ceftiofur and Bovine-Respiratory-Disease-Complex

This study was designed to compare morbidity and mortality due to bovine respiratory disease (BRD) in 1,400 ranch-fresh, northern US calves that received either no metaphylaxis (MTX) (Group 1), MTX prompted by pen morbidity (Group 2), MTX prompted by a decline in feed intake (Group 3), or on-arrival MTX (Group 4). Ceftiofur crystalline free acid (6.6 mg/kg) was the MTX antimicrobial used. Decreased feed intake did not meet the study threshold, so Groups 1 and 3 were combined into a single control group. The percentage of calves not treated for BRD was 14% to 15% higher in Groups 4 and 2 (72.7% and 73.4%, respectively) compared with the controls (58.2%; P ≤ .02). Mortality was numerically higher in Group 2 (3.4%) compared with Groups 4 and 1 (0.9% and 1.6%, respectively). There were no differences in average daily gain or feed consumption. In northern, ranch-fresh calves, MTX as a health management practice reduces the incidence of BRD and has better utility when performed on arrival versus relying on morbidity as a signal for antimicrobial administration.

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cephalosporins; Drug Administration Schedule; Female

A total of 894 calves at high risk for bovine respiratory disease were processed at two sites and randomly assigned to receive one of three antimicrobial metaphylactic regimens to determine if a two-drug regimen offered any advantage over the more conventional one-course regimens. On arrival, calves received either a two-course regimen of ceftiofur crystalline free acid (CCFA) followed by tulathromycin 8 days later (Group 1) or a one-course regiment of CCFA (Group 2) or tilmicosin (Group 3). At Site A, morbidity was significantly lower (52%) in Group 1 than in Group 2 (76.3%) and Group 3 (78.4%). At Site B, morbidity was significantly lower in Group 1 (2.6%) than in Group 2 (9.4%) and Group 3 (7.2%).

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cephalosporins; Disaccharides; Drug Therapy, Combination; Heterocyclic Compounds; Male; Risk Factors; Treatment Outcome

Although 90% of BRD relapses are reported to receive retreatment with a different class of antimicrobial, studies examining the impact of antimicrobial selection (i.e. bactericidal or bacteriostatic) on retreatment outcomes and the emergence of antimicrobial resistance (AMR) are deficient in the published literature. This survey was conducted to determine the association between antimicrobial class selection for treatment and retreatment of BRD relapses on antimicrobial susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Pathogens were isolated from samples submitted to the Iowa State University Veterinary Diagnostic Laboratory from January 2013 to December 2015. A total of 781 isolates with corresponding animal case histories, including treatment protocols, were included in the analysis. Original susceptibility testing of these isolates for ceftiofur, danofloxacin, enrofloxacin, florfenicol, oxytetracycline, spectinomycin, tilmicosin, and tulathromycin was performed using Clinical and Laboratory Standards Institute guidelines. Data were analyzed using a Bayesian approach to evaluate whether retreatment with antimicrobials of different mechanistic classes (bactericidal or bacteriostatic) increased the probability of resistant BRD pathogen isolation in calves. The posterior distribution we calculated suggests that an increased number of treatments is associated with a greater probability of isolates resistant to at least one antimicrobial. Furthermore, the frequency of resistant BRD bacterial isolates was greater with retreatment using antimicrobials of different mechanistic classes than retreatment with the same class. Specifically, treatment protocols using a bacteriostatic drug first followed by retreatment with a bactericidal drug were associated with a higher frequency of resistant BRD pathogen isolation. In particular, first treatment with tulathromycin (bacteriostatic) followed by ceftiofur (bactericidal) was associated with the highest probability of resistant M. haemolytica among all antimicrobial combinations. These observations suggest that consideration should be given to antimicrobial pharmacodynamics when selecting drugs for retreatment of BRD. However, prospective studies are needed to determine the clinical relevance to antimicrobial stewardship programs in livestock production systems.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bovine Respiratory Disease Complex; Cattle; Cephalosporins; Disaccharides; Drug Resistance, Microbial; Fluoroquinolones; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Pasteurella multocida; Pasteurellaceae; Prospective Studies; Recurrence; Respiratory Tract Diseases; Serogroup; Tylosin

