A comparison of prophylactic efficacy of tilmicosin and a new formulation of oxytetracycline in feedlot calves

Abstract

Two replicated-pen field studies were performed under commercial feedlot conditions in western Canada to compare the administration of long-acting oxytetracycline at 30 mg/kg body weight (BW) versus tilmicosin at 10 mg/kg BW to feedlot calves upon arrival at the feedlot. Ten thousand nine hundred and eighty-nine, recently weaned, auction market derived, crossbred beef steer and bull calves were randomly allocated upon arrival at the feedlot to one of 2 experimental groups as follows: oxytetracycline, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at a rate of 30 mg/kg BW; or tilmicosin, which received subcutaneous tilmicosin (300 mg/mL formulation) at a rate of 10 mg/kg BW. There were 20 pens in each experimental group. In Study 1 and in the combined analysis, the initial undifferentiated fever (UF) treatment rate was significantly (P < 0.05) higher in the oxytetracycline group as compared with the tilmicosin group. There were no significant (P ≥ 0.05) differences in first UF relapse, second UF relapse, third UF relapse, overall chronicity, overall rail, overall mortality, bovine respiratory disease (BRD) mortality, hemophilosis mortality, arthritis mortality, or miscellaneous mortality rates between the experimental groups in either study or in the combined analysis. In addition, there were no significant (P ≥ 0.05) differences in initial weight, final weight, weight gain, days on feed, daily dry matter intake, average daily gain, or the dry matter intake to gain ratio between the experimental groups in either study or in the combined analyses. In the economic analysis, there was a net economic advantage of $5.22 CDN per animal in the oxytetracycline group, due to a lower prophylactic cost, even though the UF therapeutic cost was higher.

Introduction

In beef feedlot production, undifferentiated fever (UF), also referred to as bovine respiratory disease (BRD) complex or shipping fever, is the single most important health problem (1,2,3,4,5,6,7,8). The management of this disease complex has become significantly more sophisticated with the administration of prophylactic or metaphylactic antimicrobials to calves upon arrival at the feedlot (9,10,11,12,13,14,15,16,17,18,19,20). Studies utilizing prophylactic parenteral oxytetracycline or tilmicosin in feedlot cattle have demonstrated reductions in BRD morbidity rates, BRD mortality rates, and, or, overall mortality rates and improvements in average daily gain and, or, feed efficiency, as compared with no prophylaxis (9,10,11,12,13,15,16,17,18,19). However, comparisons between oxytetracycline and tilmicosin programs have shown that prophylactic tilmicosin programs result in lower BRD morbidity rates, BRD mortality rates, and, or, overall mortality rates and improved average daily gain and, or, feed efficiency (19,20).

In the aforementioned studies (19,20), the concentration of the oxytetracycline formulations used was 200 mg/mL and the dosage administered was 20 mg/kg body weight (BW) given once on arrival at the feedlot (19) or once on arrival at the feedlot and again 3 d later (20). A more concentrated oxytetracycline formulation (Tetradure LA-300; Merial Canada, Baie d'Urfé, Quebec) has been developed. The relative prophylactic efficacy of this 300 mg/mL oxytetracycline formulation administered at a dose of 30 mg/kg BW is unknown. As a result, the purpose of the study reported herein was to compare the administration of IM long-acting oxytetracycline (Tetradure LA-300) at 30 mg/kg BW versus SC tilmicosin (Micotil; Provel, Division of Eli Lilly Canada, Guelph, Ontario) at 10 mg/kg BW to calves upon arrival at the feedlot.

Materials and methods

Study facilities

Study 1 was conducted at a commercial feedlot with a capacity of 24 000 animals located near Strathmore, Alberta. Study 2 was conducted at a commercial feedlot with a capacity of 25 000 animals located near Vegreville, Alberta. The basic design of each feedlot is representative of standard designs used in western Canada. Animals are housed in open-air, dirt-floor pens arranged side by side with central feed alleys and 20% porosity wood-fence windbreaks. There are 80 to 90 large pens at each feedlot that each house approximately 300 animals. There are 2 hospital facilities and an enclosed processing facility located at each feedlot. Each hospital facility has a hydraulic chute equipped with an individual animal scale, a chute-side computer for the collection of animal health data, and separation alleys to facilitate the return of cattle to designated feedlot pens. Several open-air hospital pens are located adjacent to each hospital. In addition, the processing facility at each feedlot has a hydraulic chute equipped with an individual animal scale and several adjacently located receiving pens.

