Efficacy dose determination study of tilmicosin phosphate in feed for control of pneumonia caused by Actinobacillus pleuropneumoniae in swine.

OBJECTIVE: To determine the effective dosage of tilmicosin phosphate when fed to pigs for the control of pneumonia attributable to Actinobacillus pleuropneumoniae. DESIGN: Randomized complete block design, with initial weight as the blocking factor. ANIMALS: Seeder pigs were used to infect clinically normal male and female pigs weighing between 13.6 and 36.3 kg at each of 4 trials. PROCEDURE: Five doses of tilmicosin phosphate (0, 100, 200, 300, and 400 micrograms/g) were fed to pigs for 21 days. Pigs received experimental feeds 7 days before the seeder pigs were placed into pens. Feeding continued for an additional 14 days, with seeder pigs removed 3 to 8 days after placement. All pigs were euthanatized and necropsied, with lung bacterial flora and percentages of pneumonic involvement determined. RESULTS: Improvement in clinical impression score, daily rectal temperature, and weight gain were seen for all doses of tilmicosin, compared with controls. For the same variables, tilmicosin administered at 200 to 400 micrograms/g resulted in improvements over the 100 micrograms/g dose. CONCLUSIONS: Data indicate that tilmicosin phosphate fed to pigs at 200 to 400 micrograms/g is effective in controlling and preventing A pleuropneumoniae-induced pneumonia, when administered in feed for 21 days.

Clinical field trials with tilmicosin phosphate in feed for the control of naturally acquired pneumonia caused by Actinobacillus pleuropneumoniae and Pasteurella multocida in swine.

OBJECTIVE: To determine and evaluate the efficacy of the dose range of tilmicosin phosphate fed to pigs for control of pneumonia attributable to Actinobacillus pleuropneumoniae during episodes of clinical disease in commercial herds. DESIGN: 12 trials were run in 9 geographic locations in herds with a history of pneumonia caused by A pleuropneumoniae. ANIMALS: Clinically normal male and female pigs of various body weights. PROCEDURE: Two doses of tilmicosin phosphate (200 and 400 micrograms/g) and a 0 dose were administered in the feed for 21 days. Variables for determining efficacy were daily independent composite clinical impression score, individual pig weight, mortality, percentage of pneumonic involvement, and frequency of isolation of bacterial pathogens. RESULTS: Medicated pigs had significantly lower mortality attributed to pneumonia than did nonmedicated pigs. In trials with confirmed pneumonia caused by A pleuropneumoniae or Pasteurella multocida, weight gain, feed conversion, and clinical impression scores were significantly improved in the pigs receiving 200 or 400 micrograms/g of tilmicosin, compared with nonmedicated pigs. CONCLUSIONS: The clinical field trials reported here confirm that tilmicosin in the feed at 200 micrograms/g is effective for control of swine pneumonia attributable to A pleuropneumoniae or P multocida. CLINICAL RELEVANCE: Under the moderate natural challenge conditions encountered, tilmicosin at 400 micrograms/g was not different from tilmicosin at 200 micrograms/g.

Effect of bentonite incorporated in a feed ration with tilmicosin in the prevention of induced Mycoplasma gallisepticum airsacculitis in broiler chickens.

A factorial arrangement of tilmicosin and bentonite was evaluated for efficacy in broiler chickens infected with Mycoplasma gallisepticum and correlated to tilmicosin recovery in a feed assay method. Tilmicosin at 300-500 g/ton prevented development of airsacculitis. The addition of 2% bentonite to the ration caused tilmicosin at 300 g/ton to be ineffective in controlling air-sac lesions, whereas 400 and 500 g/ton were moderately effective. Six percent bentonite rendered tilmicosin completely ineffective at all dose levels. There was a direct correlation between the percentage of bentonite in the feed rations, the percentage of the tilmicosin recovered in the assay procedure, and the increased incidence of air-sac lesions.

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.

Fibrinogen-degrading proteins from Haemonchus contortus used to vaccinate sheep.

Sixteen nonsibling sheep, approximately 12 months old, that were raised in a helminth-free environment, were used for 2 protection studies 6 months apart. Sheep were vaccinated weekly for 5 weeks by IM injection of fibrinogen-degrading proteins derived from the intestinal tract of adult Haemonchus contortus. Ten days after the last vaccination, sheep were given 2,500 infective H contortus larvae by intraruminal injection. Vaccinated sheep produced specific antibodies, and were protected from the worm challenge. Significant differences in mean fecal worm egg counts for 56 days after worm challenge, in mean numbers of H contortus worms, and female fecundity ratios at necropsy were detected in vaccinated sheep, compared with those in control sheep. These data suggest that the fibrinogen-degrading proteins have a protective role in vaccination of sheep against H contortus.

Protective studies in sheep immunized with cuticular collagen proteins and peptides of Haemonchus contortus.

