tulathromycin and Pasteurellosis--Pneumonic

The objective of this study was to evaluate the comparative efficacy of tulathromycin at resolving bovine respiratory disease in North American feedlot cattle. This study was a systematic review of published literature. A search was conducted to identify all manuscripts relating to antibiotic treatment of cattle with respiratory disease. Relevant studies reported treatment with tulathromycin of naturally occurring respiratory disease in beef cattle in North America. Studies which failed to use randomization to minimize bias were excluded from the review. The relative risk of retreatment for bovine respiratory disease was calculated for each study included in the final review. Initially, 782 potential manuscripts were identified. After relevance screening and quality assessment, 21 high quality manuscripts were available for analysis. Two peer reviewed publications and two technical reports describing 14 trials compared tulathramycin with tilmicosin or florfenicol. In the meta-analysis of studies comparing tilmicosin with tulathromycin, the summary Mantel-Haenszel relative risk was 0.51 (95% confidence interval 0.45-0.57). It was not possible to calculate a summary Mantel-Haenszel relative risk comparing florfenicol with tulathromycin as the only three studies reported this comparison. When using a meta-analysis to combined data from randomized clinical trials reporting treatment with tulathromycin or either florfenicol or tilmicosin, tulathromycin was associated with an approximately 50% reduction in the risk of re-treatment for bovine respiratory disease compared with treatment with tilmicosin.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Disaccharides; Heterocyclic Compounds; Pasteurellosis, Pneumonic; Randomized Controlled Trials as Topic

Tulathromycin is a novel triamilide antimicrobial that has been approved for use in the treatment and prevention of bovine respiratory disease and the treatment of swine respiratory disease in the European Union and the United States. The agent penetrates gram-negative bacteria well, and it exhibits mixed bacteriostatic and bactericidal activity. Tulathromycin is formulated as a ready-to-use, sterile aqueous solution, and the packaged concentration of 100 mg tulathromycin/ml allows low-volume dosing. This agent is characterized by rapid absorption from the injection site, extensive distribution to tissue, and slow elimination, thereby providing high, prolonged drug concentration in the lungs. Studies show that a single dose of tulathromycin is effective in treating cattle and swine with respiratory disease and in preventing high-risk cattle from developing respiratory disease.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Cattle; Disaccharides; Gram-Negative Bacteria; Gram-Positive Bacteria; Heterocyclic Compounds; Lung; Microbial Sensitivity Tests; Pasteurellosis, Pneumonic; Swine

This clinical trial evaluated the impact of metaphylactic antimicrobial administration 10 d before experimental inoculation with Mannheimia haemolytica (MH) to mitigate pulmonary lesions. Thirty-three crossbreed heifers were procured as a single group and were randomly allocated to 1 of 3 blocks and to treatment, tildipirosin (ZUP; 4 mg/kg) or tulathromycin (DRX; 2.5 mg/kg) or saline (SAL; 1 mL/45.5 kg), within block on arrival at Kansas State University. All trial procedures were staggered by 7-d intervals for each block, resulting in all animals within a block receiving treatment, challenge, and necropsy on the same dates. Heifers within each block received an endoscopic MH challenge 10 d following treatment administration (d 0) and were housed in individual indoor stalls for 3 d postchallenge. Clinical illness scores (CIS), respiration quality scores, appetite scores, and injection site reactions were recorded on all animals from d 0 through d 13. Rectal temperatures were measured once daily on all animals from d 8 through d 13. Heifers were necropsied, and lung lesions were evaluated on d 13. Lung lesion data were evaluated using nonparametric methods (Kruskall-Wallis), and standard least squares models were used to evaluate the remaining variables. The pulmonary lesion scores (percentage of affected lung) ranged from 3.3% to 39.8% for all heifers with 92% (11/12) of ZUP-treated heifers having <10% lesions. Tildipirosin-treated heifers had lower (P < 0.05) lung lesion scores when compared with DRX- and SAL-treated heifers. Lung weight expressed as a percentage of BW was lower (P < 0.05) in ZUP heifers compared to DRX- and SAL-treated heifers. The probability of receiving abnormal CIS, appetite scores, and respiratory scores was lower (P < 0.05) in ZUP-treated heifers compared to DRX- and SAL-treated animals. This study showed that heifers treated with tildipirosin 10 d before MH challenge have less pulmonary damage and fewer clinical signs of illness compared to heifers treated with DRX or SAL.

Topics: Animals; Anti-Infective Agents; Antibiotic Prophylaxis; Cattle; Disaccharides; Female; Heterocyclic Compounds; Lung; Mannheimia haemolytica; Pasteurellosis, Pneumonic; Tylosin

Topics: Animals; Anti-Bacterial Agents; Disaccharides; Feces; Goat Diseases; Goats; Heart Rate; Heterocyclic Compounds; Injections, Subcutaneous; Male; Pasteurellosis, Pneumonic

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.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Nebraska; Pasteurellosis, Pneumonic; Recurrence; Thiamphenicol; Treatment Outcome; 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

The clinical efficacy of tulathromycin in the treatment of natural outbreaks of swine respiratory disease (SRD) was evaluated at five European sites. Pigs (1 to 6 months of age) exhibiting clinical signs of SRD were treated intramuscularly with tulathromycin (n = 247) at 2.5 mg/kg on day 0 versus either tiamulin (n = 102) at 15 mg/kg on days 0, 1, and 2 (Germany, the Netherlands, and the United Kingdom) or florfenicol (n = 20) at 15 mg/kg on days 0 and 2 (France). Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma hyopneumoniae infections were the most frequently diagnosed pathogens. For both tulathromycin-treated animals and those treated with tiamulin or florfenicol, there were significant (P = .0001) reductions in mean rectal temperature and the severity of abnormal clinical signs on days 2 and 10 compared with day 0. There were no significant differences (P > .05) between treatments in average daily weight gain. Tulathromycin was found to be safe and highly effective in the treatment of natural outbreaks of SRD.

