monensin and narasin

The emergence of antimicrobial resistance represents a serious human and animal health risk. Good antimicrobial stewardship is essential to prolong the lifespan of existing antibiotics, and new strategies are required to combat infections in man and animals.. To determine the in vitro interaction of ionophores (narasin or monensin) with antimicrobial adjuvants (N-acetylcysteine (NAC), Tris-EDTA or disodium EDTA) against bacterial strains representing pathogens associated with canine otitis externa (OE).. American Type Culture Collection (ATCC) strains Staphylococcus aureus 29213, Pseudomonas aeruginosa 27853 and P. aeruginosa biofilm producer PAO1, and a clinical isolate of Proteus mirabilis from a case of canine OE were tested.. A 2D microdilution checkerboard method was used, allowing calculation of fractional inhibitory concentration index (FICI), dose reduction index (DRI) and plotting of isobolograms.. The combination of narasin with either Tris-EDTA or disodium EDTA produced additive effects (FICI = 0.75) against P. aeruginosa ATCC 27853 and P. aeruginosa biofilm producer ATCC PAO1. An additive effect (FICI = 0.53-0.75) was found against S. aureus ATCC 29213 when narasin or monensin were combined with NAC. The highest DRI (32-fold) was found with monensin/NAC where the MIC of monensin was reduced from 4 to 0.125 μg/mL.. The combination of narasin with Tris-EDTA or disodium EDTA is a promising strategy to inhibit the intrinsic resistance elements of Gram-negative bacteria. These novel combinations potentially could be useful as a multimodal approach to treat mixed infections in canine OE.. L’émergence de résistances aux antimicrobiens représente un risque pour la santé humaine et animale. Une bonne utilisation des antimicrobiens est essentielle pour prolonger la durée de vie des antibiotiques actuels et de nouvelles stratégies sont nécessaires pour combattre les infections chez l'homme et l'animal. HYPOTHÈSES/OBJECTIFS: Déterminer les interactions in vitro des ionophores (narasine ou monensine) et des adjuvants antimicrobiens (NAC N-acetylcystéine, Tris-EDTA ou disodium EDTA) contre les souches bactériennes pathogènes associées aux otites canines externes (OE).. Les souches de l’ATCC (American Type Culture Collection) Staphylococcus aureus 29213, Pseudomonas aeruginosa 27853 et P. aeruginosa productrice de biofilm PAO1, et une souche clinique de Proteus mirabilis issue d'un cas d’OE canine ont été testées. MATÉRIELS ET MÉTHODES: Une méthode de microdilution 2D en damier a été utilisée, permettant un calcul de FICI (fractional inhibitory concentration index), de l'index de réduction de dose (DRI) et des marqueurs d'isobologrammes. RÉSULTATS: L'association de narasine, soit avec Tris-EDTA soit avec disodium EDTA, a produit des effets additifs (FICI = 0.75) contre P. aeruginosa ATCC 27853 et P. aeruginosa producteur de biofilm ATCC PAO1. Un effet additif (FICI = 0.53-0.75) a été trouvé contre S. aureus ATCC 29213 lorsque la narasine ou la monensine étaient combinés avec NAC. Le plus haut DRI (32 fois) a été trouvé avec monensine/NAC là ou le MIC était diminué de 4 à 0.125 μg/mL.. L'association de la narasine avec le Tris-EDTA ou le disodium EDTA est une stratégie prometteuse pour inhiber les éléments de résistance des bactéries Gram-négatives. Ces nouvelles associations peuvent potentiellement être utiles dans une approche multimodale pour le traitement des infections mixtes