Effect of tiamulin administered by various methods and dosages on turkeys at different ages

Healthy male turkeys not receiving monensin in their feed were treated with tiamulin by various methods and at different ages. Nine cycles of treatments were performed at the ages of 26, 40, 61, 89, 103, 117, 131, 145, and 160 days. Intramuscular of subcutaneous injections of 12.5 mg/kg tiamulin up to 145 days did not result in any signs of toxicity or impair growth rate. Administration at a dose of up to 25 mg/kg, using the drinking-water-deprivation technique, caused no effect in turkeys up to 160 days (marketing age).     

Monensin toxicosis in swine: potentiation by tiamulin administration and ameliorative effect of treatment with selenium and/or vitamin E

Modulation of acute monensin toxicosis in swine was evaluated in 2 studies. In study 1, 56 weanling male pigs were allotted to 14 groups of 4 each. Pigs in 7 groups were given tiamulin in the drinking water (to supply 7.7 mg/kg of body weight/day) for 3 days before and for 2 days after monensin administration. Monensin was given as a single oral dose (at 0, 7.5, 15, 25, 50, 75, or 100 mg/kg) to pigs in groups with or without tiamulin exposure. Prominent acute clinical signs of monensin toxicosis (hypermetria, hind limb ataxia, paresis, knuckling of hind limbs, and recumbency) developed by 2 to 6 hours after dosing in pigs given 15 or 25 mg of monensin/kg with tiamulin exposure, but not in pigs given the 15 or 25 mg of monensin/kg without tiamulin exposure. Also, the extent of monensin-induced skeletal muscle damage at 4 days after monensin dosing was enhanced in pigs given 7.5, 15, or 25 mg of monensin/kg and exposed to tiamulin. In study 2, 48 weanling male pigs were allotted to 8 groups of 6 each. Four groups of pigs were given 20 mg of monensin/kg orally, and 4 groups were given 100 mg of monensin/kg orally. For each monensin dose, a group was treated 24 hours before monensin administration with (i) selenium (Se)-vitamin E preparation, 0.25 mg of Se and 68 IU of d-alpha-tocopheryl acetate (vitamin E)/kg, IM; (ii) vitamin E only, 68 IU of d-alpha-tocopheryl acetate/kg; (iii) Se only, 0.25 mg of Se/kg; or (iv) vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on the toxic interaction between monensin and tiamulin in rats: effects on P450 activities

Studies were carried out to investigate the effects of monensin and tiamulin, and the simultaneous administration of both compounds on microsomal enzymes in rats. In Phase I of the experiments the effects of monensin and tiamulin were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 120, and 200 mg/kg body weight, respectively), while in Phase II the two compounds were administered simultaneously (monesin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively). When monensin was administered by itself, it exerted no significant effect on microsomal liver enzymes. In a few cases, slight inhibition of certain enzyme activities was seen. Tiamulin provoked a dose-dependent hepatic enzyme induction. The combined administration of monensin and tiamulin at low doses (10 and 40 mg/kg, respectively) resulted in marked elevation of P450-related enzyme activities. The enzyme induction was more pronounced in females than in males. The results suggest that the simultaneous administration of tiamulin may influence the biotransformation of monensin, possibly increasing the amount of reactive metabolite(s) of the ionophore antibiotic.     

Studies on the toxic interaction between monensin and tiamulin in rats: toxicity and pathology

The characteristics of the toxic interaction between monensin and tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin and tiamulin were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 120, and 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 and 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined administration, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect and vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous administration of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium and vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the administration of 50 mg/kg monensin alone.     

Safety of lasalocid in turkeys and its compatibility with tiamulin

An investigation involving 640 turkeys demonstrated that the inclusion of lasalocid continuously from day-old to 16 weeks of age, at levels up to 375 ppm in the feed, produced no adverse effects; furthermore, the inclusion of 125 ppm lasalocid in the feed was compatible with the administration of 250 ppm tiamulin in the drinking water continuously for five days to turkeys over the same age range.     

