tilmicosin and Bovine-Respiratory-Disease-Complex

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

Nitric oxide has bactericidal and virucidal properties. Nasal instillation of a nitric oxide releasing solution (NORS) on arrival at the feedlot was recently reported as inferior to a parenteral injection of tilmicosin (macrolide antibiotic) for control of bovine respiratory disease (BRD) in cattle at high-risk of developing BRD. We hypothesized that this inferiority was due to differences between treatments with regards to their effects on the nasopharyngeal microbiota. The objective was to compare nasal instillation of NORS versus parenteral administration of tilmicosin regarding their effects on the nasopharyngeal microbiota of feedlot cattle at high-risk of developing BRD. Culture-independent community profiling (16S rRNA sequencing) and culture-based methods were used to evaluate treatment effects. High-risk Angus-cross heifers (n=20) were randomly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for prevention of BRD. Heifers were sampled using guarded deep nasal swabs immediately prior to treatment (day 0) and on days 1, 5 and 10 after treatment. Based on culture-independent community profiling, there was a distinct shift in composition of the nasopharyngeal microbiota during the first 10 d after arrival, with 116 OTUs changing over time, but no difference between treatment groups. However, culture-based methods detected a difference between treatment groups, with more cattle culture-positive for Pasteurellaceae in the NORS group at day 5 post-treatment. This difference in ability to inhibit colonization of the nasopharynx by Pasteurellaceae may be the basis for NORS being inferior to tilmicosin for control of BRD in high-risk cattle.

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Female; Microbiota; Nasopharynx; Nitric Oxide; Risk Factors; RNA, Bacterial; RNA, Ribosomal, 16S; Tylosin

Nitric oxide, a molecule produced in most mammalian cells, has bactericidal and virucidal properties. Nasal instillation of a nitric oxide releasing solution (NORS) on arrival at the feedlot was recently reported as non-inferior to a parenteral injection of a macrolide antibiotic, tilmicosin, for control of bovine respiratory disease (BRD) in cattle at low-to-moderate risk of developing BRD. The objective of this study was to evaluate whether NORS was non-inferior to tilmicosin for control of BRD in cattle at high-risk of developing BRD (the target population for many BRD control programs). High-risk Angus-cross heifers (n=840) were randomly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for BRD control. Non-inferiority was assessed by calculating the difference in prevalence of heifers diagnosed with BRD during the first 40 d after arrival between NORS and tilmicosin treatment groups. The non-inferiority margin (δ) was set at 8.5%. Thirty-six and 19% of heifers were diagnosed with BRD in the NORS and tilmicosin groups, respectively. Because the lower bound of the 2-sided 95% confidence interval (CI) of the difference in BRD prevalence between the 2 treatment groups (17%; 95% CI=11-23%) was higher than δ, an inferiority of NORS was concluded. Although on-arrival nasal administration of NORS can be viewed as a more rational control strategy than parental injection of antibiotics, further research is needed to improve NORS efficacy before it can be recommended to prevent BRD in high-risk cattle.

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Female; Nitric Oxide; Prevalence; 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

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

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 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