des OE canines.. INTRODUCCIÓN: la aparición de resistencia a los antimicrobianos representa un grave riesgo para la salud humana y animal. Una razonable administración de antimicrobianos es esencial para prolongar la vida útil de los antibióticos existentes, y se requieren nuevas estrategias para combatir las infecciones en seres hunanos y animales. HIPÓTESIS/OBJETIVOS: determinar la interacción in vitro de los ionóforos (narasina o monensina) con adyuvantes antimicrobianos (N-acetilcisteína (NAC), Tris-EDTA o EDTA disódico) contra cepas bacterianas que representan patógenos asociados con la otitis externa canina (OE). ANIMALES/AISLADOS: cepas de la American Type Culture Collection (ATCC) Staphylococcus aureus 29213, Pseudomonas aeruginosa 27853 y P. aeruginosa productor de biopelículas PAO1, y un aislado clínico de Proteus mirabilis de un caso de OE canina. MÉTODOS Y MATERIALES: se usó un método de tablero de cuadrículas de microdilución 2D, que permite calcular el índice de concentración inhibitoria fraccional (FICI), el índice de reducción de dosis (DRI) y el trazado de isobologramas. RESULTADOS: la combinación de narasina con Tris-EDTA o EDTA disódico produjo efectos aditivos (FICI = 0,75) frente a P. aeruginosa ATCC 27853 y P. aeruginosa productor de biopelículas ATCC PAO1. Se encontró un efecto aditivo (FICI = 0,53-0,75) frente a S. aureus ATCC 29213 cuando se combinaron narasina o monensina con NAC. El DRI más alto (32 veces) se encontró con monensina/NAC donde la MIC se redujo de 4 a 0,125 μg/ml. CONCLUSIONES E IMPORTANCIA CLÍNICA: la combinación de narasina con Tris-EDTA o EDTA disódico es una estrategia prometedora para inhibir los elementos de resistencia intrínseca de las bacterias Gram-negativas. Estas nuevas combinaciones podrían ser útiles como un enfoque multimodal para tratar infecciones mixtas en la OE canina.. Das Auftreten von antimikrobieller Resistenz bedeutet ein schwerwiegendes Gesundheitsrisiko für Mensch und Tier. Eine gute antimikrobielle Stewardship ist essentiell, um die Lebensdauer existierender Antibiotika zu verlängern, außerdem sind neue Strategien nötig, um Infektionen bei Mensch und Tier zu bekämpfen.. Die Bestimmung der in vitro Interaktion von Ionophoren (Narasin oder Monensin) mit antimikrobiellen Adjuvantien (N-Acetylcystein (NAC), Tris-EDTA oder Disodium EDTA) gegenüber Bakterienstämmen, die Pathogene darstellen, die bei einer Otitis externa (OE) des Hundes gerne auftreten.. Es wurden Stämme aus der American Type Culture Collection (ATCC) von Staphylococcus aureus 29213, Pseudomonas aeruginosa 27853 and P. aeruginosa Biofilm Produzent PAO1, sowie ein klinisches Isolat von Proteus mirabilis von einem Hund mit OE getestet.. Es wurde eine 2D Mikrodilutionsschachbrettmethode verwendet, welche die Kalkulation des fraktionellen Hemmstoffkonzentrationsindex (FICI), des Dosisreduktionsindex (DRI) und ein Plotting des Isobologramms erlaubte.. Die Kombination von Narasin mit entweder Tris-EDTA oder Disodium EDTA zeigte additive Wirkung (FICI = 0,75) gegen P. aeruginosa ATCC 27853 und P. aeruginosa Biofilm Produzent ATCC PAO1. Eine additive Wirkung (FICI = 0,53-0,75) wurde gegen S. aureus ATCC 29213 gefunden, wenn Narasin oder Monensin mit NAC kombiniert worden waren. Die höchste DRI (32-fach) wurde mit Monensin/NAC gefunden, wodurch die MIC von 4 auf 0,125 µg/mL reduziert wurde.. Die Kombination von Narasin mit Tris-EDTA oder Disodium EDTA ist eine vielversprechende Strategie, um die Elemente der intrinsischen Resistenz von Gram-negativen Bakterien zu inhibieren. Diese neuen Kombinationen könnten möglicherweise als multimodale Herangehensweise nützlich sein, um Mischinfektionen bei der OE des Hundes zu behandeln.. 