Evaluation of the efficacy of tulathromycin as a metaphylactic antimicrobial in feedlot calves

The purpose of this study was to determine the efficacy and cost-effectiveness of tulathromycin (DRAX) versus tilmicosin (MIC) or oxytetracycline (TET) as a metaphylactic antimicrobial in feedlot calves. Calves that received DRAX had significantly (P<.05) lower initial undifferentiated fever (UF) treatment and relapse rates; lower overall chronicity, overall mortality, and cause-specific mortality rates; higher average daily gains; and improved quality grades. However, calves that received DRAX also had poorer (P<.05) yield grades compared with calves that received MIC or TET and worse feed conversion compared with calves that received MIC. Net advantages in the DRAX group were 3.79CanDollars/animal and 16.96CanDollars/animal compared with the MIC and TET groups, respectively. Based on these results, DRAX is a more efficacious and cost-effective metaphylactic antimicrobial than MIC or TET in feedlot calves at ultra-high risk of developing UF. In addition, this study presents a comparison between two methods ("deads out" and "deads in") of calculating feedlot performance variables.     

Pharmacokinetics of ceftiofur sodium and ceftiofur crystalline free acid in neonatal foals

Ceftiofur, a third generation cephalosporin, demonstrates in vitro efficacy against microorganisms isolated from septicemic neonatal foals. This pharmacokinetic study evaluated the intravenous and subcutaneous administration of ceftiofur sodium (5 mg/kg body weight; n = 6 per group) and subcutaneous administration of ceftiofur crystalline free acid (6.6 mg/kg body weight; n = 6) in healthy foals. Plasma ceftiofur- and desfuroylceftiofur-related metabolite concentrations were measured using high performance liquid chromatography following drug administration. Mean (±SD) noncompartmental pharmacokinetic parameters for i.v. and s.c. ceftiofur sodium were: AUC(0→∝) (86.4 ± 8.5 and 91 ± 22 h·μg/mL for i.v. and s.c., respectively), terminal elimination half-life (5.82 ± 1.00 and 5.55 ± 0.81 h for i.v. and s.c., respectively), C(max(obs)) (13 ± 1.9 μg/mL s.c.), T(max(obs)) (0.75 ± 0.4 h for s.c.). Mean (± SD) noncompartmental pharmacokinetic parameters for s.c. ceftiofur crystalline free acid were: AUC(0→∝) (139.53 ± 22.63 h·μg/mL), terminal elimination half-life (39.7 ± 14.7), C(max(obs)) (2.52 ± 0.35 μg/mL) and t(max(obs)) (11.33 ± 1.63 h). No adverse effects attributed to drug administration were observed in any foal. Ceftiofur- and desfuroylceftiofur-related metabolites reached sufficient plasma concentrations to effectively treat common bacterial pathogens isolated from septicemic foals.     

A comparison of trimethoprim-sulfadoxine and ceftiofur sodium for the treatment of respiratory disease in feedlot calves

A field trial was performed to compare trimethoprim-sulfadoxine to ceftiofur sodium in the treatment of bovine respiratory disease (BRD) in feedlot calves. Five-hundred-and-fifty-five recently weaned, crossbred beef calves, with naturally occurring cases of BRD, were randomly assigned to either trimethoprim-sulfadoxine or ceftiofur sodium treatment groups. The effectiveness of the antibiotics was assessed by comparing relapse rates, three day treatment response rates, mortality rates, chronicity rates, and wastage rates. There was no statistical difference in the first or second relapse rates between the two groups. For the initial therapy, first relapses, and overall treatment episodes, a significantly greater proportion of the calves treated with ceftiofur sodium responded to three days of therapy than those treated with trimethoprim-sulfadoxine (p < 0.05). This resulted in a 10% reduction in treatment costs for calves in the ceftiofur group. There were significantly lower mortality and wastage rates attributable to BRD in the ceftiofur sodium group than in the trimethoprim-sulfadoxine group (p < 0.05). However, there were no significant differences in overall mortality, overall chronicity, or overall wastage rates between the treatment groups.     