Study animals

The animals utilized in this study were recently weaned crossbred beef steer and bull calves purchased from auction markets throughout western Canada. Each study was conducted over 2 y. Seven replicates were allocated to Study 1 in the fall of 1995 and 3 replicates were allocated to Study 1 in the fall of 1996. Three replicates were allocated to Study 2 in the fall of 1996 and 7 replicates were allocated to Study 2 in the fall of 1997. The animals allocated to the study were approximately 7 to 10 mo of age. The average individual animal weight of each pen allocated to Study 1 was between 228 kg and 338 kg. The average individual animal weight of each pen allocated to Study 2 was between 269 kg and 283 kg.

Upon arrival at the feedlot, all animals were moved through a hydraulic chute for a group of procedures known collectively as processing, which included weighing, ear tagging to provide unique, individual animal identification, and castration of all bulls.

In Study 1, all animals were vaccinated against infectious bovine rhinotracheitis (IBR) and parainfluenza-3 (PI₃) viruses (IBR-PI₃ 48; Boehringer Ingelheim Vetmedica, Burlington, Ontario), administered a multivalent clostridial and Haemophilus somnus vaccine (Fermicon 7-Somnugen, Boehringer Ingelheim Vetmedica), and given an injection of vitamins A and D (Poten AD; Animal Health Group, Pfizer Canada, London, Ontario) at processing. In addition, all animals received a Mannheimia (formerly Pasteurella) haemolytica bacterin/toxoid (One Shot; Animal Health Group, Pfizer Canada) and topical ivermectin (Ivomec Pour-On for Cattle; Merial Canada) at 1.0 mL/10 kg BW. In year 1 of Study 1, all animals received a progesterone/estradiol combination implant (Synovex S; Ayerst Veterinary Laboratories, Division of Wyeth-Ayerst Canada, Guelph, Ontario) and, in year 2 of Study 1, all animals received a zeranol implant (Ralgro; Schering-Plough Animal Health, Division of Schering Canada, Pointe-Claire, Quebec) at processing.

In Study 2, all animals were vaccinated against IBR, PI₃, and bovine viral diarrhea (BVD) viruses (Bovishield 3; Animal Health Group, Pfizer Canada) and administered a multivalent clostridial and Haemophilus somnus vaccine (Ultrabac 7/Somubac; Animal Health Group, Pfizer Canada) at processing. In addition, all animals received an autogenous Mycoplasma spp. bacterin (Microbix Biosystems, Toronto, Ontario), a Mannheimia haemolytica bacterin/toxoid (One Shot), topical ivermectin (Ivomec Pour-On for Cattle) at 1.0 mL/10 kg BW, and a zeranol implant (Ralgro) at processing.

In year 1 of Study 1, animals were implanted with a progesterone/estradiol combination implant (Synovex S) and vaccinated against IBR and PI₃ viruses (IBR-PI₃ 48) at approximately 90 d on feed for each pen. In year 2 of Study 1, animals were implanted with an estradiol/ trenbolone acetate combination implant (Synovex Plus; Ayerst Veterinary Laboratories, Division of Wyeth-Ayerst Canada) and vaccinated against IBR and PI₃ viruses (IBR-PI₃ 48) at approximately 70 d on feed for each pen. In Study 2, all animals were implanted with an estradiol/ trenbolone acetate combination implant (Synovex Plus or Revalor-S; Hoechst Roussel Vet, Regina, Saskatchewan) and vaccinated against IBR and PI₃ viruses (Bovishield IBR-PI₃; Animal Health Group, Pfizer Canada) at approximately 70 d on feed for each pen. Note that within a replicate, the same products (excluding the prophylactic antimicrobial) were administered to both experimental groups.

Experimental design

Using variance estimates for average daily gain (ADG) and the dry matter intake to gain ratio (DM:G) from studies previously conducted at each feedlot (Jim, Guichon, Booker, Schunicht, Wildman, and Hill, unpublished observations), it was calculated for each study that approximately 10 pens per experimental group would be required to have a 90% chance of detecting differences in ADG or DM:G of 2% to 3% or larger (β = 0.10), and to be 95% confident that these differences were not due to chance (α = 0.05).

Upon arrival at each feedlot, individual animals from each processing group were randomly assigned to one of 2 experimental groups as follows by using a computer-generated randomization table: oxytetracycline, which received IM long-acting oxytetracycline (300 mg/mL formulation) at the rate of 30 mg/kg BW; or tilmicosin, which received SC tilmicosin (300 mg/mL formulation) at the rate of 10 mg/kg BW. Animals in each experimental group were assembled in a designated pen until that pen contained up to 320 animals. Replicates (1 pen from each experimental group) were filled consecutively. In total, 5495 animals were allocated to the oxytetracycline group and 5494 animals were allocated to the tilmicosin group.

