Meta-analysis of the effects of monensin in beef cattle on feed efficiency, body weight gain, and dry matter intake.

A meta-analysis of the impact of monensin on growing and finishing beef cattle was conducted after a search of the literature. A total of 40 peer-reviewed articles and 24 additional trial reports with monensin feeding in beef cattle were selected, after meeting apriori quality criteria. Data for each trial were extracted and analyzed using meta-analysis software in STATA. Estimated effect size of monensin was calculated for feed efficiency (FE), ADG, and DMI. Monensin use in growing and finishing beef cattle reduced DMI (P < 0.001) and improved both ADG (P < 0.001) and FE (P < 0.001). The average concentration of monensin in feed across studies was 28.1 mg/kg feed (100% DM) and this resulted in approximately a 6.4% (but only 2.5 to 3.5% in the last 2 decades) increase in FE, 3% decrease in DMI, and 2.5% increase in ADG. All 3 outcomes displayed moderate and significant heterogeneity of monensin response (I(2), which is a measure of variation beyond chance, = 29% for FE, 42% for DMI, and 23% for ADG); therefore, random effects models were used for those outcomes. There were no single influential studies that overweighted the findings for any outcome. Meta-regression analysis of the effect sizes obtained from these data showed that dietary factors, dose, and study design were influential in modifying effect size of monensin treatment. Use of corn silage in the diet influenced the effect size of monensin for DMI and FE, with diets containing corn silage resulting in a greater improvement in FE and a larger effect on reducing DMI. Studies conducted to assess multiple doses of monensin showed similar effects to the use of corn silage in the diet. Studies conducted in the United States or with higher ADG in control animals (>1.17 kg/d) showed less effect of monensin on ADG. Pen-level studies showed a greater monensin increase on ADG than did those conducted on individual animals. Linear effect of monensin dose was observed for FE, DMI, and ADG outcomes, with greater effects on improving FE and reducing DMI with larger doses of monensin but lesser improvement in ADG with increasing dose. These findings confirm that monensin improves FE in growing and finishing beef cattle, and that this effect is linear with dose.

Tilmicosin induces apoptosis in bovine peripheral neutrophils in the presence or in the absence of Pasteurella haemolytica and promotes neutrophil phagocytosis by macrophages.

Pathogen virulence factors and inflammation are responsible for tissue injury associated with respiratory failure in bacterial pneumonia, as seen in the bovine lung infected with Pasteurella haemolytica. Tilmicosin is a macrolide antibiotic used for the treatment of bovine bacterial pneumonia. Recent evidence suggests that tilmicosin-induced neutrophil apoptosis may have anti-inflammatory effects. Using bovine leukocytes, we sought to define whether live P. haemolytica affected tilmicosin-induced neutrophil apoptosis, assessed the proapoptotic effects of tilmicosin in comparison with other drugs, and characterized its impact on phagocytic uptake of neutrophils by macrophages. Induction of apoptosis in the presence or absence of P. haemolytica was assessed by using an enzyme-linked immunosorbent assay for apoptotic nucleosomes. In addition, fluorescent annexin-V staining identified externalized phosphatidylserine in neutrophils treated with tilmicosin, penicillin, ceftiofur, oxytetracycline, or dexamethasone. Neutrophil membrane integrity was assessed by using propidium iodide and trypan blue exclusion. As phagocytic clearance of apoptotic neutrophils by macrophages contributes to the resolution of inflammation, phagocytosis of tilmicosin-treated neutrophils by esterase-positive cultured bovine macrophages was assessed with light microscopy and transmission electron microscopy. Unlike bovine neutrophils treated with penicillin, ceftiofur, oxytetracycline, or dexamethasone, neutrophils exposed to tilmicosin became apoptotic, regardless of the presence or absence of P. haemolytica. Tilmicosin-treated apoptotic neutrophils were phagocytosed at a significantly greater rate by bovine macrophages than were control neutrophils. In conclusion, tilmicosin-induced neutrophil apoptosis occurs regardless of the presence or absence of live P. haemolytica, exhibits at least some degree of drug specificity, and promotes phagocytic clearance of the dying inflammatory cells.