Interaction of ionophore and vitamin E in knockdown syndrome of turkeys

Monensin and vitamin E concentrations, as well as histopathology of skeletal muscles and myocardium, were evaluated in broad-breasted white turkeys kept in commercial facilities. Turkeys with knockdown syndrome had myopathy of skeletal muscles, but no lesions in the myocardium. Generally, concentration of monensin in serum was highest in turkeys diagnosed with knockdown syndrome given more than 90 mg/kg of monensin in the diet, followed by turkeys diagnosed with knockdown syndrome given <90 mg/kg of monensin in the diet, healthy turkeys fed a diet that contained <90 mg/kg of monensin, and finally healthy turkeys fed a diet free of monensin (not detectable). However, the concentration of monensin was highly variable within each group, and the median was lower than the average. Vitamin E concentrations in the livers varied from low-normal to below normal and were statistically higher in healthy turkeys fed a diet free of monensin than in the livers of birds from the 3 groups exposed to monensin. This suggests that the concentration of monensin in serum positively correlates to the severity of clinical signs and pathology and to the amount of monensin in the feed. Although the methodology developed to detect serum monensin concentrations is beneficial and accurate for case investigations, it is recommended that several samples from each flock be evaluated because of variation within a flock. The current study also suggests that monensin in the feed could induce lower concentrations of vitamin E in the liver of turkeys and can predispose the turkeys to knockdown syndrome.     

Chronic effects of moniliformin in broiler and turkeys fed dietary treatments to market age

Floor pen studies were conducted, with broilers from 1 to 7 wk of age and with turkeys from 1 to 14 wk of age, to evaluate the chronic effects of moniliformin (M). Fusarium fujikuroi (M-1214) culture material was added to typical corn-soybean basal diets to supply 0, 25, or 50 mg M/kg diet (broilers) or 0, 12.5, 25, 37.5, or 50 mg M/kg diet (turkeys). Compared with controls, chicks fed diets containing 50 mg M/kg consumed more feed, had lower body weight gain, were less efficient in converting feed to body weight gain, and had increased relative heart and proventriculus weights. Chicks fed the diet containing 50 mg M/kg also had significantly higher mortality and decreased mean corpuscular volumes compared with controls. Broilers fed 25 and 50 mg M/kg also had increased serum gamma glutamyltransferase activities. Feed intake, body weight gain, and feed conversion of turkeys fed dietary M were not affected. At 6 and 14 wk, turkeys fed 25, 37.5, or 50 mg M/kg diet had increased (P < 0.05) relative heart weights when compared with controls. At week 14, turkeys fed diets containing 37.5 or 50 mg M/kg also had increased (P < 0.05) relative liver weights compared with turkeys fed 0, 12.5, or 25 mg M/kg diet. Lesions, observed only in the hearts of broilers and turkeys fed 50 mg M/kg, were loss of cardiomyocyte cross striations, increased cardiomyocyte nuclear size, and an increased number of cardiomyocyte mitotic figures (turkeys only). Results indicate that > or = 37.5 mg M/kg is hepatoxic and > or = 25 mg M/kg is cardiotoxic to turkeys and 50 mg M/kg diet is toxic to broilers fed to market age.     

Comparison of the oral bioavailability and tissue disposition of monensin and salinomycin in chickens and turkeys

