tilmicosin and tulathromycin

The objective of this project was to evaluate the effects of antimicrobials approved for parenteral metaphylactic use in feeder and stocker calves on morbidity and mortality for bovine respiratory disease with the use of a mixed treatment comparison meta-analysis. An initial literature review was conducted in April 2016 through Pubmed, Agricola, and CAB (Commonwealth Agricultural Bureau) for randomized controlled trials for metaphylaxis antimicrobial administered parentally to incoming feedlot or stocker calves within 48 h of arrival. The final list of publications included 29 studies, with a total of 37 trials. There were 8 different metaphylactic antimicrobials. Final event outcomes were categorized into bovine respiratory disease (BRD) morbidity cumulative incidence d 1 to ≤ 60 of the feeding period, BRD morbidity cumulative incidence d 1 to closeout of the feeding period, BRD mortality cumulative incidence d 1 to closeout of the feeding period, and BRD retreatment cumulative incidence morbidity d 1 to closeout of the feeding period. Network meta-analysis combined direct and indirect evidence for all the event outcomes to determine mean odds ratio (OR) with 95% credibility intervals (CrIs) for all metaphylactic antimicrobial comparisons. The "upper tier" treatment arms for morbidity d 1 to ≤ 60 included tulathromycin, gamithromycin, and tilmicosin. For BRD mortality cumulative incidence d 1 to closeout and BRD retreatment morbidity d 1 to closeout, classifying the treatment arms into tiers was not possible due to overlapping 95% CrIs. The results of this project accurately identified differences between metaphylactic antimicrobials, and metaphylactic antimicrobial options appear to offer different outcomes on BRD morbidity and mortality odds in feedlot cattle.

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Disaccharides; Heterocyclic Compounds; Incidence; Macrolides; Tylosin

The objectives of this study were to 1) quantify effects of metaphylactic treatment for bovine respiratory disease (BRD) on growth performance, carcass characteristics, and lung lesion prevalence and severity; 2) evaluate the association of lung lesion prevalence and severity with carcass characteristics; and 3) evaluate effects of therapeutic treatment on carcass characteristics and lung lesion prevalence and severity. The study was conducted at a commercial feedlot in the Texas Panhandle in which steers (n = 2,336) initially weighing 312.1 ± 9.6 kg were sourced from auction markets and allocated in a randomized complete block design to 1 of 3 treatments (no metaphylactic [no antimicrobial drug {ND}] treatment, tilmicosin at 10 mg/kg BW [TIL], and tulathromycin at 2.5 mg/kg BW [TUL]). Lungs of all steers were evaluated during harvest to assess presence and severity of pneumonic lesions in the anteroventral lobes and the presence and severity of pleural adherences. Compared to the ND treatment, steers treated via metaphylactic therapy had greater (P < 0.05) metaphylactic cost, ADG, shrunk final BW, dressed carcass yield, HCW, 12th rib fat, calculated empty body fat (EBF), and gross revenue, concurrent with reduced (P < 0.05) BRD treatment costs and financial losses from BRD death and railed cattle, cumulatively resulting in greater financial returns. Lung lesions were present in 64.3% of lungs and were distributed similarly between metaphylactic treatments (63.9%) and ND (65.1%) cattle. Steers with advanced lung lesions present at harvest were associated with reduced (P < 0.05) HCW, KPH, 12th rib fat, calculated yield grades, marbling scores, and calculated EBF as compared to steers without lung lesions. Steers pulled for BRD had increased (P < 0.01) incidence of advanced lung lesions, mortality, and railers with decreased (P < 0.05) HCW, 12th rib fat, KPH, marbling score, calculated EBF, and percentage choice carcasses when compared to non-BRD event steers. From the results of this study, controlling BRD through the use of metaphylactic treatments on arrival in heavier cattle improved financial returns primarily driven by reductions in cost of death loss and railers.

Topics: Adipose Tissue; Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Body Composition; Bovine Respiratory Disease Complex; Cattle; Cost-Benefit Analysis; Disaccharides; Heterocyclic Compounds; Lung; Male; Prevalence; Random Allocation; Severity of Illness Index; Texas; Treatment Outcome; Tylosin

Health and feed performance parameters of 293 beef stocker calves at risk for bovine respiratory disease were compared after metaphylactic administration of one of two antimicrobials (tulathromycin or tilmicosin) with different durations of activity; the antimicrobial was administered 1 day after arrival. Calves that received metaphylactic tulathromycin displayed significant improvement in morbidity, mortality, and first-treatment success rates (P<.05) compared with tilmicosin-treated calves. Tulathromycin-treated calves also showed a significantly improved average daily gain and feed:gain ratio (P<.05) compared with tilmicosin-treated calves. Under conditions of this study, calves receiving tulathromycin were healthier through a 43-day growing phase compared with calves receiving tilmicosin. This health difference likely accounted for the differences in feed performance between the treatment groups.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Eating; Health Status; Heterocyclic Compounds; Male; Treatment Outcome; Tylosin; Weight Gain

