Maduramicin and tiamulin compatibility in broiler chickens

Badiola, J.J.; Luco, Daniel Fernández de; Pérez, Valentín Pérez; Vargas, Matthew; Luján, Lluís; Marin, Julio Francisco Valiati

doi:10.1080/03079459408418971

Cited by 9 publications

(6 citation statements)

References 8 publications

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“…Animal protein, furazolidone, tiamulin, macrolide antibiotics, and neomycin-permethrin can potentiate ionophore toxicity in various species of animals. 2,3,5,35 Samples of suspect DDG contained residues of the antibiotics erythromycin and clarithromycin and related analogs. Erythromycin and clarithromycin belong to the macrolide class of antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Toxicosis in Cattle from Concurrent Feeding of Monensin and Dried Distiller's Grains Contaminated with Macrolide Antibiotics

et al. 1999

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Consumption of monensin-containing feed contaminated with macrolide antibiotic residues resulted in the death of cattle from multiple feedlots in south-central Kansas. Cattle were fed milo dried distiller's grains (DDG) with solubles from a common source in conjunction with the ionophore antibiotic, monensin. Deaths occurred as early as 72-96 hours after feeding and were preceded by either no premonitory signs or 1 or more of the following: anorexia, depression, dyspnea, locomotor deficits, and recumbency. Significant gross lesions were pulmonary and mesenteric edema, hepatomegaly, and generalized myocardial and skeletal muscle pallor that was confirmed histologically as acute myodegeneration and necrosis. Other significant histologic lesions included centrolobular hepatocellular necrosis, congestion, and pulmonary interstitial and alveolar edema with fibrin exudation. Animals that survived beyond 6 weeks had poor weight gain and coalescing foci of myocardial fibrosis with residual myocardial degeneration. Analysis of trace mineral supplements for monensin were within the manufacturer's label range. The DDG samples from affected feedlots had 50-1,500 ppm of erythromycin, clarithromycin, and related macrolide antibiotic analogues, which originated in the alcohol residue. In a preliminary feeding trial, cattle fed this contaminated DDG in combination with monensin had clinical signs and died with gross and histologic findings comparable to those of the field cases. Even though rations supplemented with the contaminated DDG contained approved levels of monensin, the clinical and postmortem findings were consistent with those expected for monensin toxicosis. The presence of macrolide antibiotic residues in the contaminated feed appeared to affect the biotransformation of otherwise nontoxic levels of monensin, leading to clinical ionophore toxicosis.

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Section: Discussionmentioning

confidence: 99%

Toxicosis in Cattle from Concurrent Feeding of Monensin and Dried Distiller's Grains Contaminated with Macrolide Antibiotics

et al. 1999

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“…Clinically important interactions between ionophore anticoccidials and the antibiotic tiamulin (and other antibiotics) are well-known phenomena in chickens, turkeys and other species (EFSA, 2004). The severity of adverse effects varies depending on the ionophore itself, reaching from increased mortality to only transient performance depression (Badiola, et al, 1994;Schuhmacher, et al, 2006). Badiola (1994) studied the compatibility of maduramicin ammonium (5 mg/kg feed) with tiamulin (270 mg/L drinking water from day 28 to 31) for 52 days.…”

Section: Incompatibilities and Interactionsmentioning

confidence: 99%

“…The severity of adverse effects varies depending on the ionophore itself, reaching from increased mortality to only transient performance depression (Badiola, et al, 1994;Schuhmacher, et al, 2006). Badiola (1994) studied the compatibility of maduramicin ammonium (5 mg/kg feed) with tiamulin (270 mg/L drinking water from day 28 to 31) for 52 days. As the only adverse effect of the simultaneous administration, the authors found a transient depression of feed intake and growth during and following the 14-day period of tiamulin administration.…”

Section: Incompatibilities and Interactionsmentioning

confidence: 99%

Scientific Opinion on safety and efficacy of Cygro® 10G (maduramicin ammonium α) for chickens for fattening