Anti-inflammatory benefits of tilmicosin in calves with Pasteurella haemolytica-infected lungs.

OBJECTIVES: To determine whether tilmicosin alters neutrophil infiltration or function, induces neutrophil apoptosis, and affects accumulation of leukotriene B4 (LTB4) or tumor necrosis factor-alpha (TNF-alpha) in lungs of calves experimentally infected with Pasteurella haemolytica. ANIMALS: 12 weight-ranked Holstein calves. PROCEDURE: Calves were given 25% propylene glycol vehicle (n = 5) or tilmicosin (10 mg/kg of body weight; n = 6) subcutaneously, 18 hours and 15 minutes before intratracheal infection with 2 x 10(8) P haemolytica organisms. Two unmanipulated calves served as controls in some experiments. Rectal temperatures were recorded 15 minutes before, and at 3-hour intervals after infection for 24 hours. Samples obtained from bronchoalveolar lavage performed 3 and 24 hours after infection were used to assess colonization by P haemolytica, and neutrophil infiltration. Neutrophil phagocytosis of P haemolytica, membrane leakage as determined by trypan blue exclusion, oxidative function as determined by nitro blue tetrazolium reduction, and apoptosis, using electron microscopy and DNA fragmentation ELISA, were determined. SOluble TNF-alpha and LTB4 were measured from supernatants from bronchoalveolar lavage samples, using ELISA. RESULTS: Treatment with tilmicosin resulted in significant (P < 0.05) clearance of P haemolytica and neutrophil apoptosis at 3 hours, and decreased concentration of LTB4 at 24 hours. Rectal temperatures, neutrophil infiltration, phagocytosis, oxidative functions, membrane leakage, and soluble TNF-alpha concentrations were not significantly affected by tilmicosin. CONCLUSION: Tilmicosin effectively controlled P haemolytica infection, induced neutrophil apoptosis, reduced pulmonary inflammation, and did not affect neutrophil infiltration or function. CLINICAL RELEVANCE: By inducing neutrophil apoptosis, tilmicosin prevents further amplification of inflammatory injury in P haemolytica-infected lungs.

Treatment of experimentally induced pneumonic pasteurellosis of young calves with tilmicosin.

Twenty four (24) healthy male Holstein calves (< 70 kg) were each experimentally infected by intrabronchial inoculation of 4.0 x 10(9) viable cells of Pasteurella haemolytica-AI (B122) at Time = 0 h. At 1 h following inoculation animals received either: 1) Sham treatment with sterile 0.85% saline SC (n = 12); or 2) a single injection of 10 mg tilmicosin per kg body weight (n = 12). Calves that were non-infected and tilmicosin-treated were also included for determining tilmicosin concentrations in serum and lung tissue at 1, 2, 4, 6, 8, 24, 48, and 72 h (n = 3-per time). In the infected calves, response to therapy was monitored clinically. Serum samples were collected for determination of tilmicosin concentrations using HPLC. Any animal becoming seriously ill was humanely killed. Complete necropsy examinations were performed on all animals and included gross pathologic changes, bacteriologic analysis, histopathology, and determination of pulmonary concentrations of tilmicosin. Tilmicosin treated animals responded significantly better to therapy than saline-treated control calves. Clinical assessment of calves during the study indicated that tilmicosin-treated calves had significantly improved by T = 8 h compared to satine-treated animals (P < 0.05). At necropsy tilmicosin-treated calves had significantly less severe gross and histological lesions (P < 0.05) of the pulmonary tissue. Of the 12 saline-treated calves, 92% (11/12) had Pasteurella haemolytica-A1 in lung tissue, while of the tilmicosin-treated calves 0% (0/12) cultured positive for P. haemolytica. Mean (+/- standard error) serum tilmicosin concentrations in infected calves peaked at 1 h post-injection (1.10 +/- 0.06 micrograms/mL) and rapidly decreased to 0.20 +/- 0.03 microgram/mL, well below the MIC of 0.50 microgram/mL for P. haemolytica-A1 (B122), by 12 h. These serum concentrations were very similar to serum concentrations of tilmicosin in non-infected tilmicosin-treated calves. Lung tissue concentrations of the antibiotic were comparatively high, even at 72 h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentrations at 72 h were significantly higher in experimentally infected calves than in non-infected tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was effective in treating experimentally-induced pneumonic pasteurellosis as determined by alleviation of clinical signs, pathological findings at post mortem, and presence of viable bacteria from the lung. Concentrations substantially above MIC for P. haemolytica were present in lung tissue even at 72 h following a single subcutaneous injection of 10 mg tilmicosin per kg body weight.