The efficacy of tulathromycin in the treatment (phase 1) and prevention (phase 2) of bovine respiratory disease (BRD) was evaluated on commercial farms in France, Germany, Italy, and Spain. In phase 1, commingled cattle with clinical BRD were treated with tulathromycin (n = 128) or florfenicol (n = 125) on day 0. Similar percentages of animals showed sustained clinical improvement at day 14 (tulathromycin 83.3% versus florfenicol 81.0%) and had not relapsed by day 60 (tulathromycin 63.3% versus florfenicol 58.4%). In phase 2, healthy in-contact cattle were treated with tulathromycin (n = 492), tilmicosin (n = 494), or saline (n = 265) on day 0. Significantly more (P = .0001) tulathromycin-treated cattle remained healthy to day 14 (92.4%) than tilmicosin-treated (83.7%) or saline-treated (63.7%) cattle, and this was maintained through day 60 (tulathromycin 85.4% versus tilmicosin 75.1% and saline 56.2%). Tulathromycin was highly effective in the treatment and prevention of BRD.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Disease Outbreaks; Europe; Haemophilus somnus; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Mannheimia haemolytica; Mycoplasma bovis; Pasteurella multocida; Pasteurellosis, Pneumonic; Thiamphenicol; Tylosin

Efficacy and field safety of tulathromycin administered as a single-dose treatment to crossbreed beef calves with undifferentiated bovine respiratory disease (BRD) were evaluated in a multicenter field study conducted at four US feedlots. Two hundred castrated male calves were enrolled at each study site. The treatment groups were physiologic saline (n = 160) given SC at 0.02 ml/kg, tulathromycin (n = 320) given SC at 2.5 mg/kg, and tilmicosin (n = 320) given SC at 10 mg/kg. Nasopharyngeal swabs for bacterial culture were obtained before treatment. The cure rate for calves treated with tulathromycin (78%) and tilmicosin (65%) was significantly (P < or = .0001) higher than that of calves treated with saline (23.8%). The cure rate of calves treated with tulathromycin (78.4%) was significantly (P = .0007) higher than that of calves treated with tilmicosin (64.9%). No adverse events related to tulathromycin were reported. Under the conditions of this study, tulathromycin administered as a single-dose treatment was efficacious in the treatment of undifferentiated BRD.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Male; Nasopharynx; Pasteurellosis, Pneumonic; Treatment Outcome; Tylosin; United States

Three studies conducted at feedlots in Colorado, Idaho, and Texas examined the comparative efficacy of tulathromycin injectable solution for the treatment of cattle at high risk of developing undifferentiated bovine respiratory disease (BRD). Each study randomly allocated 250 calves to receive tulathromycin at 2.5 mg/kg and 250 calves to receive either tilmicosin at 10 mg/kg (Colorado site) or florfenicol at 40 mg/kg (Idaho and Texas sites) on arrival at the feedlot. Calves were housed by treatment group in pens with 50 calves/pen. Beginning 3 days after antimicrobial treatment, cattle were observed for signs of BRD daily until harvest. In all three studies, the treatment success rates at 28 days after treatment and at harvest were significantly higher (P < or = .013) for cattle treated with tulathromycin than for cattle treated with either tilmicosin or florfenicol. Fewer tulathromycin-treated cattle were removed from the group as "chronics" or "mortalities" at 28 days posttreatment (P < or = .014) in all three studies. Tulathromycin demonstrated superior efficacy compared with tilmicosin and florfenicol when treating groups of high-risk cattle before the onset of signs of BRD.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Male; Pasteurellosis, Pneumonic; Recurrence; Risk Factors; Severity of Illness Index; Thiamphenicol; Treatment Outcome; Tylosin; United States