2011

EFSA Journal

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Cygro® 10G is a coccidiostat for chickens for fattening containing 10 g of maduramicin ammonium /kg additive. The highest proposed dose (6 mg/kg) appeared near to the intolerance level. Maduramicin ammonium can inhibit the growth of some Gram-positive micro-organisms, but measurable adverse effects on the overall gut flora are unlikely. Maduramicin was excreted rapidly in chickens, mainly unchanged. O-demethylation represented the main metabolic pathway in chickens and rats. Tissue residue kinetics indicate a rapid decline in all tissues. Liver was the target tissue; maduramicin the marker residue in all tissues. Maduramicin ammonium was not mutagenic. It was concluded from chronic toxicity/carcinogenicity studies in rats and mice that maduramicin ammonium  is not a carcinogen. The lowest NOAEL of 0.1 mg/kg bw/day was found in a chronic rat study and in a multi-generation study in rats. An ADI of 1 g maduramicin/kg bw was derived, applying an uncertainty factor of 100, which corresponds to an acceptable daily exposure of 60 g per person. After a threeday withdrawal, human exposure to maduramicin residues complied with the ADI (42 %). MRLs of 0.15 mg maduramicin/kg liver and skin/fat, 0.1 mg/kg kidney and 0.03 mg/kg muscle were proposed. Maduramicin ammonium showed a high systemic toxicity after dermal application. Although Cygro ® 10G did not show skin and eye irritating or skin sensitising properties, any direct dermal contact with the additive must be avoided. Cygro ® 10G has a low dusting potential and from the result of acute inhalation toxicity study it was described as harmful if inhaled. Consequently, inhalation should be minimised. Cygro ® 10G at the maximum dose of 6 mg maduramicin/kg feed does not pose a risk for the environment. The dose-range, 5-6 mg maduramicin/kg complete feed is effective in controlling coccidiosis in chickens for fattening. SUMMARYFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDP) was asked to deliver a scientific opinion on the safety and efficacy of Cygro ® 10G for chickens for fattening. The additive Cygro ® 10G is a preparation of the polyether ionophore maduramicin ammonium produced by fermentation. It is intended to be used to control coccidiosis in chickens for fattening. The proposed inclusion level of Cygro ® 10G is 5 to 6 mg maduramicin ammonium /kg complete feed for chickens for fattening.The highest proposed dose (6 mg/kg) appeared near to the intolerance level of chickens for fattening and no margin of safety could be derived from the data. Although maduramicin ammonium , in common with other ionophores, can inhibit the growth of Gram-positive micro-organisms, it is unlikely that this would result in any measurable adverse effect on the overall gut flora.Maduramicin was excreted rapidly in chickens. Steady state was observed after three days in the excreta, but after six days in plasma. Maduramicin was the main compound excreted (26 %). Odemethylation represented the main metaboli...

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“…Clinically important interactions between ionophore anticoccidials and the antibiotic tiamulin (and other antibiotics) are well-known phenomena in chickens, turkeys and other species (EFSA, 2004). In assessing the results of a study of Badiola et al (1994), the FEEDAP Panel was not in a position to establish the full compatibility of Maα and tiamulin in chickens for fattening (EFSA FEEDAP Panel, 2011b). The same interaction is consequently assumed for Maα in turkeys for fattening.…”

Section: Incompatibilities and Interactionsmentioning

confidence: 99%

“…In assessing the results of a study of Badiola et al (1994), the FEEDAP Panel was not in a position to establish the full compatibility of Maα and tiamulin in chickens for fattening (EFSA FEEDAP Panel, 2011b). The same interaction is consequently assumed for Maα in turkeys for fattening.…”

Section: Incompatibilities and Interactionsmentioning

confidence: 99%

Scientific Opinion on the safety and efficacy of Cygro® 10G (maduramicin ammonium‐α) for turkeys

2015

EFS2

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Cygro® 10G is a coccidiostat for turkeys for fattening containing 10 g of the polyether ionophore maduramicin ammonium-α (Maα)/kg additive. The maximum proposed dose (5 mg Maα/kg) is considered safe for turkeys with a margin of safety of 2.5. It is unlikely that there will be any measurable adverse effects of Maα on the overall gut flora. Maα is absorbed and excreted rapidly. O-demethylation is the main metabolic pathway in turkeys and rats. Maduramicin-α is the marker residue in the liver and skin/fat. Maα is not mutagenic or carcinogenic. The lowest no observed adverse effect level (NOAEL) of 0.1 mg/kg bw per day is found in chronic and multi-generation studies in rats. An acceptable daily intake (ADI) of 1 g Maα/kg bw (60 μg per person) is derived, applying an uncertainty factor of 100. After a three-day withdrawal, human exposure to maduramicin residues complies with the ADI (17 %). Maximum residue limits (MRL) of 0.15 mg maduramicin/kg liver and skin/fat, 0.1 mg/kg kidney and 0.03 mg/kg muscle are proposed. Although Cygro ® 10G is not an irritant to skin or eyes or a dermal sensitiser, any direct dermal contact should be avoided owing to the high systemic toxicity of Maα after dermal application. Inhalation of Cygro ® 10G is considered a hazard; therefore a risk to persons handling the additive cannot be excluded. The use of Cygro ® 10G is safe for the environment, with the exception of soils with pH values above 7.2, for which no data were available. This conclusion does not extend to effects on organisms living on manure which are not assessed under the current regulation. Based on the recent studies (floor pen studies, field studies and sensitivity studies), the efficacy of Cygro ® 10G in turkeys for fattening has not been sufficiently demonstrated.

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Maduramicin and tiamulin compatibility in broiler chickens

Cited by 9 publications

References 8 publications

Toxicosis in Cattle from Concurrent Feeding of Monensin and Dried Distiller's Grains Contaminated with Macrolide Antibiotics

Toxicosis in Cattle from Concurrent Feeding of Monensin and Dried Distiller's Grains Contaminated with Macrolide Antibiotics

Scientific Opinion on safety and efficacy of Cygro® 10G (maduramicin ammonium α) for chickens for fattening

Scientific Opinion on the safety and efficacy of Cygro® 10G (maduramicin ammonium‐α) for turkeys

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