Feeding program

Standard mixed complete feedlot diets, formulated to meet or exceed the nutritional requirements of feedlot cattle, were offered ad libitum (21,22). The experimental diets were blended by combining rolled barley, barley silage, and supplement in truck-mounted mixer boxes (Harshmixer, Hydraulics Unlimited, Eaton, Colorado, USA) equipped with electronic load cells. The supplements were manufactured in a granular form by a commercial feed mill (Landmark Feeds, Strathmore, Alberta). The diets were weighed and delivered to the pens once or twice daily. Water was provided ad libitum. The animals were adapted to finisher diets over a 50-day period by increasing the proportion of rolled barley and decreasing the proportion of barley silage at approximately 7-day intervals.

Silage was sampled weekly and the dry matter content was determined. From these data, the weekly average dry matter content of the diets was calculated and used to calculate the weekly dry matter intake for each pen.

Animal health

The animals were observed once or twice daily by experienced animal health personnel. The animal health personnel were blinded as to the experimental status of each pen. Animals deemed to be “sick” by the animal health personnel were moved to the hospital facility, diagnosed, and treated as per the written treatment protocols provided by the consulting veterinarians. In these studies, the case definition for UF was a lack of abnormal clinical signs referable to body systems other than the respiratory system and an elevated rectal temperature (≥ 40.3°C). All animal health events, including treatment date, presumptive diagnosis, drug(s) used, and dose(s) administered, were recorded on the chute-side computer system.

In Study 1, all animals that died were necropsied by the attending study veterinarian and the cause of death was determined, based on the findings of the gross postmortem examination. In Study 2, trained feedlot personnel prosected all animals that died, by using a standardized method, and captured the appropriate digital images, as outlined in the written necropsy protocol provided by the study veterinarians. Subsequently, these images were electronically transferred to the study veterinarians, so that the cause of death could be determined for each animal, based on the findings of the gross postmortem examination (23).

Marketing

The animals were sold under normal marketing procedures, whereby the feedlot manager, based on visual appraisal, determined that a specific number of loads were ready for sale in each pen. When animals were sold, approximately the same number of animals was shipped from each experimental group within a replicate to the same packing plant on the same day. In Study 1, the animals were sold on a carcass-price basis and, in Study 2, the animals were sold on a live-price basis. Prior to shipment for slaughter, all animals fulfilled the withdrawal times established by the Bureau of Veterinary Drugs for all products used in the study.

Data collection and management

Each animal was weighed at processing and the weight was recorded. In addition, all animals that died or were slaughtered for salvage purposes (rail) were individually weighed and the weight recorded on the day that the event occurred. In Study 1, the hot weight of each carcass was measured and recorded at slaughter. In Study 2, animals were group weighed on the day of slaughter.

In both studies, the computerized animal health data were verified and summarized. From these data, initial UF treatment, first UF relapse, second UF relapse, third UF relapse, overall chronicity (animals designated as “chronic” by animal health personnel and kept in the hospital facility for convalescence), overall rail, overall mortality, BRD mortality (bronchopneumonia, bronchointerstitial pneumonia, chronic pneumonia, chronic pleuritis, fibrinous pneumonia, lung abscess, or pneumonia and arthritis), hemophilosis mortality (laryngitis, myocarditis, pericarditis, pleuritis, septicemia, or thromboembolic meningoencephalitis), metabolic mortality (atypical interstitial pneumonia, bloat, or caudal vena caval thrombosis), arthritis mortality, and miscellaneous mortality (abscess/cellulitis, aspiration pneumonia, BVD/mucosal disease, chronic bloat, coccidiosis, embolic pneumonia, enteritis, gangrenous necrosis of the extremities, intestinal torsion, laryngeal and tracheal edema, musculoskeletal injury, nervous disease, neoplasia, peritonitis, pyelonephritis, ruptured aortic aneurysm, urolithiasis, or no gross lesions/unknown) rates were calculated (Table 1). The variables measured to assess feedlot performance were initial weight, final weight, weight gain, days on feed (DOF), daily dry matter intake (DDMI), ADG, and DM:G.

Table 1.

In Study 1, the Canadian quality grade (CQG) and Canadian yield grade (CYG) of each carcass were collected at slaughter. With respect to CQG, the proportions of animals in each pen grading Canada Prime or Canada AAA, Canada AA, Canada A, B1, B2, B3, B4, or E were calculated for each pen. With respect to CYG, the proportions of Canada AAA, Canada AA, and Canada A carcasses within each pen that graded Canada 1, Canada 2, or Canada 3 were calculated (Table 5).

Table 5.