Antimicrobial drugs are used to treat pathogenic bacterial infections in animals and humans. The by-stander enteric bacteria of the treated host's intestine can become exposed to the drug or its metabolites reaching the intestine in antimicrobially active form. We consider which processes and variables need to be accounted for to project the antimicrobial concentrations in the host's intestine. Those include: the drug's fraction (inclusive of any active metabolites) excreted in bile; the drug's fractions and intestinal segments of excretion via other mechanisms; the rates and intestinal segments of the drug's absorption and re-absorption; the rates and intestinal segments of the drug's abiotic and biotic degradation in the intestine; the digesta passage time through the intestinal segments; the rates, mechanisms, and reversibility of the drug's sorption to the digesta and enteric microbiome; and the volume of luminal contents in the intestinal segments. For certain antimicrobials, the antimicrobial activity can further depend on the aeration and chemical conditions in the intestine. Model forms that incorporate the inter-individual variation in those relevant variables can support projections of the intestinal antimicrobial concentrations in populations of treated host, such as food animals. To illustrate the proposed modeling framework, we develop two examples of treatments of bovine respiratory disease in beef steers by oral chlortetracycline and injectable third-generation cephalosporin ceftiofur. The host's diet influences the digesta passage time, volume, and digesta and microbiome composition, and may influence the antimicrobial loss due to degradation and sorption in the intestine. We consider two diet compositions in the illustrative simulations. The examples highlight the extent of current ignorance and need for empirical data on the variables influencing the selective pressures imposed by antimicrobial treatments on the host's intestinal bacteria.

Topics: Administration, Oral; Animals; Anti-Infective Agents; Bovine Respiratory Disease Complex; Cephalosporins; Chlortetracycline; Gastrointestinal Microbiome; Injections; Male; Models, Biological

Twelve screened cases of bovine respiratory disease (BRD) in calves were enrolled. Six of the calves were treated intramuscularly with sodium ceftiofur (1 mg/kg), and six were treated with nebulised sodium ceftiofur (1 mg/kg). Comparative evaluation of the two therapeutic modalities was based on repetitive analysis of hematological profile of calves on days 0, 5, and 10 post-therapy. The mortality rate in the group of calves treated with the nebulised sodium ceftiofur was significantly (p < 0.001) lower, and their clinical and hematological parameters returned to normal significantly (p < 0.001) faster than in calves treated intramuscularly. Nebulisation of sodium ceftiofur is the most effective treatment in calves with BRD under field conditions. Nasal lavage fluid analysis indicating a high rise of neutrophil count and macrophages may be used as an alternative method to detect pulmonary inflammation in BRD-affected calves.

Topics: Administration, Inhalation; Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cattle Diseases; Cephalosporins; Injections, Intramuscular; Leukocyte Count; Neutrophils; Respiratory Tract Diseases; Treatment Outcome

The purpose of this study was to determine the activities of two antibacterial agents used in the treatment of bovine respiratory infections-tulathromycin, a macrolide, and ceftiofur, a third-generation cephalosporin-alone, in combination with each other, and in combination with each of seven additional antibiotics (tilmicosin, florfenicol, enrofloxacin, danofloxacin, ampicillin, tetracycline, and penicillin G) against bovine Pasteurella multocida (n = 60) and Mannheimia haemolytica (n = 10) isolates for determination of synergy, antagonism, or indifference. Of 458 organism-drug combinations, 160 combinations of tulathromycin and 209 combinations of ceftiofur with eight antimicrobial drugs were indifferent. One combination was antagonistic (ceftiofur + florfenicol against one isolate of P. multocida). Time-kill studies showed loss of cidality for ceftiofur when combined with florfenicol at 1x the minimal inhibitory concentration. Overall, the in vitro data demonstrated that tulathromycin and ceftiofur, in combination with each other or seven other antimicrobial agents, primarily produce an indifferent response with no occurrences of synergism and rare occurrences of antagonism.

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cephalosporins; Disaccharides; Dose-Response Relationship, Drug; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Pasteurella multocida; Time Factors; Treatment Outcome

The relative effect of metaphylactic ceftiofur crystalline free acid (CCFA) versus metaphylactic tilmicosin was evaluated in beef calves under commercial feedlot conditions in Nebraska. At feedlot arrival, 11,605 animals at ultrahigh risk of developing bovine respiratory disease (BRD) were allocated to one of three experimental groups: CCFA-3 (6.6 mg/kg SC), CCFA-7 (6.6 mg/kg), or TILM-3 (tilmicosin, 10 mg/kg SC). Animals were eligible for subsequent BRD treatment 3 (CCFA-3 and TILM-3 groups) or 7 (CCFA-7 group) days later. Compared with the TILM-3 group, overall chronicity, overall mortality, BRD mortality, and metabolic mortality rates were significantly (P < .05) lower in the CCFA-3 and CCFA-7 groups; average daily gain was significantly (P < .05) higher in the CCFA-3 group; the proportion of quality grade No Roll carcasses was significantly (P < .05) lower in the CCFA-3 and CCFA-7 groups; and there were per-animal advantages of 22.05 dollars and 18.98 dollars in the CCFA-3 and CCFA-7 groups, respectively. In beef calves at ultrahigh risk of developing BRD, it is more cost effective to administer metaphylactic CCFA than tilmicosin at feedlot arrival.

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cephalosporins; Dose-Response Relationship, Drug; Injections, Subcutaneous; Macrolides; Male; Random Allocation; Risk Factors; Treatment Outcome; Tylosin