背景: 抗菌薬耐性の出現は、人間と動物の深刻な健康リスクを表している。既存の抗生物質のライフスパンを延ばすためには、優れた抗菌薬管理が不可欠であり、人間や動物の感染症と闘うには新しい戦略が必要である。 仮説/目的: 本研究の目的は、犬外耳炎(OE)に関連する病原体を表す細菌株に対するイオノフォア(ナラシンまたはモネンシン)および抗菌アジュバント(N-アセチルシステイン(NAC)、Tris-EDTAまたはEDTA二ナトリウム)のin vitroにおける相互作用を決定することである。 被験動物/分離株: 黄色ブドウ球菌American Type Culture Collection(ATCC)29213、緑膿菌ATCC 27853および緑膿菌バイオフィルム産生株ATCC PAO1、および犬外耳炎症例からProteus mirabilisの臨床分離株を検査した。 材料と方法: 2D微量希釈チェッカーボード法を使用して、分別阻害濃度指数(FICI)、線量低減指数(DRI)の計算およびアイソボログラム法のプロッティングを可能にした。 結果: ナラシンとTris-EDTAまたはEDTA二ナトリウムの併用は、緑膿菌ATCC 27853および緑膿菌バイオフィルム産生株ATCC PAO1に対して相加効果(FICI = 0.75)をもたらした。ナラシンまたはモネンシンをNACと併用した場合、黄色ブドウ球菌ATCC 29213に対して相加効果(FICI = 0.53-0.75)を認めた。最も高いDRI(32倍)は、MICが4から0.125μg/ mLに減少したモネンシン/ NACで検出された。 結論と臨床的重要性: ナラシンとTris-EDTAまたは二ナトリウムEDTAの併用は、グラム陰性菌固有の耐性要素を抑制する有望な戦略である。これらの新しい併用法は、犬外耳炎の混合感染症治療のマルチモーダルアプローチとして有用である可能性がある。.. 背景: 抗菌素耐药问题会带来人类和动物严重的健康风险。良好的抗菌素管理对于延长现有抗生素的产品寿命至关重要,需要采取新的策略来对抗人和动物的感染。 假设/目的: 确定离子型抗生素(那拉菌素或莫能菌素)与抗微生物佐剂(N-乙酰半胱氨酸(NAC),Tris-EDTA或EDTA二钠)相互作用后,抗犬外耳炎(OE)病原体的体外效果。 动物/分离株: 测试美国菌种保藏中心(ATCC)的金黄色葡萄球菌29213,铜绿假单胞菌27853和铜绿假单胞菌生物膜形成物PAO1,以及从犬OE病例中分离出的变形杆菌。 方法和材料: 采用2D微稀释棋盘法,计算分级抑制浓度指数(FICI)、剂量降低指数(DRI)并绘制等效线图。 结果: 那拉菌素与Tris-EDTA或EDTA二钠的组合,对铜绿假单胞菌ATCC 27853和铜绿假单胞菌生物膜形成物ATCC PAO1具有协同作用(FICI = 0.75)。 当那拉菌素或莫能菌素与NAC联用时,发现对金黄色葡萄球菌ATCC 29213同样具有协同作用(FICI = 0.53-0.75)。 莫能菌素/ NAC的DRI最高(32倍),MIC从4降至0.125μg/ mL。 结论和临床意义: 对抑制革兰氏阴性细菌的固有耐药因素,那拉菌素联合Tris-EDTA或EDTA二钠是一种有前途的策略。 这些新颖的联合,可作为犬OE混合感染的多模式治疗方案。.. O surgimento de resistência antimicrobiana representa um sério risco à saúde humana e animal. Boas práticas de administração de antimicrobianos são essenciais para prolongar a vida útil dos antibióticos existentes, e novas estratégias são necessárias para combater infecções no homem e nos animais. HIPÓTESE/OBJETIVOS: Determinar a interação in vitro de ionóforos (narasina ou monensina) com adjuvantes antimicrobianos (N-acetilcisteína (NAC), Tris-EDTA ou EDTA dissódico) contra cepas bacterianas associados à otite externa canina (OE).. As cepas padrão registradas na American Type Culture Collection (ATCC) de Staphylococcus aureus 29213, Pseudomonas aeruginosa 27853, P. aeruginosa PAO1 produtora de biofilme, e um isolado clínico de Proteus mirabilis oriundo de um caso de OE canino foram testados. MÉTODOS E MATERIAIS: Utilizou-se o método de checkerboard em microdiluição 2D, permitindo o cálculo do índice de concentração inibitória fracionária (FICI), índice de redução da dose (DRI) e plotagem de isobologramas.. A combinação de narasina com Tris-EDTA ou EDTA dissódico prossuiu efeitos aditivos (FICI = 0,75) contra P. aeruginosa ATCC 27853 e P. aeruginosa ATCC PAO1 produtora de biofilme. Um efeito aditivo (FICI = 0,53-0,75) foi encontrado contra S. aureus ATCC 29213 quando narasina ou monensina foram combinadas com NAC. O maior DRI (32 vezes) foi encontrado com monensina / NAC, onde a CIM foi reduzida de 4 para 0,125 μg / mL. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: A combinação de narasina com Tris-EDTA ou EDTA dissódico é uma estratégia promissora para inibir os elementos intrínsecos de resistência de bactérias Gram-negativas. Essas novas combinações poderiam ser potencialmente úteis como uma abordagem multimodal no tratamento de infecções mistas nas OEs caninas.

