The combination of penicillin and novobiocin is currently available for the treatment of bovine mastitis, but methods are not available for susceptibility testing of the combination by veterinary diagnostic laboratories. The minimum inhibitory concentration (MIC) and disk diffusion data were determined for penicillin, novobiocin, and a combination of the two in a 1:2 ratio for 225 staphylococcal, streptococcal, and Gram-negative isolates from bovine intramammary infections. Based on the drug concentrations in milk following infusion, linear regression analysis, and error rate bounding, the interpretive zone diameters selected were < or = 16 mm for resistant isolates and > or 17 mm for susceptible isolates with a disk containing 10 U of penicillin and 30 micrograms of novobiocin. Additionally, MIC breakpoints of < or = 2 micrograms/ml of penicillin and 4 micrograms/ml of novobiocin were selected to categorize isolates as susceptible and > or = 4 micrograms/ml of penicillin and 8 micrograms/ml of novobiocin were selected to categorize isolates as resistant. The MIC and disk diffusion results, as well as studies to monitor bacterial killing by antimicrobial agents over time, indicated that the combination of penicillin and novobiocin in a 1:2 ratio was more active than were the individual drugs. Kinetics of the kill curves with the penicillin and novobiocin combination (1:2 ratio) showed that the combination was bactericidal for Staphylococcus aureus and Staphylococcus xylosus.

Abstract. Ceftiofur, an extended-spectrum cephalosporin, is active against a variety of animal pathogens, including organisms associated with swine respiratory disease. However, minimum inhibitory concentration (MIC) breakpoint and disk diffusion interpretive criteria have not been established for swine pathogens. Susceptibility tests were performed by broth microdilution MIC and disk diffusion methods on 246 bacterial species that cause swine respiratory disease. Ceftiofur was active against Salmonella sp., Pasteurella multocida, Actinobacillus pleuropneumoniae, Streptococcus suis, and Escherichia coli but was not active against Bordetella bronchiseptica measured by MIC. Based on pharmacokinetic studies of ceftiofur in swine after a single intramuscular injection of 3 or 5 mg/kg body weight of ceftiofur and on the MIC and disk diffusion data, we recommend MIC breakpoints and disk diffusion distances, respectively, of ≤ 2 µg/ml and ≥ 21 mm for susceptible, 4 µg/ml and 18-20 mm for intermediate, and ≥ 8 µg/ml and ≤ 17 mm for resistant classification for swine pathogens. When these breakpoints were applied to data from a previous study using bovine pathogens, only 1 minor interpretive error occurred.Swine respiratory disease is an economically important disease to swine producers 1,13 . The etiology of swine respiratory disease is complex; it may be caused by a variety of organisms, either alone or in combination, but the species commonly implicated include Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, Escherichia coli, Streptococcus suis, and Mycoplasma hyopneumoniae. 1,12,13 Antimicrobial therapy is an important component of programs to reduce both the morbidity and mortality associated with swine respiratory disease. 1,12,13 Ceftiofur is an extended-spectrum cephalosporin that is active against a variety of animal pathogens. 15 It was approved by the Food and Drug Administration in 1988 for use in the treatment of bovine respiratory disease. At that time, minimum inhibitory concentration (MIC) breakpoint and zone interpretive criteria were recommended based upon the microbiology and the pharmacokinetics of ceftiofur in cattle. The MIC breakpoints and zone diameters, respectively, were ≤ 2 µg/ml and ≥ 24 mm for susceptible, 4 µg/ml and 20-23 mm for intermediate, and ≥ 8 µg/ml and ≤ 19 mm for resistant designations. Recently, ceftiofur has also been approved for the treatment of swine respiratory Received for publication September 29, 1995. disease with a dose range of 3-5 mg/kg/day, but MIC breakpoints and zone interpretive criteria have not been established. The purpose of this study was to establish interpretive criteria for swine respiratory disease pathogens based upon the pharmacokinetics of ceftiofur in swine, broth microdilution MIC, and agar disk diffusion data generated for swine pathogens. Materials and methodsBacterial strains. The 246 bacterial isolates used in this study were obtained from Pharmacia and Upjohn (Kalamazoo, MI) and from Lorraine Hoffman at the Vet...