Henri, J., Maurice, R., Postollec, G., Dubreil‐Cheneau, E., Roudaut, B., Laurentie, M., Sanders, P. Comparison of the oral bioavailability and tissue disposition of monensin and salinomycin in chickens and turkeys. J. Vet. Pharmacol. Therap.  35 , 73–81. The current study describes the pharmacokinetic parameters of two carboxylic polyether ionophores: monensin in turkeys and salinomycin in chickens. These data can be used to understand and predict the occurrence of undesirable residues of coccidiostats in edible tissues of these animal species. Special attention is paid to the distribution of residues between the different edible tissues during and at the end of the treatment period. For the bioavailability studies, monensin was administered to turkeys intravenously, in the left wing vein, at a dose of 0.4 mg /kg and orally at a dose of 20 mg /kg. Salinomycin was administered to chickens intravenously, in the left wing vein, at a dose of 0.25 mg /kg and orally at a dose of 2.5 mg /kg. Residue studies were carried out with supplemented feed at the rate of 100 mg /kg of feed for monensin in turkeys and 70 mg /kg for salinomycin in chickens, respectively. Coccidiostats had a low bioavailability in poultry (around 30% for monensin in chickens, around 1% for monensin in turkeys and around 15% for salinomycin in chickens). Monensin in chickens had a longer terminal half‐life (between 3.07 and 5.55 h) than both monensin in turkeys (between 1.36 and 1.55 h) and salinomycin in chickens (between 1.33 and 1.79 h). The tissue /plasma partition coefficients showed a higher affinity of both monensin and salinomycin for fat, followed by liver and muscle tissue. The depletion data showed a fairly rapid elimination of coccidiostats in all the tissues after cessation of treatment. According to the results of depletion studies, a withdrawal period of 1 day seems sufficient to avoid undesirable exposure of consumers.     

Oocyst Discharge, Rumen Metabolism and Performance of Early Weaned Lambs with Naturally Occurring Coccidiosis Fed Monensin

Ninety-six 9.5 kg early-weaned lambs with naturally occurring coccidiosis were fed monensin either at 0, 11, 22, or 33 mg/kg of feed for 105 days. Fecal oocyst discharge during the first three days was highest with monensin 22 mg, lowest with monensin 33 mg and averaged 149.6 × 10³ oocysts per gram feces for all lambs. Monensin at 22 mg/kg of feed reduced Eimeria ninakohlyakimovae and E. ahsata oocyst discharge.

Organic matter and crude protein digestibilities were highest (P ≤ 0.05) in lambs fed monensin 22 mg/kg of feed. Monensin increased (P ≤ 0.01) rumen ammonia and propionic acid and decreased (P ≤ 0.01) acetic acid. Feeding monensin 33 mg decreased (P ≤ 0.05) feed intake by 5% and had no effect on gain or feed efficiency. Optimal responses were observed with monensin at 11 mg, feed consumption was not affected, gains were 8% higher (P ≤ 0.05) and feed was utilized 9% more efficiently (P ≤ 0.05) than the controls. In conclusion, monensin was an effective therapeutic agent against naturally occurring coccidial infections in early weaned lambs. Performance responses were largest with monensin fed at the rate of 11 mg/kg of feed.

     

Eradication of some infectious pig diseases by perinatal tiamulin treatment and early weaning

From 10 days before the expected date of farrowing onwards, 97 sows infected by Mycoplasma hyopneumoniae and Treponema hyodysenteriae were given tiamulin daily at a dosage of 20 mg/kg bodyweight via the feed. Three days before farrowing the sows were washed with a disinfectant and transferred to an isolated farrowing house. The sucking piglets remained with their dams for five days, during which time the sows continued to receive the tiamulin-containing feed. The sucking piglets also received tiamulin daily at a dosage of 30 mg/kg bodyweight. At six days old the weaker piglets of the litter were returned to the original herd, together with their dams. A total of 574 piglets of about 1.5 kg bodyweight each were transferred to an isolated and previously disinfected pig farm and reared there. A total of 13.8 per cent of these pigs died by 50 days old. On the isolated farm, 10.9 per cent of the 829 second generation piglets born to the 101 first generation sows, died up to the age of 50 days. On the isolated farm about 2000 pigs were subjected to repeated clinical, pathological and laboratory examinations for M hyopneumoniae, T hyodysenteriae, Aujeszky's disease virus and Leptospira species during the three year period of study. No evidence of infection with any of these agents was found in the 2000 pigs of the isolation herd, although the original sow herd had been latently infected by these pathogens. No maternally derived antibodies against these pathogens were detectable in sera of three-day-old sucking piglets of the second and third generations.     