Comparative plasma pharmacokinetics of ceftiofur sodium and ceftiofur crystalline‐free acid in neonatal calves

The objective of this study was to compare the plasma pharmacokinetic profile of ceftiofur crystalline‐free acid (CCFA) and ceftiofur sodium in neonatal calves between 4 and 6 days of age. In one group (n = 7), a single dose of CCFA was administered subcutaneously (SQ) at the base of the ear at a dose of 6.6 mg/kg of body weight. In a second group (n = 7), a single dose of ceftiofur sodium was administered SQ in the neck at a dose of 2.2 mg/kg of body weight. Concentrations of desfuroylceftiofur acetamide (DCA) in plasma were determined by HPLC. Median time to maximum DCA concentration was 12 h (range 12–48 h) for CCFA and 1 h (range 1–2 h) for ceftiofur sodium. Median maximum plasma DCA concentration was significantly higher for calves given ceftiofur sodium (5.62 μg/mL; range 4.10–6.91 μg/mL) than for calves given CCFA (3.23 μg/mL; range 2.15–4.13 μg/mL). AUC_0‐∞ and Vd/F were significantly greater for calves given CCFA than for calves given ceftiofur sodium. The median terminal half‐life of DCA in plasma was significantly longer for calves given CCFA (60.6 h; range 43.5–83.4 h) than for calves given ceftiofur sodium (18.1 h; range 16.7–39.7 h). Cl/F was not significantly different between groups. The duration of time median plasma DCA concentrations remained above 2.0 μg/mL was significantly longer in calves that received CCFA (84.6 h; range 48–103 h) as compared to calves that received ceftiofur sodium (21.7 h; range 12.6–33.6 h). Based on the results of this study, CCFA administered SQ at a dose of 6.6 mg/kg in neonatal calves provided plasma concentrations above the therapeutic target of 2 μg/mL for at least 3 days following a single dose. It is important to note that the use of ceftiofur‐containing products is restricted by the FDA and the use of CCFA in veal calves is strictly prohibited.     

Penetration of ceftiofur into sterile vs. Mannheimia haemolytica-infected tissue chambers in beef calves after subcutaneous administration of ceftiofur crystalline free acid sterile suspension in the ear pinna

The effect of Mannheimia haemolytica infection on the penetration of ceftiofur and desfuroylceftiofur metabolites into tissue chambers was studied in cattle after subcutaneous administration of ceftiofur crystalline free acid sterile suspension (CCFA-SS). Four tissue chambers were implanted subcutaneously in each of 12 calves. Approximately 45 days after implantation, two chambers were inoculated with M. haemolytica (10(6) colony-forming units per chamber) while the remaining two chambers were inoculated with sterile phosphate-buffered saline. Twenty-four hours after inoculation, CCFA-SS was administered subcutaneously in the middle third of the caudal ear pinna of each calf. Chamber fluid and blood samples were collected at predetermined times for 10 days following dosing and analyzed for ceftiofur and desfuroylceftiofur metabolites by high-performance liquid chromatography. Concentrations of ceftiofur and desfuroylceftiofur metabolites in plasma and tissue chamber fluid remained above a threshold of 0.2 microg/mL for at least 8 days. Infected tissue chamber fluid concentrations of ceftiofur and desfuroylceftiofur metabolites were significantly higher than those in non-infected tissue chamber fluid, which correlated with significantly higher total protein concentration in infected tissue chambers. These results indicate that single subcutaneous administration of CCFA-SS at 6.6 mg/kg can be expected to provide effective therapy of susceptible bacterial infections for a period of at least 1 week.     

Clinical efficacy of a single injection of ceftiofur crystalline free acid sterile injectable suspension versus three daily injections of ceftiofur sodium sterile powder for the treatment of footrot in feedlot cattle

A study was conducted in a feedlot in Alberta, Canada, to compare the clinical efficacy of a single injection of ceftiofur crystalline free acid sterile injectable suspension with three daily treatments of ceftiofur sodium sterile powder for the treatment of footrot. Use of a long-acting antimicrobial to treat footrot would reduce labor costs and hospital pen space requirements during high-risk periods. Four hundred cattle clinically diagnosed with footrot were systematically randomized to one of two treatment groups. The treatment success rate at 14 days after treatment (99.5% for ceftiofur crystalline free acid sterile injectable suspension and 99.0% for ceftiofur sodium sterile powder for injection) was not statistically different (P>.05) between the two drugs.     