The efficacy of tulathromycin in decreasing the incidence of morbidity and mortality due to bovine respiratory disease (BRD) in 1,239 high-risk cattle was investigated at four US feedlots. Calves not exhibiting clinical signs of BRD received one of three treatments administered subcutaneously in the neck: physiologic saline at 0.02 ml/kg, tulathromycin at 2.5 mg/kg, or tilmicosin at 10 mg/kg. Each treatment group consisted of 413 calves. Calves with clinical signs of BRD and rectal temperatures of 104 degrees F or higher on days 1 through 14 were considered treatment failures (BRD morbidity). Nasopharyngeal swabs from saline-treated morbidities were submitted for isolation and identification of BRD organisms. Respiratory disease morbidity was highest in calves treated with saline and significantly (P < or = .0001) lower in calves administered tulathromycin or tilmicosin. Morbidity from BRD was significantly (P < or = .0001) higher in calves treated with tilmicosin than in calves treated with tulathromycin. Under conditions of this study, tulathromycin, given to calves at high risk of developing BRD, was significantly more effective in reducing BRD morbidity when compared to both saline- and tilmicosin-treated calves.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Male; Nasopharynx; Pasteurellosis, Pneumonic; Risk Factors; Treatment Outcome; Tylosin

The therapeutic efficacy and field safety of tulathromycin were evaluated in stocker calves with undifferentiated bovine respiratory disease (BRD) in three field studies conducted over two consecutive grazing seasons in Nebraska. Eight hundred calves exhibiting clinical signs of BRD and with rectal temperatures of 104 degrees F or higher were treated with tulathromycin (n = 340), florfenicol (n = 240), or tilmicosin (n = 220) and evaluated for approximately 60 days. Florfenicol and tilmicosin were administered as single SC injections according to labeled dosage. Tulathromycin was administered as a single SC injection of 2.5 mg/kg. In all three studies, the cure rate of calves 60 days after treatment with tulathromycin was significantly higher (P < or = .05) than that of calves treated with florfenicol or tilmicosin. Suspected adverse reactions were not reported for any of the study drugs. Tulathromycin proved to be significantly more effective than either florfenicol or tilmicosin in the treatment of BRD in stocker calves.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Male; Pasteurellosis, Pneumonic; Recurrence; Severity of Illness Index; Thiamphenicol; Treatment Outcome; Tylosin; United States; Weight Gain

Four studies conducted at feedlots in Greeley and Wellington, Colorado; Nebraska; and Texas compared the efficacy of tulathromycin to florfenicol or tilmicosin for the treatment of cattle with undifferentiated bovine respiratory disease (BRD) and subsequent feedlot performance and carcass characteristics. In each study, 100 calves with BRD were treated with tulathromycin given SC at 2.5 mg/kg body weight. At the Greeley, CO, and Nebraska study locations, 100 calves were treated with florfenicol given SC at 40 mg/kg body weight, and at the Wellington, CO, and Texas study locations, tilmicosin was given SC at 10 mg/kg body weight. Cure rate, a derived variable that included assessments of mortality, rectal temperature, and attitude and respiratory scores from day 3 to day 28 and day 3 through harvest, was the primary assessment of BRD efficacy. Cure rates of calves treated with tulathromycin were significantly (P < or = .009) higher than those calves treated with florfenicol. At Wellington, CO, the cure rate of calves treated with tulathromycin was significantly higher (P < or = .018) compared with tilmicosin-treated calves. The differences in cure rates between tulathromycin and tilmicosin treatment groups in the Texas study were not significantly different (P > .05). Tulathromycin was more efficacious in the treatment of undifferentiated BRD compared with florfenicol and, in one study, compared with tilmicosin.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Male; Pasteurellosis, Pneumonic; Recurrence; Severity of Illness Index; Thiamphenicol; Treatment Outcome; Tylosin; United States; Weight Gain

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

Actinobacillus pleuropneumoniae, Pasteurella multocida and Streptococcus suis are prevalent bacterial causes of swine infections. Morbidity, mortality and positively impacting the financial burden of infection occurs with appropriate antimicrobial therapy. Increasing antimicrobial resistance complicates drug therapy and resistance prevention is now a necessity to optimize therapy and prolong drug life. Mutant bacterial cells are said to arise spontaneously in bacterial densities of 107-109 or greater colony forming units/ml. Antibiotic drug concentration inhibiting growth of the least susceptible cell in these high density populations has been termed the mutant prevention concentration (MPC). In this study MPC and minimum inhibitory concentration (MIC) values of ceftiofur, enrofloxacin, florfenicol, tilmicosin and tulathromycin were determined against the swine pathogens A. pleuropneumoniae, P.multocida and S. suis. The following MIC90/MPC90 values (mg/L) for 67 A. pleuropneumoniae and 73 P. multocida strains respectively were as follows: A. pleuropneumoniae 0.031/0.5, ≤0.016/0.5, 0.5/2, 4/32, 2/32; P. multocida 0.004/0.25, 0.016/0.125, 0.5/0.5, 8/16, 0.5/1. For 33 S. suis strains, MIC90 values (mg/L) respectively were as follows: 1, 0.25, 4, ≥8 and ≥8. A total of 16 S. suis strains with MIC values of 0.063-0.5 mg/L to ceftiofur and 0.25-0.5 mg/L to enrofloxacin were tested by MPC; MPC values respectively were 0.5 and 1 mg/L respectively. MPC concentrations provide a dosing target which may serve to reduce amplification of bacterial subpopulations with reduced antimicrobial susceptibility. Drug potency based on MIC90 values was ceftiofur > enrofloxacin >florfenicol = tulathromycin > tilmicosin; based on MPC90 values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin.