Topics: Adjuvants, Pharmaceutic; Animals; Anti-Bacterial Agents; Bacteria; Biofilms; Dog Diseases; Dogs; Drug Synergism; Ionophores; Microbial Sensitivity Tests; Monensin; Otitis Externa; Proteus mirabilis; Pseudomonas aeruginosa; Pyrans; Staphylococcus aureus

Topics: Animals; Chickens; Chromatography, Liquid; Coccidiosis; Eggs; Food Analysis; Humans; Lactones; Lasalocid; Liquid-Liquid Extraction; Monensin; Nigericin; Piperidines; Poultry; Pyrans; Quinazolinones; Robenidine; Tandem Mass Spectrometry; United States; United States Food and Drug Administration

Topics: Acetylcysteine; Animals; Anti-Infective Agents; Bacteria; Biofilms; Dog Diseases; Dogs; Edetic Acid; Enrofloxacin; Ionophores; Microbial Sensitivity Tests; Monensin; Otitis Externa; Pyrans

Ionophore antimicrobials are heavily used in the livestock industries, both for preventing animal infection by coccidia protozoa and for increasing feed efficiency. Ionophores are excreted mostly unmetabolized and are released into the environment when manure is land-applied to fertilize croplands. Here, an analytical method was optimized to study the occurrences of five ionophore residues (monensin, lasalocid, maduramycin, salinomycin, and narasin) in dairy manure after solid-liquid separation and further treatment of the liquid manure by a membrane-based treatment system. Ionophore residues from the separated solid manure (dewatered manure) and suspended solids of manure slurry samples were extracted using ultrasonication with methanol, followed by sample clean-up using solid phase extraction (SPE) and subsequent analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The use of an ethyl acetate and methanol (1:1 v:v) mixture as an SPE eluent resulted in higher recoveries and lower method quantitation limits (MQL), when compared to using methanol. Overall recoveries from separated solid manure ranged from 73 to 134%. Liquid manure fractions were diluted with Nanopure™ water and cleaned up using SPE, where recoveries ranged from 51 to 100%. The developed extraction and LC-MS/MS methods were applied to analyze dairy manure samples subjected to an advanced manure treatment process involving a membrane-based filtration step (reverse osmosis). Monensin and lasalocid were detected at higher concentrations in the suspended solid fractions (4.40-420 ng/g for lasalocid and 85-1950 ng/g for monensin) compared to the liquid fractions (

Topics: Animals; Anti-Infective Agents; Cattle; Chromatography, Liquid; Coccidia; Coccidiosis; Ionophores; Lactones; Lasalocid; Manure; Methanol; Monensin; Pyrans; Solid Phase Extraction; Tandem Mass Spectrometry

Topics: Animals; Anti-Bacterial Agents; Biofilms; Cattle; Female; Gram-Positive Bacteria; Ionophores; Lasalocid; Mastitis, Bovine; Microbial Sensitivity Tests; Monensin; Pyrans; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Streptococcus

The cytotoxic effect of monensin, narasin and salinomycin followed by their co-action with silybin in the cell line cultures of human hepatoma (HepG2), chicken hepatoma (LMH) or rat myoblasts (L6) have been investigated. The effective concentration of the studied ionophoric polyethers has been assessed within two biochemical endpoints: mitochondrial activity (MTT assay) and membrane integrity (LDH assay) after 24h incubation of each compound and farther, the cytotoxicity influenced in course of their interaction with silybin was determined. The most affected endpoints were found for inhibition of mitochondrial activity of the hepatoma cell lines and their viability depended on concentration of the ionophoric polyether, as well as on the cell line tested. The rat myoblasts were more sensitive target for cellular membrane damage when compared to inhibition of mitochondrial activity. An interaction between the ionophoric polyethers and silybin resulted a considerable cytotoxicity decrease within all studied cell lines; the combination index (CI) showed differences of interaction mode and dependence on cell culture, concentration of silybin, as well as the assay used. The obtained results are of interest in respect to recent findings on applicability of salinomycin and monensin for human therapy.

Topics: Animals; Cell Line; Cell Line, Tumor; Cell Survival; Chickens; Drug Interactions; Hep G2 Cells; Humans; Monensin; Myoblasts; Pyrans; Rats; Silybin; Silymarin