Pharmacokinetics of a long-acting ceftiofur formulation (ceftiofur crystalline free acid) in the ball python (Python regius)

The objective of this study was to determine the pharmacokinetics of a long-acting formulation of ceftiofur crystalline-free acid (CCFA) following intramuscular injection in ball pythons (Python regius). Six adult ball pythons received an injection of CCFA (15 mg/kg) in the epaxial muscles. Blood samples were collected by cardiocentesis immediately prior to and at 0.5, 1, 2, 4, 8, 12, 18, 24, 48, 72, 96, 144, 192, 240, 288, 384, 480, 576, 720, and 864 hr after CCFA administration. Plasma ceftiofur concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was applied to the data. Maximum plasma concentration (Cmax) was 7.096 +/- 1.95 microg/ml and occurred at (Tmax) 2.17 +/- 0.98 hr. The area under the curve (0 to infinity) for ceftiofur was 74.59 +/- 13.05 microg x h/ml and the elimination half-life associated with the terminal slope of the concentration-time curve was 64.31 +/- 14.2 hr. Mean residence time (0 to infinity) was 46.85 +/- 13.53 hr. CCFA at 15 mg/kg was well tolerated in all the pythons. Minimum inhibitory concentration (MIC) data for bacterial isolates from snakes are not well established. For MIC values of < or =0.1 microg/ml, a single dose of CCFA (15 mg/kg) provides adequate plasma concentrations for at least 5 days in the ball python. For MICs > or =0.5 microg/ml, more frequent dosing or a higher dosage may be required.     

Plasma and pulmonary disposition of ceftiofur and its metabolites after intramuscular administration of ceftiofur crystalline free acid in weanling foals

The objectives of this study were to determine the plasma and pulmonary disposition of ceftiofur crystalline free acid (CCFA) in weanling foals and to compare the plasma pharmacokinetic profile of weanling foals to that of adult horses. A single dose of CCFA was administered intramuscularly to six weanling foals and six adult horses at a dose of 6.6 mg/kg of body weight. Concentrations of desfuroylceftiofur acetamide (DCA) were determined in the plasma of all animals, and in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells of foals. After intramuscular (IM) administration to foals, median time to maximum plasma and PELF concentrations was 24 h (12-48 h). Mean (± SD) peak DCA concentration in plasma (1.44 ± 0.46 μg/mL) was significantly higher than that in PELF (0.46 ± 0.03 μg/mL) and BAL cells (0.024 ± 0.011 μg/mL). Time above the therapeutic target of 0.2 μg/mL was significantly longer in plasma (185 ± 20 h) than in PELF (107 ± 31 h). The concentration of DCA in BAL cells did not reach the therapeutic level. Adult horses had significantly lower peak plasma concentrations and area under the curve compared to foals. Based on the results of this study, CCFA administered IM at 6.6 mg/kg in weanling foals provided plasma and PELF concentrations above the therapeutic target of 0.2 μg/mL for at least 4 days and would be expected to be an effective treatment for pneumonia caused by Streptococcus equi subsp. zooepidemicus at doses similar to the adult label.     

Preconditioning calves for the feedlot

Preconditioning is a theoretically sound concept; however, it has not gained wide acceptance by cow-calf producers or feeders owing to logistics and expense. Many of the claims of preconditioning are not substantiated by controlled research data. Many of the positive claims made for preconditioning may be a result of the calves moving more rapidly through the marketing channels. Although preconditioning is profitable to some producers, on the average, preconditioning is difficult to justify economically. Modifications of the preconditioning concept have the potential to make it more feasible to the majority of cow-calf producers. Any producer or feeder considering a preconditioning program or feeding preconditioned calves should first calculate an economic projection.     