Animal nutrition for veterinarians--recent cases of clinical disorders in horses after intake of ionophore-containing feed

Anamnesis and clinical signs of horses form five different stables after ingestion of ionophores are reported and techniques of feed examination are described. Within a few hours or days after feeding of new types or batches of concentrates horses fell ill. They showed colic-like symptoms with intense sweating and ataxia. Most of the sick animals died within a short time span. Samples of the concentrates were analysed and different types and amounts of ionophores were detected. In four cases contamination by monensin in concentrations of less than 5 mg to 679 mg/kg feed were found. One feed sample contained monensin (8.8 mg/kg feed) as well as salinomycin (67.3 mg/kg feed). In one case lasalocid (7.9 mg/kg feed) was present. One horse from the stable where animals had obtained concentrates containing monensin (679 mg/kg feed) was necropsied. Typical signs of monensin intoxication with severe myocardial degeneration were found. Veterinarians should be alert to this rare but severe intoxication of horses.     

Pharmacokinetics and relative bioavailability of tiamulin in broiler chicken as influenced by different routes of administration

The bioavailability and pharmacokinetic disposition of tiamulin in broiler chicken were investigated after administration through the crop, drinking water, and feed at 40 mg/kg body weight. Residues of tiamulin in tissues of broiler chicken were also assessed. Plasma and tissue concentrations of tiamulin were analyzed by reverse‐phase high‐performance liquid chromatography (HPLC) method. Plasma concentration–time data were described by the non‐compartmental model for all three routes, and pharmacokinetic parameters were calculated. There were no significant differences (p > 0.05) in pharmacokinetic parameters and mean plasma concentrations of tiamulin between three routes tested (crop, water, and feed), indicating equal efficacy. Tiamulin residues in edible tissues (muscles, skin, and fat) were lower than the advocated maximum residue limit (MRL of 0.1 µg/g and that of liver was 1 µg/g) on the 3rd day. No traces were found on the 5th day after drug administration. This indicated that the withdrawal period (less than 5 days) is very short, which makes it safer. This study shows that tiamulin can be used with equal efficacy through all routes of administration in broiler chicken (crop, water, and feed).     

Simultaneous treatment of chickens with salinomycin and tiamulin in feed.

Laboratory and field experiments involving more than 100,000 birds were performed to assess the effect of simultaneous in-feed medication of chickens with salinomycin and tiamulin at various concentrations. In an artificial infection study with Mycoplasma gallisepticum, low levels of tiamulin (10-40 ppm) did not induce signs of ionophore intoxication with salinomycin at 60 ppm in the feed, whereas levels of 50 ppm caused early signs with a mild growth depression. A level of 20 ppm gave a maximum average improvement in growth rate of 12.5%. There was a dose-related response in mycoplasma lesion inhibition, with 50 ppm reducing lesions by 75%. In the two field trials, chickens suffering from mycoplasmosis complicated with infectious bronchitis and receiving 60 ppm salinomycin in the feed showed marked improvements in mortality rates, lesion scores, and feed-conversion efficiency when tiamulin was added at 20 ppm and 30 ppm in the feed. There were no signs of incompatibility between the two antibiotics at these levels.     

Performance of feedlot steers fed diets containing laidlomycin propionate or monensin plus tylosin, and effects of laidlomycin propionate concentration on intake patterns and ruminal fermentation in beef steers during adaptation to a high-concentrate diet.

Two hundred eighty-eight beef steers (British x Continental x Brahman) were fed a 90% concentrate diet containing either no ionophore (control), laidlomycin propionate at either 6 or 12 mg/kg of dietary DM, or monensin plus tylosin (31 and 12 mg/kg of DM, respectively). Neither of the two levels of laidlomycin propionate nor monensin plus tylosin affected (P greater than .10) ADG or feed:gain ratio. Monensin plus tylosin reduced (P less than .01) daily DMI for the 161-d trial period compared with the other three treatments. Laidlomycin propionate at 6 mg/kg increased (P less than .05) DMI relative to the control, laidlomycin propionate at 12 mg/kg, and monensin plus tylosin diets during the 2nd wk of the trial and from d 57 to 84. Treatments did not affect carcass measurements. In a second experiment, 12 ruminally cannulated steers were fed diets containing no ionophore or laidlomycin propionate at either 6 or 12 mg/kg of DM. Samples were obtained for two consecutive days while the dietary concentrate level was 75%, after which the diet was switched abruptly to 90% concentrate, and samples were collected on several days during a 21-d period. The rate at which steers consumed their daily allotment of feed was not altered markedly by laidlomycin propionate. Likewise, laidlomycin propionate did not affect total ruminal VFA concentrations or proportions. Ruminal concentrations of D-lactate were reduced (P less than .10) by 6 but not by 12 mg/kg of laidlomycin propionate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute poisoning in turkeys caused by incompatibility of monensin and tiamulin