Ionophore antibiotics (IPAs) are polyether compounds used in broiler feed to promote growth and control coccidiosis. Most of the ingested IPAs are excreted into broiler litter (BL), a mixture of excreta and bedding material. BL is considered a major source of IPAs released into the environment as BL is commonly used to fertilize agricultural fields. This study investigated IPA biodegradation in BL and soil microcosms, as a process affecting the fate of IPAs in the environment. The study focused on the most widely used IPAs, monensin (MON), salinomycin (SAL), and narasin (NAR). MON was stable in BL microcosms at 24-72% water content (water/wet litter, w/w) and 35-60 °C, whereas SAL and NAR degraded under certain conditions. Factor analysis was conducted to delineate the interaction of water and temperature on SAL and NAR degradation in the BL. A major transformation product of SAL and NAR was identified. Abiotic reaction(s) were primarily responsible for the degradation of MON and SAL in nonfertilized soil microcosms, whereas biodegradation contributed significantly in BL-fertilized soil microcosms. SAL biotransformation in soil microcosms yielded the same product as in the BL microcosms. A new primary biotransformation product of MON was identified in soil microcosms. A field study showed that MON and SAL were stable during BL stacking, whereas MON degraded after BL was applied to grassland. The biotransformation product of MON was also detected in the top soil layer where BL was applied.

Topics: Animals; Anti-Bacterial Agents; Biodegradation, Environmental; Chickens; Fertilizers; Ionophores; Manure; Monensin; Pyrans; Soil Microbiology; Soil Pollutants; Temperature; Veterinary Drugs; Water

The veterinary ionophore antibiotics (IPAs) are extensively used as coccidiostats and growth promoters and are released to the environment via land application of animal waste. Due to their propensity to be transported with runoff, IPAs likely end up in surface waters where they are subject to photodegradation. This study is among the first to investigate the photodegradation of three commonly used IPAs, monensin (MON), salinomycin (SAL) and narasin (NAR), under UV and solar irradiation. Results showed that MON was persistent in a deionized (DI) water matrix when exposed to UV and sunlight, whereas SAL and NAR could undergo direct photolysis with a high quantum yield. Water components including nitrate and dissolved organic matter had a great impact on the photodegradation of IPAs. A pseudosteady state kinetic model was successfully applied to predict IPAs' photodegradation rates in real water matrices. Applying LC/MS/MS, multiple photolytic transformation products of IPAs were observed and their structures were proposed. The direct photolysis of SAL and NAR occurred via cleavage on the ketone moiety and self-sensitized photolysis. With the presence of nitrate, MON was primarily degraded by hydroxyl radicals, whereas SAL showed reactivity toward both hydroxyl and nitrogen-dioxide radicals. Additionally, toxicity tests showed that photodegradation of SAL eliminated its antibiotic properties against Bacillus subtilis.

Topics: Anti-Bacterial Agents; Ionophores; Kinetics; Monensin; Nitrates; Photolysis; Pyrans; Quantum Theory; Spectrum Analysis; Tandem Mass Spectrometry; Toxicity Tests; Ultraviolet Rays; Veterinary Drugs; Water; Water Pollutants, Chemical

Hydrolytic and photolytic degradation were investigated for the ionophore antibiotics lasalocid, monensin, salinomycin, and narasin. The hydrolysis study was carried out by dissolving the ionophores in solutions of pH 4, 7, and 9, followed by incubation at three temperatures of 6, 22, and 28 °C for maximum 34 days. Using LC-MS/MS for chemical analysis, lasalocid was not found to hydrolyse in any of the tested environments. Monensin, salinomycin, and narasin were all stable in neutral or alkaline solution but hydrolysed in the solution with a pH of 4. Half-lives at 25 °C were calculated to be 13, 0.6, and 0.7 days for monensin, salinomycin, and narasin, respectively. Absorbance spectra from each compound indicated that only lasalocid is degraded by photolysis (half-life below 1 h) due to an absorbance maximum around 303 nm, and monensin, salinomycin, and narasin are resistant to direct photolysis because they absorb light of environmentally irrelevant wavelengths.

Topics: Anti-Bacterial Agents; Half-Life; Hydrogen-Ion Concentration; Ionophores; Lasalocid; Models, Chemical; Monensin; Photolysis; Pyrans; Temperature; Water Pollutants, Chemical

Ionophore antibiotics (IPAs) are polyether antimicrobials widely used in the livestock industry and may enter the environment via land application of animal waste and agricultural runoff. Information is scarce regarding potential transformation of IPAs under environmental conditions. This study is among the first to identify the propensity of IPAs to undergo acid-catalyzed transformation in mildly acidic aquatic systems and characterize the reactions in depth. The study focused on the most widely used monensin (MON) and salinomycin (SAL), and also included narasin (NAR) in the investigation. All three IPAs are susceptible to acid-catalyzed transformation. MON reacts much more slowly than SAL and NAR and exhibits a different kinetic behavior that is further evaluated by a reversible reaction kinetic model. Extensive product characterization identifies that the spiro-ketal group of IPAs is the reactive site for the acid-catalyzed hydrolytic transformation, yielding predominantly isomeric and other products. Toxicity evaluation of the transformation products shows that the products retain some antimicrobial properties. The occurrence of IPAs and isomeric transformation products is also observed in poultry litter and agricultural runoff samples. Considering the common presence of mildly acidic environments (pH 4-7) in soils and waters, the acid-catalyzed transformation identified in this study likely plays an important role in the environmental fate of IPAs.

