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.     

A comparison of prophylactic efficacy of tilmicosin and a new formulation of oxytetracycline in feedlot calves

Two replicated-pen field studies were performed under commercial feedlot conditions in western Canada to compare the administration of long-acting oxytetracycline at 30 mg/kg body weight (BW) versus tilmicosin at 10 mg/kg BW to feedlot calves upon arrival at the feedlot. Ten thousand nine hundred and eighty-nine, recently weaned, auction market derived, crossbred beef steer and bull calves were randomly allocated upon arrival at the feedlot to one of 2 experimental groups as follows: oxytetracycline, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at a rate of 30 mg/kg BW; or tilmicosin, which received subcutaneous tilmicosin (300 mg/mL formulation) at a rate of 10 mg/kg BW. There were 20 pens in each experimental group. In Study 1 and in the combined analysis, the initial undifferentiated fever (UF) treatment rate was significantly (P < 0.05) higher in the oxytetracycline group as compared with the tilmicosin group. There were no significant (P > or = 0.05) differences in first UF relapse, second UF relapse, third UF relapse, overall chronicity, overall rail, overall mortality, bovine respiratory disease (BRD) mortality, hemophilosis mortality, arthritis mortality, or miscellaneous mortality rates between the experimental groups in either study or in the combined analysis. In addition, there were no significant (P > or = 0.05) differences in initial weight, final weight, weight gain, days on feed, daily dry matter intake, average daily gain, or the dry matter intake to gain ratio between the experimental groups in either study or in the combined analyses. In the economic analysis, there was a net economic advantage of $5.22 CDN per animal in the oxytetracycline group, due to a lower prophylactic cost, even though the UF therapeutic cost was higher.     

A comparative study on irritation and residue aspects of five oxytetracycline formulations administered intramuscularly to calves, pigs and sheep

After intramuscular (IM) administration (dose 20 mg/kg) of three 20% (Terramycin/LA (product A), Alamycin LA (product B) and Terralon 20% LA (product C) and two 10% oxytetracycline (OTC) formulations (Engemycin 10% (product D) and Oxyject 10% (product E)), to calves, pigs and sheep, the OTC residue concentrations were determined in organs, muscle, fat, plasma, urine and at the injection sites at 10 days post injection (p.i.). At that time the irritation at the injection site was studied, too. The three 20%-formulations (products A, B, C) and one 10%-formulation (product E) induced considerable local irritation in and between the muscles. This was most pronounced in calves and pigs; in sheep the extent of irritation was limited. Ten days after administration of formulations A, B, C and E, OTC residues were found in organs and the OTC recovery at the injection sites varied widely among the three species. Following IM injection of product D minimal tissue irritation and no OTC residues could be detected at the injection site at 10 days p.i. The differences in local tissue irritation and the residue state of the carcass (including injection site) are related to the various solvent systems used in the formulations.     

Effect of a new macrolide antibiotic (tilmicosin) on pneumonia experimentally induced in calves by Mycoplasma bovis and Pasteurella haemolytica

Two gnotobiotic calves were treated once with tilmicosin (20 mg kg-1) six hours before they were infected by the intratracheal route with Mycoplasma bovis and Pasteurella haemolytica serotype 1. This treatment prevented colonisation of the lungs by P haemolytica and considerably reduced colonisation by M bovis, and the clinical scores and the extent of pneumonic consolidation, compared with two untreated gnotobiotic calves, both of which had to be killed in extremis for humanitarian reasons within 24 hours of infection. In a second experiment, 10 conventionally reared calves were similarly exposed to infection and, at the onset of clinical disease, five were treated once with tilmicosin (20 mg kg-1). Colonisation by P haemolytica and M bovis, the clinical scores and extent of pneumonic consolidation were suppressed or greatly reduced in the treated compared with the untreated calves, one of which had to be killed in extremis two days after infection. It was concluded that tilmicosin had a beneficial effect.     

Randomized field trial comparing the efficacy of florfenicol and oxytetracycline in a natural outbreak of calf pneumonia using lung reaeration as a cure criterion

BackgroundRespiratory infections are the main indication for antimicrobial use in calves. Optimal treatment duration currently is unknown, but shorter duration would likely decrease selection for antimicrobial resistance.Hypothesis/ObjectivesDetermine differences in cure rate and healing time between animals treated with florfenicol and oxytetracycline in a natural outbreak of respiratory disease using reaeration observed on thoracic ultrasound examination as healing criterion.AnimalsCommercial farm housing 130, 3 to 9 month old Belgian blue beef calves.MethodsRandomized clinical trial during an outbreak of respiratory disease. Metaphylactic treatment was initiated, randomly treating animals with either florfenicol or oxytetracycline. Ultrasonographic follow‐up was done the first day and every other day for a 14‐day period. At the individual animal level, treatment was discontinued when reaeration of the lungs occurred. Differences in cure rate and healing time were determined.ResultsOf the 130 animals studied, 67.7% developed a lung consolidation ≥0.5 cm. The mean ultrasonographic healing time was 2.5 days in the florfenicol group compared to 3.1 days in the oxytetracycline group (P = .04). After single treatment, 80.6% and 60.3% had no consolidations in the florfenicol and oxytetracycline groups, respectively (P = .01). A Mycoplasma bovis strain was genetically and phenotypically determined to be susceptible to both antimicrobials.Conclusions and Clinical ImportanceUltrasonographic lung reaeration shows potential as a cure criterion to rationalize antimicrobial use for outbreaks of pneumonia. In our study, florfenicol resulted in a faster cure and higher reduction in antimicrobial usage than did oxytetracycline.     