The incompatibility of the anticoccidial monensin and the antibiotic tiamulin when administered simultaneously to chickens is well documented. Signs similar to monensin poisoning have been seen in turkeys given these two drugs together in field cases. This work describes a preliminary trial in which simultaneous administration of therapeutic doses resulted in acute severe poisoning with a high mortality.     

Serum,milk, and tissue monensin concentrations in cattle with adequate and potentially toxic dietary levels of monensin: pharmacokinetics and diagnostic interpretation

Used in both beef cattle and dairy cows, monensin can provide many health benefits but can, when unintended overexposures occur, result in adverse effects. Information on serum and tissue concentrations following overexposure and/or overt toxicosis which may aid in diagnostics and clinical outcome is lacking. The aim of this study was to determine concentrations of monensin in biological specimens following oral exposure for 10 days to an approved dose (1 mg/kg) and a higher dose (5 mg/kg) of monensin given daily on a body weight basis to 10 dairy cows. No deaths were reported; cows receiving 5 mg/kg showed early signs of toxicosis including depression, decreased feed intake, and diarrhea after 4 days of exposure. Histopathological findings were minimal in most cows. Pharmacokinetic modeling of the detected serum concentrations for the 1 and 5 mg/kg dose groups determined the C_max, T_max, and t_1/2λ to be 0.87 and 1.68 ng/mL, 2.0 and 1.0 h, and 1.76 and 2.32 days, respectively. Mixed regression models showed that the dose level and days since last dose were significantly associated with monensin concentrations in all four tissues, and with cardiac troponin levels. The high dose resulted in a significant elevation of monensin in tissues at approximately 4.7 times compared to the monensin concentrations in the tissues of animals from the low‐dose group. The cTnI concentrations in the high‐dose group were 2.1 times that of cTnI in the low‐dose group. Thus, the ability to diagnose monensin overexposure and/or toxicosis will improve from knowledge of biological monensin concentrations from this study.     

马杜霉素和泰妙菌素联合应用对雏鸡新城疫抗体水平的影响

试验将不同剂量的马杜霉素和泰妙菌素分别添加到雏鸡的饲料和饮水中同时使用,通过检测不同组别雏鸡血清中ND血凝抑制效价,探讨马杜霉素和泰妙菌素不同剂量联合应用时对雏鸡免疫功能的影响。试验结果表明:正常推荐剂量的马杜霉素5mg/kg与泰妙菌素10mg/kg联合使用时,一般不会对机体免疫造成明显伤害;应用马杜霉素10mg/kg拌料能明显造成机体免疫系统伤害,当其与正常或加倍剂量的泰妙菌素联合应用更会加重对机体免疫功能的不良影响,致使抗体水平下降。     

Performance, methanogenesis and nitrogen metabolism of finishing steers fed monensin and nickel

Sixty-four Angus steers initially averaging 354 kg were allotted to a 2 X 2 factorial arrangement of treatments to determine the effects of dietary Ni (0 or 5 mg/kg supplemental), monensin (0 or 33 mg/kg) and their possible interaction on performance, methane production and N metabolism. The basal diet was a high energy, corn-cottonseed hull based diet containing 10.2% crude protein and .30 mg/kg Ni on a dry matter basis. Monensin reduced (P less than .05) feed intake, did not affect average daily gain and improved (P less than .05) feed conversion over the 102-d study. Nickel supplementation did not significantly alter or interact with monensin to affect steer performance. However, steers fed Ni tended to have higher average daily gains and improved feed conversions. Monensin decreased (P less than .05) in vitro methane production, altered several carcass traits, increased (P less than .05) molar proportion of ruminal propionate and decreased (P less than .05) molar proportion of ruminal acetate. Nickel did not alter methane production, carcass characteristics or ruminal volatile fatty acid proportions. Both monensin and Ni increased (P less than .05) ruminal fluid urease activity when samples were obtained before feeding. A significant monensin X Ni interaction was found to affect ruminal epithelial urease activity. Monensin increased ruminal epithelial urease in steers not receiving supplemental Ni, but had no effect on ruminal epithelial urease activity in steers fed supplemental Ni. Ruminal fluid protein and ammonia-N were decreased (P less than .05) by monensin. Results of this study indicate that Ni may interact with monensin to affect ruminal epithelial urease activity but not performance or methane production in finishing steers.     