Topics: Acetic Acid; Anti-Bacterial Agents; Bacillus subtilis; Hydrochloric Acid; Hydrogen-Ion Concentration; Ionophores; Kinetics; Models, Chemical; Monensin; Pyrans; Soil Pollutants

A published confirmatory method for the quantitative determination of four ionophoric coccidiostats (lasalocid, monensin, salinomycin and narasin) in eggs and broiler meat has been further developed. It is proposed for replacement of liquid chromatography methods previously used in analysis of ionophoric coccidiostats. The samples were extracted with acetonitrile and purified on a silica solid phase extraction column. Purified samples were analysed by liquid chromatography-mass spectrometry and the method, was validated according to the Commission Decision 2002/657/EC. The validation parameters selectivity, linearity, specificity, precision, recovery, decision limit (CCalpha) and detection capability (CCbeta) were determined. The recoveries of coccidiostats analysed ranged from 64-99% in eggs and 62-100% in broiler meat. CCalpha varied from 0.8-1.4 microg/kg in eggs and from 1.5-2.5 microg/kg in broiler meat. CCbeta varied from 0.9 microg/kg to 2.0 microg/kg in eggs and from 1.7-3.2 microg/kg in broiler meat.

Topics: Animals; Chickens; Chromatography, Liquid; Coccidiostats; Eggs; Food Contamination; Lasalocid; Mass Spectrometry; Meat; Monensin; Pyrans; Reproducibility of Results

A sensitive and selective liquid chromatographic tandem mass spectrometric method (LC/MS/MS) for the simultaneous detection of the ionophoric coccidiostats narasin, monensin, lasalocid and salinomycin in whole eggs has been developed. A very simple sample preparation consisting of an extraction with an organic solvent was carried out. Sample extracts were injected into the LC/MS/MS system on a C18 column and an isocratic elution was performed. Nigericin was used as internal standard. The precursor ions produced by electrospray positive ionisation were selected for collisional dissociation with argon into product ions. Validation of the methods was performed based on Commission Decision 2002/657/EC.1 CC(alpha) was found to be 1 microg/kg for all four compounds. Monitoring of Belgian egg samples in 2004 revealed that residues of salinomycin, lasalocid and monensin could be found.

Topics: Animals; Chromatography, High Pressure Liquid; Coccidiostats; Eggs; Food Contamination; Ionophores; Lasalocid; Monensin; Pyrans; Spectrometry, Mass, Electrospray Ionization

A rapid and very effective analytical procedure for the simultaneous determination of four polyether antibiotics (PEs) lasalocid, monensin, salinomycin and narasin in poultry feeds was tested. PEs were extracted from samples using methanol and without and clean-up derivatized with 2,4-dinitrophenylhydrazine (DNP) in an acidic medium at 55 degrees C. The derivatization mixture was analyzed directly on an ODS column (150 x 4.6 mm, 5 microns) with methanol--1.5% aqueous acetic acid (90:10, v/v) as eluent and UV detection was carried out at 305/392 nm. The recoveries of the PEs from spiked samples were 85-100% with RSDs of 4-10% in a concentration range of 50-150 mg/kg.

Topics: Animal Feed; Animals; Chromatography, Liquid; Coccidiostats; Indicators and Reagents; Lasalocid; Monensin; Phenylhydrazines; Poultry; Pyrans; Reference Standards; Reproducibility of Results; Spectrophotometry, Ultraviolet; Veterinary Drugs

Coccidia were isolated from a commercial broiler farm with a history of suspected drug resistance. The sensitivity profiles of the Eimeria spp. isolates against the anticoccidial drugs nicarbazin (NIC), narasin (NAR), halofuginone (HAL), salinomycin (SAL), meticlorpindol plus methylbenzoquate (MET), and monensin (MON) at the recommended dose levels were followed in three battery trials (B1, B2, B3) corresponding to a field study over three periods of commercial broiler keeping (F1, F2, F3). Shuttle programs were performed in F1 (NIC/MON) and in F2 (MET/MON) while only SAL was used in F3. Eimeria acervulina and E. tenella were isolated from indicator birds in F1 while only E. acervulina could be found during F2 and F3. In trial B1 the isolate from F1 was identified as resistant against HAL and partly resistant against NIC and MON, the two drugs that were used in F1. Following the replacement of NIC in the starter feed by MET the respective isolate from F2 showed no resistance against ionophores (trial B2) while partial resistance against HAL was still present. Since SAL was the most efficient drug in B1 and B2 only this drug was applied in F3. Apart from a resistance against HAL no resistance against any of the other tested anticoccidials was found in the isolate from F3. SAL controlled coccidiosis efficiently in the field and best productivity was recorded in F3. This study shows that battery trials have a good predictive value in respect to the efficacy of anticoccidials under the conditions of commercial broiler production.