Long-acting oxytetracycline for control of induced Pasteurella multocida rhinitis in swine

A long-acting oxytetracycline formulation was evaluated for control of rhinitis induced experimentally in pigs with a capsular type A, toxin-negative, low-passage strain of Pasteurella multocida. The pigs were 6 to 7 weeks old and were naturally infected with Haemophilus parasuis. The H parasuis infection was thought to predispose to establishment of P multocida in the nasal cavity. A long-acting oxytetracycline formulation was given IM at the rate of 20 mg/kg, 4 times at 5-day intervals. Medication reduced (P less than 0.05) the severity of turbinate atrophy and the proportion of pigs with P multocida and H parasuis in their nasal cavities. Numbers of colonies of P multocida and H parasuis isolated were also less in medicated pigs.     

Relative efficacy of two oxytetracycline formulations and doxycycline in the treatment of acute anaplasmosis in splenectomized calves

The efficacy of 3 antibiotic formulations was measured in the treatment of artificially induced anaplasmosis in the early stages of an ascending parasitemia (1% to 4%) in 23 splenectomized calves. Group 1, consisting of 5 calves, served as nontreated controls. Four calves (group 2) were treated 1 time with 10 mg of oxytetracycline (T-50)/kg of body weight IM; 5 calves (group 3) were treated 3 times with 10 mg of T-50/kg IM; 5 calves (group 4) were treated 1 time with 20 mg of an experimental oxytetracycline (T-200)/kg IM; and 4 calves (group 5) were treated 1 time with 10 mg of a synthetically derived antibacterial agent, doxycycline (D-100)/kg IM. All control calves died and 1 of 4 calves died that was treated 1 time with T-50. Other deaths did not occur. All treatments were effective in moderating the infective process, but T-50 given 3 times and T-200 given 1 time were markedly more effective than T-50 and D-100 given 1 time. There appeared to be little or no difference in therapeutic efficacy between T-50 and D-100 given 1 time and between T-50 given 3 times and T-200 given 1 time.     

The effect of streptomycin, oxytetracycline, tilmicosin and phenylbutazone on spermatogenesis in bulls

To determine whether declining semen quality associated with health problems may be due to certain antibiotic or anti-inflammatory treatments, semen was collected 3 times per week for up to 42 d from 6 normal bulls after treatment with oxytetracycline, tilmicosin, dihydrostreptomycin, or phenylbutazone. No adverse effects on semen quality were observed.     

A comparative study of two antimicrobial/anti-inflammatory formulations in the treatment of canine otitis externa

The efficacy and tolerability of a marbofloxacin-clotrimazole-dexamethasone otic suspension (MCD) was compared with a standard topical treatment using a phase III clinical trial protocol. In a total of 140 dogs with clinical signs of acute or subacute otitis externa, Staphylococcus, Pseudomonas, Enterobacteriaceae and Malassezia were isolated from samples taken at inclusion to identify the causative pathogen; a further sample was collected in the event of failure or relapse, and from dogs (at day 14) for which Pseudomonas species had been isolated at inclusion. One group received MCD (10 drops per affected ear) once daily and a second received Surolan (containing polymyxin B, miconazole and prednisolone) (5 drops per affected ear), twice daily. Each group received treatment for 7 or 14 days according to the clinical outcome on day 7. Efficacy and tolerability were evaluated on days 7, 14 and, if necessary, 28 for dogs treated for 14 days. The trial demonstrated equivalence of both treatments in terms of efficacy, with a cure rate of 58.3% for MCD and 41.2% for Surolan. Both medications were equally well tolerated by dogs, but MCD was superior in terms of pain relief, decrease in pus quantity and smell, response rate and investigator's assessment on day 14.     

Chronic pneumonia and polyarthritis syndrome in a feedlot calf

A feedlot heifer was diagnosed with chronic pneumonia and polyarthritis syndrome (CPPS), which was confirmed on postmortem examination. The syndrome is caused by Mycoplasma bovis; however, available data support the theory that other pathogens play a role in predisposing to this disease. Continued research on CPPS focuses on pathogenesis, treatment, and prevention.     

Comparison between the minimal inhibitory concentration of tilmicosin and oxytetracycline for bovine pneumonic pasteurella haemolytica isolates

Summary

The minimal inhititory concentration (MIC) of tilmicosin and oxytetracycline was dertermined for Pasteurella haemolytica isolated from Dutch cattle in 1991. The agar dilution method was used. Of the Pasteurella haemolytica strains examined, 96% (24) had a MIC for tilmicosin of 2 μg/ml or lower; in one strain the MIC was 8 μg/ml. The MIC for oxytetracycline was equal to or higher than 64 μg/ml in 19 strains (76%), whereas for 5 strains the MIC was 1 μg/ml and for 1 strain 2 μg/ml.     