An evaluation of the relative efficacy of tulathromycin for the treatment of undifferentiated fever in feedlot calves in Nebraska

A field trial was performed under commercial feedlot conditions in central Nebraska to assess the relative efficacy of tulathromycin (TULA) to florfenicol (FLOR) for the treatment of undifferentiated fever (UF) in feedlot calves that did not receive a metaphylactic antimicrobial or vaccines/bacterins containing Mannheimia haemolytica or Histophilus somni at feedlot arrival by comparing animal health, feedlot performance, and carcass characteristic variables. Two hundred recently weaned, auction market derived, crossbred beef calves that met the study-specific case definition of UF were randomly allocated in a 1:1 ratio to 1 of 2 experimental groups as follows: TULA, which received tulathromycin administered subcutaneously at the rate of 2.5 mg/kg body weight (BW) once at the time of allocation; or FLOR, which received florfenicol administered subcutaneously at the rate of 40 mg/kg BW once at the time of allocation. In terms of animal health, the first UF relapse (RR = 0.65), overall mortality (RR = 0.33), and BRD mortality (RR = 0.29) rates in the TULA group were significantly (P < 0.05) lower than in the FLOR group. There were no significant (P > or = 0.05) differences between the TULA and FLOR groups for the other animal health variables measured. There was no significant (P > or = 0.05) difference in average daily gain between the TULA and FLOR groups. There were no significant (P > or = 0.05) differences in the overall distributions of quality grade and yield grade between the experimental groups; however, a significantly (P < 0.05) higher proportion of carcasses in the TULA group graded yield grade USDA-4 as compared with the FLOR group. In the economic analysis, the benefits observed resulted in an economic advantage of $52.50 USD/animal in the TULA group due to lower first UF relapse and overall mortality rates, even though the occurrence of yield grade USDA-4 carcasses increased and the initial UF treatment cost was higher.     

An economic evaluation of metabolic and cellular profile testing in calves to be raised in a feedlot

The economic value of the metabolic and cellular profile test as a predictor of feedlot calves' performance was determined. The economic technique used in this evaluation was decision tree analysis. Results showed that in a case study evaluation such as this one, the metabolic and cellular profile test would not be recommended. Further, under the assumptions used, even if the test were perfected, the cost of the test should not exceed $2.79. The application of decision tree analysis demonstrated how questions concerning the economics of animal health issues may be formulated and solved.     

Phosphorus requirement of finishing feedlot calves

Dietary P supplied to feedlot cattle is important because an inadequate supply will compromise performance, whereas excess P may harm the environment. However, P requirements of feedlot cattle are not well documented. Therefore, 45 steer calves (265.2+/-16.6 kg) were individually fed to determine the P required for gain and bone integrity over a 204-d finishing period. The basal diet consisted of 33.5% high-moisture corn, 30% brewers grits, 20% corn bran, 7.5% cottonseed hulls, 3% tallow, and 6% supplement. Treatments consisted of 0.16 (no supplemental inorganic P), 0.22, 0.28, 0.34, and 0.40% P (DM basis). Supplemental P was provided by monosodium phosphate top-dressed to the daily feed allotment. Blood was sampled every 56 d to assess P status. At slaughter, phalanx and metacarpal bones were collected from the front leg to determine bone ash and assess P resorption from bone. Dry matter intake and ADG did not change linearly (P > 0.86) or quadratically (P > 0.28) due to P treatment. Feed efficiency was not influenced (P > 0.30) by P treatment and averaged 0.169. Plasma inorganic P averaged across d 56 to 204 responded quadratically, with calves fed 0.16% P having the lowest concentration of plasma inorganic P. However, plasma inorganic P concentration (5.7 mg/dL) for steers fed 0.16% P is generally considered adequate. Total bone ash weight was not influenced by dietary P for phalanx (P = 0.19) or metacarpal bones (P = 0.37). Total P intake ranged from 14.2 to 35.5 g/d. The NRC (1996) recommendation for these calves was 18.7 g/d, assuming 68% absorption. Based on performance results, P requirements for finishing calves is < 0.16% of diet DM or 14.2 g/d. Based on these observations, we suggest that typical grain-based feedlot cattle diets do not require supplementation of inorganic mineral P to meet P requirements.     

Dose determination and confirmation of a long-acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease

The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil(R) 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1-8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4-8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4-5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4-5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time.     

