue drug concentrations. Regardless of bacteria density tested and drug concentration used, pradofloxacin consistently killed as many or more (but not fewer) bacterial cells than any other drug tested against <i>M. haemolytica</i> strains. At the 10⁸-10⁹ cfu/mL densities, pradofloxacin killed 99-99.9%, 100% and 100% of bacterial cells at the MPC, maximum serum and maximum tissue drug concentrations, respectively, following 24 h of drug exposure. Indeed, pradofloxacin killed 99.9-99.99% of cells following 30-60 min of exposure to the maximum serum concentration. Similar trends were seen with killing of <i>P. multocida</i> strains by pradofloxacin. Against high-density bacterial populations, pradofloxacin was rapidly bactericidal and consistently killed more cells than the other agents tested. This manuscript represents the most comprehensive comparative in vitro kill study completed to date.