Milk residues and performance of lactating dairy cows administered high doses of monensin

Milk residues and performance were evaluated in lactating cows that were fed up to 10 times the recommended dose of monensin. Following an acclimatization period of 14 d, during which cows were fed a standard lactating cow total mixed ration containing 24 ppm monensin, 18 lactating Holstein dairy cows were grouped according to the level of feed intake and then randomly assigned within each group to 1 of 3 challenge rations delivering 72, 144, and 240 ppm monensin. Outcome measurements included individual cow daily feed intakes, daily milk production, body weights, and monensin residues in composite milk samples from each cow. There were no detectable monensin residues (< 0.005 microg/mL) in any of the milk samples collected. Lactating cows receiving a dose of 72 ppm monensin exhibited up to a 20% reduction in dry matter intake, and a 5% to 15% drop in milk production from the pre-challenge period. Cows receiving doses of 144 and 240 ppm monensin exhibited rapid decreases in feed intake of up to 50% by the 2nd d and milk production losses of up to 20% and 30%, respectively, within 4 d. Lactating cows receiving up to 4865 mg monensin per day had no detectable monensin residues (< 0.005 microg/mL) in any of the milk samples collected. Results of this study confirm that food products derived from lactating dairy cattle receiving monensin at recommended levels are safe for human consumption.     

Comparative feeding value of supplemental fat in finishing diets for feedlot steers supplemented with and without monensin

Two comparative slaughter trials and a metabolism trial were conducted. Treatments consisted of: 1) 0 fat, 0 monensin; 2) 4% yellow grease, 0 monensin; 3) 0 fat, 33 mg/kg monensin and 4) 4% yellow grease, 33 mg/kg monensin. Trial 1 involved 104 crossbred beef steers (267 kg) in a 140-d comparative slaughter trial. There were no interactions (P greater than .20) between supplemental fat and monensin on steer performance. Monensin supplementation decreased rate of weight gain (P less than .10) and feed intake (P less than .05) with no effect on energy value of the diet (P greater than .20). Fat supplementation increased (P less than .01) rate of weight gain 12.5% and increased the net energy for maintenance (NEm) and net energy for gain (NEg) value of the diet 8.5 and 9.4%, respectively. Trial 2 involved 154 Holstein steers (290 kg) in a 94-d comparative slaughter trial. There were no interactions between supplemental fat and monensin (P greater than .20). Monensin supplementation did not affect rate or composition of gain (P greater than .20), but supplementation reduced (P less than .05) feed intake and feed required per unit weight gain 3.6%. Fat supplementation increased (P less than .01) fat and energy gain 12.5 and 10.3%, respectively, and the NEm and NEg content of the diet 7.5 and 8.4%, respectively. Trial 3 utilized four crossbred beef steers (220 kg) with cannulas in the rumen, proximal duodenum and distal ileum. There were no interactions between supplemental fat and monensin with respect to site of digestion (P greater than .20). Supplemental fat did not affect (P greater than .20) organic matter, starch, fiber or N digestion. Intestinal digestibility of fat averaged 77.3%. Monensin increased (P less than .10) intestinal digestibility of fat 7.4%. There were negative associative effects between supplemental fat and monensin on ruminal acetate:propionate ratios and estimated methane production. It was concluded that the feeding value of feed fat is underestimated in tables of feed standards currently in use, and that the net effects of monensin on these estimates are additive.