Distribution of ceftiofur into Mannheimia haemolytica‐infected tissue chambers and lung after subcutaneous administration of ceftiofur crystalline free acid sterile suspension

Washburn, K., Johnson, R., Clarke, C, Anderson, K. Distribution of ceftiofur into Mannheimia haemolytica‐infected tissue chambers and lung after subcutaneous administration of ceftiofur crystalline free acid sterile suspension. J. vet. Pharmacol. Therap. 33 , 141–146. The objective of this study was to evaluate the penetration of ceftiofur‐ and desfuroylceftiofur‐related metabolites (DCA) into sterile and infected tissue chambers, lung tissue and disposition of DCA in plasma across four different sacrifice days postdosing. Twelve healthy calves were utilized following implantation with tissue chambers in the paralumbar fossa. Tissue chambers in each calf were randomly inoculated with either Mannheimia haemolytica or sterile PBS. All calves were dosed with ceftiofur crystalline free acid sterile suspension (CCFA‐SS) subcutaneously in the ear pinna. Calves were randomly assigned to 4 groups of 3 to be sacrificed on days 3, 5, 7 and 9 postdosing. Prior to euthanasia, plasma and tissue chamber fluid were collected, and immediately following euthanasia, lung tissue samples were obtained from four different anatomical sites DCA concentration analysis. Results of our study found that, in general, DCA concentrations followed a rank order of plasma > infected tissue chamber fluid > noninfected tissue chamber fluid > lung tissue. Data also indicated DCA concentrations remained above the therapeutic threshold of 0.2 μg/mL for plasma and chamber fluid and 0.2 μg/g for lung tissue for at least 7 days post‐treatment.     

Preparing Holstein steer calves for the feedlot.

It is increasingly common to raise Holstein steer calves for entry to feedlot production systems rather than more traditional milk-fed veal production systems. Providing adequate nutritional support for the maintenance and growth of Holstein calves is essential in preparing them for a commercial feedlot environment. In this article, the dietary requirements of preruminant calves are reviewed and examples of evaluating milk diets for Holstein calves are detailed. The importance of the transition between milk feeding and grain-forage diets is discussed. Aspects of disease prevention, such as coccidiosis control and colostrum feeding, are also discussed. The reader will gain practical tools to use in preventive medicine programs involving Holstein steers being prepared for commercial feedlots.     

B-vitamin supplementation of diets for feedlot calves

B-vitamin supplementation of diets for 144 shipping-stressed crossbred calves (116 kg) at levels up to 10 times that recommended for growing pigs did not influence (P greater than .20) weight gain or feed conversion during a 56-d receiving trial. However, vitamin supplementation tended (P less than .10) to reduce morbidity. In a second trial, supplemental B-vitamins had no effect (P greater than .20) on efficiency of microbial growth or site and extent of digestion of organic matter, acid detergent fiber and N. Supplemental dietary riboflavin, niacin, folic acid, B12 and ascorbic acid were largely metabolized [degraded and (or) absorbed] anterior to the small intestine, with escape values of 1, 3, 10 and 0% of added vitamins, respectively, while dietary B6 and biotin largely escaped the rumen. Thiamine and pantothenic acid were intermediate in ruminal escape (52 and 22%, respectively). Small intestinal absorption of thiamine, niacin, riboflavin, B6 and B12 averaged 75, 79, 25, 79 and 48%, respectively. Coefficients for ruminal escape and microbial synthesis for each B-vitamin were calculated using the slope-ratio technique. Measured flows for thiamine, riboflavin and B12 in a third experiment were similar to flows predicted from escape and synthesis equations, though flow of niacin and B6 were under-predicted by 37 and 44%, respectively. Results are interpreted to indicate that intestinal B-vitamin supply can be predicted based on dietary composition and intake.     

Prophylactic medication of feedlot calves with tilmicosin

The parenteral administration to calves of the antibiotic tilmicosin either on arrival at a feedlot or 72 hours later was evaluated in a group of 308 steer calves. The calves were allotted to 24 pens so that there were eight replicates of the two medicated groups and eight replicates of the control group. The need for veterinary treatment was reduced significantly (P less than 0.05) during the first month of the feeding period in the two medicated groups. The medicated groups had an improved average daily weight gain (P less than 0.01) over the trial period compared with the non-medicated animals. This improved average daily gain by the medicated groups was not reduced when animals with respiratory disease were excluded from the calculations. The medicated groups also had an improved feed conversion efficiency (P less than 0.01) over the first 60 days of the feeding period compared with the non-medicated animals.