A clinical comparison of two injectable oxytetracycline preparations for the treatment of pneumonia in calves

Summary

The experiment was set up to make a clinical comparison in 140 pneumonic calves of two injectablc oxytetracycline formulations with different pharmacokinetic properties: Engcmycin^® 10% DD and Terramycin^® LA. The animals were examined clinically on the day of admission (day 0) and 1,2,3, 6 and 21 days thereafter. Calves were treated on day 0 with either Engemycin^® 10% DD (n=70) or Terramycin^® LA (n=70) at a dose of 20 mg/kg. If animals were not cured after one single injection, a second or even third injection was given at day 3 and day 6 respectively. No significant differences between the two treatment groups were found with regard to the number of injections needed for a complete cure, the evolution of dyspnoea, or the restoration of appetite. Thus both preparations gave comparable recovery rates. A difference between the two groups existed in the evolution of body temperature during the test period: the return to a normal body temperature occured more rapidly in the Engemycin^® 10% DD group. Regarding the tolerance aspects the degree of irritation depended in the preparation used. Calves treated with Engemycin^® 10% DD showed significantly less swelling of the injection site on day 1 then calves treated with Terramycin^® LA.     

On the aetiopathogenesis of Mycoplasma pneumonia in calf

A pure culture of Mycoplasma (M.) bovis was isolated from calves with respiratory disease, exhibiting the picture of lymphohistiocytic proliferative pneumonia with presence of eosinophil plasmatic cells. A mixed infection of M. bovis and Pasteurella (P.) multocida was demonstrated in calves with exudative pneumonia. Both M. bovis and Haemophilus (H.) somnus were recovered from calves with necrotic pneumonia. All 3 organisms--M. bovis, P. multocida, and H. somnus--were present in cases of exudative-necrotic pneumonia. It was also shown that M. bovis played a primary role in the aetiopathogenesis of respiratory diseases caused by mixed infections.     

Comparison of the pharmacokinetics and local tolerance of three injectable oxytetracycline formulations in pigs

The pharmacokinetic properties and local tolerance of three oxytetracycline formulations, one conventional (Engemycine, 10%) and two long-acting (Oxyter LA, 20% and Terramycin LA, 20%) were compared in clinically healthy cross-bred pigs following intramuscular injection of single doses (20 mg/kg body weight) in the neck region. Non-compartmental methods were used to calculate the pharmacokinetic parameters. Assessment of local tolerance was based on serum creatine phosphokinase (CPK) concentration and a combination of echographical, macroscopic and histological examinations of the intramuscular injection site. Statistically significant differences (one-way analysis of variance, F-test) were obtained between the three formulations in peak plasma concentration, peak time and mean residence time. Area under the curve did not differ significantly between the formulations. Using the Students t-test for paired data, the two long-acting formulations differed significantly in peak plasma concentration and peak time. Both of the long-acting formulations differed significantly from the conventional formulation in the peak time and mean residence time. All three formulations produced an increase in serum CPK concentrations. The increase in CPK concentration was present from 6 to 24 h post treatment for Terramycin LA, from 6 to 72 h for Oxyter LA and from 6 to 96 h for Engemycine (the conventional formulation). Echographical examination of the injection site showed lesions of an inflammatory type up to 96 h after IM injection of the drug products, whereas from 7 days the lesions represented primarily scar formation. Histological examination of tissue from the injection site did not correlate with echographical scores. The results obtained in this study show that the long-acting formulations provide significantly longer mean residence times of oxytetracycline than the conventional formulation, and that local tolerance at the IM injection site was similar for all three formulations under the experimental conditions used in this study. It can be concluded that the longacting formulations provide the advantage of a longer dosage interval when administered to pigs by intramuscular injection in the neck region at a dose of 20 mg/kg body weight.     

口服不同剂型替米考星在鸡体内相对生物等效性研究

本试验按单剂量口服的方法对健康蛋鸡进行替米考星可溶性粉和替米考星溶液中主要组分替米考星的生物利用度和药代动力学研究。利用HPLC方法分析不同时间点试验鸡血浆中的药物浓度。药物的药动学参数结果显示,替米考星可溶性粉和替米考星溶液的平均血药浓度-时间曲线下面积(AUC0-48)分别为(16.947±0.624)μg/mL.h和(16.020±0.631)μg/mL.h,没有显著差异;二者AUC0-48比值为1.058,Cmax分别为(0.759±0.012)μg/mL和(0.764±0.012)μg/mL,比值为0.993;替米考星可溶性粉和替米考星溶液的t1/2β、C l(s)、t1/2 Ka和V/F(c)均没有显著差异;二者的tmax分别为(1.211±0.036)h和(1.030±0.063)h虽然有显著差异,但并不能以此说明二者生物学的非等效性。试验结果说明,单剂量口服替米考星可溶性粉和替米考星溶液后,替米考星被迅速吸收,消退缓慢,依据生物等效性的重要评判指标,得出替米考星可溶性粉和替米考星溶液在治疗中可以相互替代。