Topics: Actinobacillus pleuropneumoniae; Animal Husbandry; Animals; Anti-Bacterial Agents; Cephalosporins; Disaccharides; Drug Resistance, Multiple, Bacterial; Enrofloxacin; Heterocyclic Compounds; Microbial Sensitivity Tests; Pasteurella multocida; Streptococcus suis; Swine; Swine Diseases; Thiamphenicol; Tylosin

To determine bactericidal effects of enrofloxacin, florfenicol, tilmicosin, and tulathromycin on clinical isolates of Mannheimia haemolytica at various bacterial densities and drug concentrations.. 4 unique isolates of M haemolytica recovered from clinically infected cattle.. Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined for each drug and isolate. Mannheimia haemolytica suspensions (10(6) to 10(9) CFUs/mL) were exposed to the determined MIC and MPC and preestablished maximum serum and tissue concentrations of each drug. Log10 reduction in viable cells (percentage of cells killed) was measured at various points.. Bacterial killing at the MIC was slow and incomplete. After 2 hours of isolate exposure to the MPC and maximum serum and tissue concentrations of the tested drugs, 91% to almost 100% cell killing was achieved with enrofloxacin, compared with 8% growth to 93% cell killing with florfenicol, 199% growth to 63% cell killing with tilmicosin, and 128% growth to 43% cell killing with tulathromycin over the range of inoculum tested. For all drugs, killing of viable organisms was evident at all bacterial densities tested; however, killing was more substantial at the MPC and maximum serum and tissue drug concentrations than at the MIC and increased with duration of drug exposure. Rank order of drugs by killing potency was enrofloxacin, florfenicol, tilmicosin, and tulathromycin.. Findings suggested that antimicrobial doses that equaled or exceeded the MPC provided rapid killing of M haemolytica by the tested drugs, decreasing opportunities for antimicrobial-resistant subpopulations of bacteria to develop during drug exposure.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Enrofloxacin; Fluoroquinolones; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Pneumonia of Calves, Enzootic; Thiamphenicol; Tylosin; United States

Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Disaccharides; Drug Resistance, Multiple, Bacterial; Enrofloxacin; Fluoroquinolones; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Thiamphenicol; Tylosin; United States

Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including Mannheimia haemolytica and Pasteurella multocida, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis on the ribosome (50% inhibitory concentration [IC(50)], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleotides revealed differences in the interactions of these macrolides within their common ribosomal binding site.

Topics: Anti-Bacterial Agents; Binding Sites; Disaccharides; Escherichia coli; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Molecular Docking Simulation; Mutation; Nucleotides; Pasteurella multocida; Protein Biosynthesis; Ribosomes; RNA, Ribosomal; Subcellular Fractions; Transcription, Genetic; Tylosin; Veterinary Drugs

The purpose of this study was to compare the efficacy and cost-effectiveness of tilmicosin (MIC) versus tulathromycin (DRAX) as a metaphylactic antimicrobial in feedlot calves at moderate risk for bovine respiratory disease (BRD). Calves that received DRAX had significantly (P < or = .05) lower initial BRD treatment rates compared with calves that received MIC. However, there were no significant differences in the BRD relapse rate, railer rate, total mortality rate, BRD mortality rate, average daily gain, and dry matter conversion between the two groups. The economic advantage of the MIC group was Can$8.29/animal. Based on these results, while DRAX was more efficacious in reducing initial treatments for BRD in feedlot calves at moderate risk for disease, MIC was more cost-effective. The lower initial BRD treatment costs in the DRAX group did not offset the higher metaphylactic cost of DRAX.

Topics: Animal Feed; Animals; Animals, Newborn; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cost-Benefit Analysis; Disaccharides; Female; Heterocyclic Compounds; Random Allocation; Treatment Outcome; Tylosin; Weight Gain

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.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Canada; Cattle; Cattle Diseases; Cost-Benefit Analysis; Disaccharides; Eating; Female; Fever; Heterocyclic Compounds; Macrolides; Meat; Oxytetracycline; Random Allocation; Recurrence; Treatment Outcome; Tylosin; Weight Gain