Use of tilmicosin for treatment of pasteurellosis in rabbits.

OBJECTIVES: To determine tilmicosin concentrations in serum and tissues of rabbits given a single dose of 25 mg of tilmicosin/kg of body weight. To examine the effects of tilmicosin treatment (25 mg/kg, s.c.) in rabbits with pasteurellosis. PROCEDURE: After receipt of tilmicosin, healthy New Zealand White female rabbits (n = 3 at each time) were euthanatized at 2, 4, 8, 24, 48, and 72 hours for collection of blood samples and tissue specimens; 4 rabbits served as untreated controls. Rabbits (male and female) with pasteurellosis (n = 42) also were treated. Tilmicosin concentration was determined in serum, lung, and uterine tissues. Rabbits with pasteurellosis were treated with tilmicosin. Response was monitored, using bacteriologic culturing and antibiotic resistance and susceptibility testing, and by scoring clinical signs of disease. RESULTS: Serum tilmicosin concentration reached 1.91 +/- 0.18 micrograms/ml after 2 hours, decreased to 0.77 +/- 0.07 microgram/ml by 8 hours, and was below minimum inhibitory concentrations for Pasteurella multocida at 24 hours. Terminal half-life in serum was 5.97 hours. Lung and uterus concentrations were 14.43 +/- 1.34 and 11.57 +/- 0.09 ppm at 2 hours, and were 5.10 +/- 1.05 and 8.87 +/- 1.66 ppm at 24 hours, respectively. 69% (29/42) of rabbits with pasteurellosis responded favorably in 3 days. Second treatment was required in 31% (13/42), and 5 of these rabbits had clinical signs on day 6; 2 of these 5 had improved. Treatment success rate was 93% (39/42). Of the rabbits that were culture positive on day 0, 35% (6/ 17) remained positive on day 3. 1 of 6 rabbits was culture positive on day 6. CONCLUSION: Tilmicosin (25 mg/kg, s.c.) was an effective treatment for pasteurellosis in New Zealand White rabbits. CLINICAL RELEVANCE: Tilmicosin treatment of pasteurellosis in rabbits is useful in research rabbits and in those destined for meat production. A single dose of antibiotic minimizes stress-associated handling.

Effects of feed treatment and gender on the flavour and texture profiles of cured and uncured pork cuts. I. Ractopamine treatment and dietary protein level.

Equal numbers of barrows (64) and gilts (64) were randomly allocated to two separate diets containing 17·6 and 19·6% crude protein. Subsequently within each gender/diet treatment group, pigs were equally and randomly assigned to two ractopamine treatment groups (i.e. 0 or 20 ppm ractopamine), resulting in 16 pigs per gender/diet/ractopamine subgroup. The feeding trial lasted an average of 41 days, and the pigs went on trial at an average weight of 64·5 kg and were slaughtered at an average weight of 98·2 kg. Five barrows and five gilts were subsampled at random from each gender/diet/ractopamine subgroup for palatability evaluations. Comprehensive palatability evaluations were conducted on both cured and uncured pork cuts. Results revealed no meaningful differences in flavour, texture, or cooking properties attributable to dietary protein level (17·6 vs 19·6% crude protein) or to ractopamine. Thus, within the context of conditions employed in the present study, ractopamine can be administered with different dietary crude protein levels to improve production efficiency and carcass composition, without influencing palatability and cooking properties or consumer acceptance. Gender effects have been reported elsewhere (Jeremiah et al., 1994).

Effects of feed treatment and gender on the flavour and texture profiles of cured and uncured pork cuts. II. Ractopamine treatment and dietary protein source.