Twenty-eight nonsibling sheep aged approximately 12 months and raised in a helminth-free environment were used in two protection studies. Immunizations were conducted by two intramuscular injections 30 days apart with a synthetic 18AA cuticle collagen peptide and native cuticle collagens derived from the third- and fourth-stage larvae of Haemonchus contortus. Ten days following the last immunization, the sheep were each given 500 infective H. contortus larvae per day for five consecutive days by intraruminal injection. Both collagen materials induced antibodies reactive with cuticle collagens; however, neither induced reproducible protection to H. contortus infections in vaccinated/infected sheep. In the most extensive test, there were no statistical differences in mean faecal worm egg count for 56 days post worm challenge, in mean numbers of H. contortus and female fecundity ratios at necropsy of immunized and unimmunized sheep. Failure to reproducibly immunize sheep with cuticle collagens may be due to the inability of antibodies or host immune cells to reach the collagen epitopes in the nematode cuticle without prior surface coat removal as postulated in human nematode studies.

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.

Effect of narasin and roxarsone combinations on Eimeria tenella infections in floor pen-raised broilers.

A series of four floor pen trials was conducted to evaluate the effects of narasin and roxarsone, both alone and in combination, on their capacity to control severe Eimeria tenella infections in broilers. Three levels of narasin (0, 60, and 80 ppm) were fed to chickens receiving either 0, 25, or 50 ppm roxarsone in a factorial design. Cecal coccidiosis was induced by seeding the litter with ionophore-tolerant and ionophore-sensitive strains of E. tenella. After 8 days, 10 birds/pen were killed and their cecal lesions scored. Performance (body weight and feed consumption) and mortality were measured at the termination of the trials. Narasin reduced the severity of cecal coccidiosis as measured by a reduction in cecal lesions and an improvement in bird performance. Roxarsone also reduced cecal lesion scores. The highest level of roxarsone (50 ppm) in combination with 60 or 80 ppm narasin produced additive responses in the control of E. tenella infections. Maximum performance was obtained when narasin alone was fed at 80 ppm; drug combinations improved performance when compared with that of nontreated or roxarsone only-medicated groups.

Single-dose treatment of neonatal calf pneumonia with the new macrolide antibiotic tilmicosin.

Tilmicosin, a new macrolide antibiotic, 20-deoxo-20-(3,5-dimethylpiperidin-l-yl)desmycosin, formerly identified as EL-870, has been evaluated in three experiments as a single subcutaneous injection at dosages of 10, 20 or 30 mg/kg for the treatment of naturally occurring pneumonia in neonatal calves. Male Holstein calves, under five days of age, were shipped from Wisconsin and housed in pens. They were assigned sequentially to a treatment group when their temperature was greater than or equal to 39.7 degrees C for two consecutive days or greater than or equal to 39.7 degrees C and signs of respiratory disease were present. Clinical signs were evaluated daily for 14 days after the tilmicosin treatment. Calves that died and those that survived for the 14 day experimental period were examined post mortem. Treatment with tilmicosin was effective at all dosage levels, as determined by significant (P less than or equal to 0.05) reductions in body temperature within 24 hours, in the number of animals that died, in the incidence and severity of clinical signs, in the number of Pasteurella species found in lung tissue and in the severity of the pneumonic lesions. In two of the three experiments severe outbreaks of cryptosporidiosis resulted in significant mortalities within a few days after the arrival of the calves. Treatment with tilmicosin was effective against respiratory disease even in the presence of this severe concurrent disease.

Anticoccidial efficacy of narasin in floor pen trials.

Narasin is effective against all species of chicken coccidia when tested in short-term battery cage experiments. The efficacy of narasin at concentrations of 20, 40, 60, 80, and 100 ppm was evaluated in ten floor pen trials in which commercial broiler production conditions were simulated. To provide intentional exposure to different levels of coccidia challenge, the litter of some pens was seeded with oocysts of each of the pathogenic species of chicken coccidia, whereas some pens were left nonseeded. Weight gain, feed efficiency, and lesion score data from the ten trials were analyzed as one randomized block experiment. Medication with narasin resulted in a significant reduction in lesion scores and significant improvement in weight gain and feed:gain ratios when compared with scores and gain of nonmedicated controls for both seeded and nonseeded pens. Each increase in narasin concentration up to 100 ppm for the seeded pens and up to 80 ppm for the nonseeded pens resulted in a significant reduction in cecal lesion scores. Although maximum weight gain in the seeded pens was obtained with 40 ppm narasin, concentrations greater than or equal to 60 ppm narasin were significantly better than the 40 ppm concentration in improving feed:gain ratios. These results confirm the effectiveness of narasin in controlling coccidiosis in broilers exposed to oocysts in the litter of floor pens. Furthermore, a clear relationship between the response to narasin and the level of oocyst challenge was demonstrated.

Anticoccidial efficacy of narasin in battery cage trials.