Topics: Animal Husbandry; Animals; Chickens; Clopidol; Coccidiosis; Coccidiostats; Drug Resistance; Eimeria; Feces; Food Industry; Ionophores; Monensin; Nicarbazin; Piperidines; Poultry Diseases; Predictive Value of Tests; Pyrans; Quinazolines; Quinazolinones; Quinolones

Monensin, salinomycin and narasin were detectable in six, two and one, respectively, out of 161 eggs surveyed in Northern Ireland in 1994. In all cases, the concentrations detected were less than 2.5 ng/g. Lasalocid was detectable in 107 eggs at concentrations ranging from 0.3 to 129 ng/g. Cross-contamination of unmedicated feeds with monensin during feed manufacture (up to eight batches of unmedicated feed contaminated with monensin) was similar to that previously observed for lasalocid (up to nine batches contaminated). Therefore differences in the incidence in eggs could not be explained by differential carry-over during feed manufacture. In a feeding trial it was shown that the relative ability of monensin, salinomycin and lasalocid to accumulate in eggs was in the ratio 0.12:3.3:63 ng/g egg per mg/kg feed, respectively. This indicated that the potential for monensin and salinomycin to cause residues in eggs was very low, by comparison with lasalocid. In 1995, a granular formulation of the lasalocid premix was introduced into the United Kingdom that decreased the carry-over of this drug from medicated to unmedicated feed. Six months after the introduction of this formulation, the incidence of lasalocid residues in eggs (21%) was lower than that found (66.5%) in an earlier survey (1994) carried out, and published, by this laboratory.

Topics: Animal Feed; Animals; Chickens; Coccidiostats; Drug Residues; Eggs; Food Contamination; Humans; Incidence; Ionophores; Lasalocid; Monensin; Northern Ireland; Pyrans

The effects of the growth promoters avoparcin and avilamycin and the ionophore anticoccidials maduramicin, narasin and monensin on the growth of Clostridium perfringens (Cp) in the caeca and on performance of broiler chickens were tested in 2 experiments. The supplements were fed as single feed additives or in some combinations. No clinical signs or lesions caused by coccidia were observed in any of the studies. All supplements had an antibacterial effect on Cp and improved growth rate significantly. Carcass yield of birds fed growth promoters avilamycin or avoparcin was significantly higher compared with birds fed anticoccidials. These data indicate that, what concerns bird performance, during good hygienic conditions supplementation with antibiotic growth promoters may not be necessary when the diet is supplemented with an anticoccidial with antibacterial effects.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Cecum; Chickens; Clostridium Infections; Clostridium perfringens; Coccidiostats; Glycopeptides; Growth Substances; Ionophores; Lactones; Monensin; Oligosaccharides; Poultry Diseases; Pyrans; Random Allocation

A method is presented for the simultaneous determination of the three ionophores, monensin, salinomycin and narasin in muscle, liver and eggs from domestic fowl. Samples are homogenised in methanol and any ionophores present are extracted into toluene-hexane. The extracts are concentrated and injected into a bench-top electrospray LC-MS system. Chromatography is carried out using an end-capped reversed-phase column, with a mobile phase consisting a mixture of acetonitrile, methanol, tetrahydrofuran, trifluoroacetic acid and water. Using single-ion monitoring, the ionophores can be detected down to the 1 ng/g level.

Topics: Animals; Anti-Bacterial Agents; Chickens; Chromatography, High Pressure Liquid; Eggs; Liver; Mass Spectrometry; Monensin; Muscles; Pyrans; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution

Streptococcosis is a major disease of several fish species in Australia, Japan and South Africa. The minimum inhibitory concentration of some ionophores (lasalocid, monensin, narasin and salinomycin) was determined in vitro for an Enterococcus-like species pathogenic for rainbow trout (Oncorhynchus mykiss) in Australia. Forty isolates of the fish pathogen were tested, together with control strains of Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and Streptococcus bovis ATCC 9809. The minimum inhibitory concentrations (MIC) of erythromycin, the drug of choice for controlling streptococcosis, ranged between 0.1 and 0.8 microgram/ml whereas the MIC values for the ionophores ranged between 0.2 and 1.5 micrograms/ml. Of the ionophores tested, narasin was the most inhibitory (0.2-0.4 microgram/ml), while monensin was the least inhibitory (0.4-1.5 micrograms/ml). Salinomycin was marginally more inhibitory (0.4-0.8 microgram/ml) than lasalocid (0.8 microgram/ml).