Statistical analysis

The data were analyzed by using an analytical software program (SAS System for Windows, v. 6.12; SAS Institute Inc., Cary, North Carolina, USA). The animal health variables were compared between the experimental groups by using linear logistic regression modeling techniques controlling for within-pen clustering of disease by using the method previously described (24) and reviewed (25,26). The feedlot performance and carcass grading variables were compared between the experimental groups by using least squares analysis of variance for replicate and experimental group effects (27).

Economic analysis

The relative cost-effectiveness of the experimental groups was calculated by using a proprietary computer spreadsheet program (Microsoft Excel 97; Microsoft Corporation, Redmond, Washington, USA) that simulates all economic aspects of feedlot production, as previously described (4,28). In the economic model, the initial weight, final weight, ADG, DM:G, feeder price, slaughter price, ration cost, processing cost, yardage rate, interest rate, first UF relapse rate, second UF relapse rate, third UF relapse rate, overall chronicity rate, overall rail rate, and overall mortality rate were fixed for both experimental groups. The costs of the prophylactic programs used in the economic analysis for the oxytetracycline and tilmicosin groups were $5.00 CDN and $11.00 CDN per animal, respectively. The cost of initial UF treatment, first UF relapse treatment, second UF relapse treatment, and third UF relapse treatment were $21.00 CDN, $6.00 CDN, $12.00 CDN, and $18.00 CDN, respectively. The interest rate used in the analysis was 7.5% per annum. The actual initial UF treatment rate of each experimental group from the combined studies was used in the economic analysis.

Results

The morbidity and mortality variables for both studies are presented in Tables 2 and 3, respectively. In Study 1 and in the combined analysis, the initial UF treatment rate was significantly (P < 0.05) higher in the oxytetracycline group as compared with the tilmicosin group. There were no significant (P ≥ 0.05) differences in first UF relapse, second UF relapse, third UF relapse, overall chronicity, overall rail, overall mortality, BRD mortality, hemophilosis mortality, arthritis mortality, or miscellaneous mortality rates between the experimental groups in either study or in the combined analyses.

Table 2.

Table 3.

The feedlot performance variables for both studies are presented in Table 4. There were no significant (P ≥ 0.05) differences in initial weight, final weight, weight gain, DOF, DDMI, ADG, or the DM:G between the experimental groups in either study or in the combined analysis.

Table 4.

In the economic analysis, there was a net advantage of $5.22 CDN per animal in the oxytetracycline group as compared with the tilmicosin group.

Discussion

The results of this study demonstrate that the prophylactic use of long-acting oxytetracycline in recently weaned, auction market derived, feedlot calves is comparable with that of tilmicosin with respect to mortality and feedlot performance but is associated with a higher initial UF treatment rate. The higher UF treatment rate in the oxytetracycline group is consistent with the findings of previous studies, whereas the comparable mortality and feedlot performance observed in this study are in contrast to previous studies, where prophylactic tilmicosin resulted in lower BRD mortality rates, lower overall mortality rates, improved ADG, and, or, improved feed efficiency as compared with oxytetracycline (19,20). The formulation and dosage of oxytetracycline used in the current study (300 mg/mL administered at 30 mg/kg BW) are different from the formulation and dosage evaluated in previous studies (200 mg/mL administered at 20 mg/kg BW), and this may account for the differences observed between the earlier studies and the present one. However, it cannot be determined from the results of this study if the improved prophylactic efficacy of oxytetracycline is due to the different formulation, higher dosage, a combination of both formulation and dosage, or other factors.

In the economic analysis, the initial UF treatment rate was the only outcome variable that was incorporated in the model, because this was the only variable that was significantly (P < 0.05) different between the experimental groups. The economic advantage in the oxytetracycline group was due to a $6.00 CDN per animal lower prophylactic antimicrobial cost, a $0.10 CDN per animal lower interest cost, and a $0.88 CDN per animal higher therapeutic cost. The difference in initial UF treatment rates between the oxytetracycline and tilmicosin groups was wider in Study 1 than in Study 2. If the difference in initial UF treatment rates from Study 1 was used, the economic advantage in the oxytetracycline group would decrease to $4.83 CDN per animal. Conversely, if there was no difference (P ≥ 0.05) in initial UF treatment rates between the experimental groups, as observed in Study 2, the economic advantage in oxytetracycline group would increase to $6.12.

In summary, the results of this study demonstrate that, in recently weaned, auction market derived steer and bull calves entering feedlots in western Canada in the fall of the year, the prophylactic use of long-acting oxytetracycline (300 mg/mL formulation) administered at a dose of 30 mg/kg BW is more cost-effective than tilmicosin (300 mg/mL formulation) administered at a dose of 10 mg/kg BW, owing to a lower cost of prophylaxis, despite significantly higher UF therapeutic costs.