Narasin is a polyether monocarboxylic acid antibiotic produced by Streptomyces aureofaciens. An extensive series of battery cage trials was conducted to evaluate the efficacy of narasin against recent field isolates of the pathogenic species of chicken coccidia. Statistical analyses of the results of these studies revealed that each successive increase in the concentration of narasin produced a significant reduction in the severity of cecal and intestinal lesions when compared with those in infected nonmedicated controls. Increasing the concentration of narasin also produced significant improvements in weight gain and feed efficiency when compared to gain and feed efficiency of infected nonmedicated controls. Maximum weight gain of birds infected with Eimeria tenella alone was obtained at a narasin concentration of 60 ppm, but birds infected with E. tenella plus intestinal species of coccidia, when medicated with 80 ppm narasin had weight gains significantly greater than those of birds medicated with 60 ppm narasin. Weight gain improvement decreased at narasin concentrations greater than or equal to 100 ppm. Results of these studies confirm the effectiveness of narasin in controlling coccidial infections produced by recent field isolates of the pathogenic species of chicken coccidia.

Field experience trials comparing narasin and monensin.

Narasin is effective against all species of chicken coccidia when tested in battery cage and floor pen studies. To confirm the efficacy of narasin under practical broiler production conditions, the drug was fed at concentrations of 60 ppm or 80 ppm to broiler chickens being raised by six different commercial broiler producers in five different geographic areas. Monensin was fed in each trial at a concentration of 100 ppm or 121 ppm as a reference control. The usual management practices of each of the integrated broiler companies were followed throughout the respective trials. Nine trials were conducted and approximately 100,000 broilers were tested for each treatment. No adverse reactions attributable to treatments were observed in any of the trials, and performance results obtained with narasin-medicated birds were generally comparable with those obtained with monensin-medicated birds in the same trial. These findings support the conclusion that narasin at final feed concentrations in the range of 60 to 80 ppm can be safely and effectively used as an anticoccidial agent in commercial broiler production facilities.

Processing yields and meat flavor of broilers fed a mixture of narasin and nicarbazin as an anticoccidial agent.

Processed yields (percent hot carcass) and cooked meat flavor of broilers fed 100 ppm of an anticoccidial agent (a mixture of 50 ppm narasin and 50 ppm nicarbazin) were compared with yields of birds fed a ration without the anticoccidial agent. Broilers were processed at 7 wk of age (49 days) after a 4-day withdrawal from the anticoccidial agent for the treated birds. The flavor of meat was evaluated by a 12-member sensory panel. Meat was either deep fat-fried or oven roasted. Sensory evaluations were made on freshly cooked samples and on cooked meat refrigerated for 24 h and reheated. The anticoccidial agent did not produce a difference (P greater than .05) in the hot carcass yields of the broilers as compared with control birds fed the nonmedicated diet. Analyses of triangle test data for flavor evaluations by two statistical methods indicated that there were no detectable differences (P greater than .05) in flavor between broilers fed the anticoccidial agent in the diet and those fed the control diet.

Comparison of the antimycoplasma activity of two commercially available tylosin premixes.

Two tylosin premixes (referred to in this report as Premix A and tylosin Premix B), obtained as commercial products from Japan, were analyzed microbiologically for tylosin and by high pressure liquid chromatography (HPLC) for macrolide content. They were evaluated in the feed at concentrations of 550 and 1100 ppm antibiotic activity for the treatment of chickens with induced Mycoplasma gallisepticum (MG) infection. The tylosin microbiological assay value for Premix A was 3.0% below and for Premix B, 7.5% above the tylosin concentration stated on the respective premix labels. Analyses by HPLC showed tylosin Premix A contained 84% tylosin and 16% other macrolide derivatives; whereas, tylosin Premix B contained 42.6% tylosin, 46.6% other macrolides, and 10.8% unidentified material. When the two premixes were administered in the feed for 5 days as treatments for MG-infected chickens, tylosin Premix A was significantly more effective than tylosin Premix B, as measured by reductions in mortality, air sac lesions, and infection as indicated by development of MG antibody. In experiments in pigs where individual macrolide derivatives were used, tylosin was more effective than the other macrolides, desmycosin or macrocin, for the treatment of Mycoplasma hyopneumoniae infection. It is apparent from these studies that commercially available tylosin products may contain varying quantities of tylosin and related macrolide antibiotics and that these differences may significantly affect the efficacy of the products.

Effects of feeding tylosin to layers exposed to Mycoplasma gallisepitcum.

Two experiments are reported in which the effect of tylosin upon the development of Mycoplasma gallisepticum (MG) infection in replacement layers was monitored by serological and cultural methods. Concentrations of tylosin tested included 0, 22, 38.5, and 55 ppm. Egg production and feed consumption data were collected for one year. Tylosin slowed the rate of spread of MG infection as measured by serological and cultural methods. The effect of tylosin on the spread of MG infection was dose related. Hen day egg production peaked at 85 to 87% in the mediated groups, while controls peaked at 81 to 84%. The magnitude of tylosin effect on production increased with time to a maximum difference of 10 to 12% at 52 weeks. Feed efficiency was markedly improved by all concentration of tylosin ranging from 5% at peak production to 12 to 18% at 52 weeks. The incidence of shell-less or soft shelled eggs was markedly reduced in the tylosin treated group.