Topics: Animals; Anti-Bacterial Agents; Disaccharides; Disease Outbreaks; Diterpenes; Europe; Heterocyclic Compounds; Injections, Intramuscular; Pasteurellosis, Pneumonic; Severity of Illness Index; Swine; Swine Diseases; Thiamphenicol; Treatment Outcome

Tulathromycin, a novel triamilide antimicrobial, was evaluated for treatment of swine respiratory disease (SRD) in field efficacy studies involving 720 pigs in six North American swine herds. In each study, feeder pigs with clinical SRD were randomly assigned in equal numbers to a group treated with tulathromycin given as a single injection at 2.5 mg/kg of body weight or to a saline-treated control group. Four of the studies included a third group treated with ceftiofur sodium for 3 consecutive days at 3 mg/kg of body weight. Pigs were treated on day 0 and evaluated for treatment response on day 7. In each study, 10 or more nontreated pigs and saline-treated pigs that did not respond to treatment underwent necropsies to obtain lung samples that were evaluated for SRD pathogens. The overall cure rate was 46.4% for saline-treated pigs, 71.1% for tulathromycin-treated pigs, and 63.1% for ceftiofur-treated pigs. The cure rate for tulathromycin-treated pigs was significantly higher than for saline-treated pigs (P = .0116). Mortality from SRD occurred in 24 control pigs, seven tulathromycin-treated pigs, and one ceftiofur-treated pig. The mortality rate was significantly lower for both the tulathromycin- and ceftiofur-treated pigs compared with those treated with saline (P = .0148 and P = .0195, respectively). Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Mycoplasma hyopneumoniae, bacteria commonly associated with SRD, were isolated from SRD-affected pigs. Under field conditions, tulathromycin injectable solution given as a single IM dose of 2.5 mg/kg of body weight was safe and effective in the treatment of SRD.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Disaccharides; Female; Gram-Negative Bacteria; Heterocyclic Compounds; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Mycoplasma hyopneumoniae; Pasteurellosis, Pneumonic; Severity of Illness Index; Swine; Swine Diseases; Treatment Outcome; United States

Bovine Respiratory Disease (BRD) is a major threat to animal health and welfare in the cattle industry. Strains of Mannheimia haemolytica (Mh) that are resistant to multiple classes of antimicrobials are becoming a major concern in the beef industry, as the frequency of isolation of these strains has been increasing. Mobile genetic elements, such as integrative conjugative elements (ICE), are frequently implicated in this rapid increase in multi-drug resistance. The objectives of the current study were to determine the genetic relationship between the isolates collected at arrival before metaphylaxis and at revaccination after metaphylaxis, to identify which resistance genes might be present in these isolates, and to determine if they were carried on an ICE. Twenty calves culture positive for Mh at arrival and revaccination were identified, and a total of 48 isolates with unique susceptibility profiles (26 from arrival, and 22 from revaccination) were submitted for whole-genome sequencing (WGS). A phylogenetic tree was constructed, showing the arrival isolates falling into four clades, and all revaccination isolates within one clade. All revaccination isolates, and one arrival isolate, were positive for the presence of an ICE. Three different ICEs with resistance gene modules were identified. The resistance genes aphA1, strA, strB, sul2, floR, erm42, tetH/R, aadB, aadA25, blaOXA-2, msrE, mphE were all located within an ICE. The gene bla-ROB1 was also present in the isolates, but was not located within an ICE.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Drug Resistance, Multiple, Bacterial; Genetic Variation; Genome, Bacterial; Heterocyclic Compounds; Immunization, Secondary; Interspersed Repetitive Sequences; Mannheimia haemolytica; Microbial Sensitivity Tests; Pasteurellosis, Pneumonic; Phylogeny; Vaccination; Whole Genome Sequencing

The in vitro activity of tulathromycin was evaluated against common bovine and porcine respiratory pathogens collected from outbreaks of clinical disease across eight European countries from 1998 to 2001. Minimum inhibitory concentrations (MICs) for one isolate of each bacterial species from each outbreak were determined using a broth microdilution technique. The lowest concentrations inhibiting the growth of 90% of isolates (MIC90) for tulathromycin were 2 microg/ml for Mannheimia (Pasteurella) haemolytica, 1 microg/ml for Pasteurella multocida (bovine), and 2 microg/ml for Pasteurella multocida (porcine) and ranged from 0.5 to 4 microg/ml for Histophilus somni (Haemophilus somnus) and from 4 to 16 microg/ml for Actinobacillus pleuropneumoniae. Isolates were retested in the presence of serum. The activity of tulathromycin against fastidious organisms was affected by culture conditions, and MICs were reduced in the presence of serum.

Topics: Actinobacillus pleuropneumoniae; Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Europe; Gram-Negative Bacteria; Haemophilus somnus; Heterocyclic Compounds; In Vitro Techniques; Mannheimia haemolytica; Microbial Sensitivity Tests; Pasteurella multocida; Pasteurellosis, Pneumonic; Swine; Swine Diseases