A total of 128 barrows and 128 gilts were equally and randomly allocated to two separate barley-based diets containing two distinct protein sources (soybean meal and canola meal). Subsequently, the pigs within each gender/ diet treatment subgroup were equally and randomly assigned to two ractopamine treatment groups (0 or 20 ppm). The feeding trial lasted an average of 42 days. The pigs went on trial at an average weight of 67·9 kg and were slaughtered at an average weight of 101·9 kg. Ten pigs selected at random from each gender/diet/ractopamine subgroup were utilized for detailed palatability evaluation. These comprehensive palatability evaluations were conducted on both cured and uncured pork cuts. Results revealed no differences of practical importance in flavour, texture, or cooking properties attributable to dietary protein source or to administration of ractopamine, despite the fact a few statistically significant differences were observed. Thus, ractopamine can be administered with different dietary protein sources to improve production efficiency and improve carcass composition, without influencing palatability and cooking properties, or consumer acceptance. Gender effects have been reported elsewhere (Jeremiah et al., 1994b).

The effects of feed treatment and gender on the flavour and texture profiles of cured and uncured pork cuts. III. Effects of gender.

A total of 384 pigs (192 barrows and 192 gilts) was utilized to evaluate the effects of gender on the flavour and texture profiles of cured and uncured pork cuts. Observed differences in all cuts indicated the incidence, intensity, and/or order of appearance of flavour character notes were more appropriate, in samples from barrows than in samples from gilts; differences observed in all cuts also indicated textural properties were more appropriate, in samples from barrows than in samples from gilts. However, the magnitude of such differences in all cuts, was insufficient to influence flavour and texture amplitude ratings. Consequently, even though cuts from barrows are marginally superior to cuts from gilts in both flavour and texture, this superiority is unlikely to be of practical importance. The effects of ractopamine treatment and protein level (Jeremiah et al., 1994a) and ractopamine treatment and protein source (Jeremiah et al., 1994b) have been previously covered.

Prophylactic efficacy of tilmicosin for bovine respiratory tract disease.

The prophylactic administration of injectable tilmicosin for pneumonia in weaned beef calves was investigated in 1,806 animals. Comparisons were made among calves receiving an "on-arrival" injection of tilmicosin, calves receiving a single injection of long-acting oxytetracycline, and calves receiving no prophylaxis. Morbidity and mortality attributable to pneumonia, morbidity and mortality attributable to all causes, and case fatality were significantly lower in the group of calves that received tilmicosin, compared with calves that received long-acting oxytetracycline and calves that received no prophylactic antibiotic. Mean time to initial pneumonia treatment was significantly extended in calves that received prophylaxis, compared with those that received no antibiotic on arrival at the feedlot. Calves that received tilmicosin gained significantly more weight than calves that received oxytetracycline. Calves that were not treated for pneumonia during the trial period gained significantly more weight than did those calves that were treated for pneumonia regardless of experimental group. The majority of mortalities were attributable to fibrinous pneumonia (31/34). Important bacterial isolates (Pasteurella spp, Haemophilus somnus, Actinomyces pyogenes) obtained at necropsy did not have resistance to tilmicosin in association with administration of tilmicosin as prophylaxis for pneumonia. However, bacterial resistance to trimethoprim/sulfonamide and to oxytetracycline were commonly found in these postmortem isolates.

Tilmicosin as a single injection treatment for respiratory disease of feedlot cattle.

Tilmicosin, a new semi-synthetic macrolide antibiotic, was evaluated in eight field trials as a single subcutaneous injection at dosages of 0 (placebo), 5, 10 and 20 mg/kg for the treatment of naturally occurring respiratory disease in feedlot cattle. Animals for these trials were selected from large groups of recently-shipped feeder cattle at the time clinical signs of respiratory disease and body temperature of 40.6 degrees C or higher were observed. Treated animals were evaluated daily for 10 days and finally at day 28. Each animal was weighed on the first day and again on day 28. Animals that died were necropsied. All treatment dosages were effective in significantly lowering mortality, improving weight gains, lowering body temperature, and reducing the severity of clinical signs when compared to the placebo-treated controls. Body temperature was the only variable with statistically significant differences among the dose levels.