Topics: Animals; Anti-Bacterial Agents; Enterococcus; Erythromycin; Fish Diseases; Gram-Positive Bacterial Infections; Ionophores; Lasalocid; Microbial Sensitivity Tests; Monensin; Oncorhynchus mykiss; Pyrans

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.

Topics: Animals; Chickens; Coccidiosis; Coccidiostats; Monensin; Poultry Diseases; Pyrans

Topics: Animal Feed; Animals; Chickens; Coccidiosis; Eimeria; Monensin; Poultry Diseases; Pyrans

Topics: Animals; Chickens; Coccidiosis; Dose-Response Relationship, Drug; Eimeria; Monensin; Poultry Diseases; Pyrans

Four isolates of Eimeria tenella obtained from the field were partially resistant to monensin. This resistance was not lost after 10 passages in unmedicated chickens, indicating that it was stable. One of the four isolates was examined and found to be resistant also to narasin, salinomycin and lasalocid.

Topics: Animals; Chickens; Coccidiosis; Coccidiostats; Drug Resistance, Microbial; Eimeria; Ionophores; Lasalocid; Monensin; Poultry Diseases; Pyrans

Topics: Animal Feed; Chemical Phenomena; Chemistry; Chromatography, High Pressure Liquid; Furans; Monensin; Pyrans

Topics: Animal Feed; Anti-Bacterial Agents; Chromatography, Thin Layer; Furans; Lasalocid; Monensin; Pyrans

Free Eimeria tenella sporozoites were exposed to the anticoccidial ionophores monensin, lasalocid, narasin, or salinomycin for 4 hr at 40 C, whereupon the drugs were removed by dilution centrifugation and the parasites inoculated into cultures of chick kidney cells. Cultures were fixed and stained at 4 and 96 hr postinoculation to determine the effect of ionophore uptake by the extracellular sporozoites on invasion and development. Pretreatment with each of these antibiotics significantly reduced the number of intracellular sporozoites and dramatically inhibited asexual development. These effects were dose-dependent. Exposure of free (extracellular) sporozoites to monensin at 40 C caused a significant decline in the number of surviving organisms over time as compared to nontreated sporozoites. This response also appeared to be dose-dependent. Scanning and transmission electron microscopy revealed that the surface of the treated sporozoites was very irregular and the organisms often exhibited a gross swelling. These results indicated that free Eimeria tenella sporozoites may incorporate a potentially lethal concentration of the polyether ionophorous antibiotics and that a coccidiocidal activity may be expressed whether or not penetration of host's cells occurs.

Topics: Animals; Cells, Cultured; Chickens; Dose-Response Relationship, Drug; Eimeria; Furans; Ionophores; Kidney; Lasalocid; Monensin; Pyrans

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Anti-Bacterial Agents; Cations, Monovalent; Dinitrophenols; In Vitro Techniques; Ionophores; Lasalocid; Male; Mitochondria, Liver; Mitochondrial Swelling; Monensin; Pyrans; Rats; Valinomycin

The anticoccidial efficacy, host tolerance, and projected resistance development of the three polyether antibiotics, monensin, narasin, and lasalocid were compared. The efficacy of narasin against different coccidial strains was found to parallel that of monensin in as much as strains which were refractory to monensin were also refractory to narasin. In contrast, lasalocid easily controlled some strains which were not well controlled by either narasin or monensin and failed to control one strain readily controlled by these two antibiotics. In growing chicks, lasalocid at the projected use level of 75 p.p.m. and narasin at an efficacious level of 100 p.p.m. were both better tolerated than monensin at the recommended use level of 121 p.p.m. The frequency of mutants resistant to each of these polyether compounds was found to be less than 8.6 X 10(-9) per drug sensitive oocyst for one strain of Eimeria tenella. This corresponds to less than 0.036 and 0.148 as frequent as mutants of this strain resistant to glycarbylamide or to amquinate, respectively.

Topics: Animals; Anti-Bacterial Agents; Chickens; Coccidiosis; Drug Resistance; Feces; Female; Furans; Lasalocid; Male; Monensin; Mutation; Poultry Diseases; Pyrans