monensin and maduramicin

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

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

Drug-drug interactions (DDIs) may adversely affect the prevention and cure of diseases. The effects of three polyether ionophore antibiotics, salinomycin (SAL), monensin (MON), and maduramycin (MAD) on the pharmacokinetics of florfenicol (FFC) were investigated in broilers. The chickens were fed rations with or without SAL (60 mg/kg feeds), MON (120 mg/kg feeds), or MAD (5 mg/kg feeds) for 14 consecutive days. FFC was given to the chickens either intravenously (i.v.) or orally (p.o.) at a single dose of 30 mg/kg body weight. Blood samples were taken from each chicken at 0-24 h postadministration of FFC. The plasma concentration of FFC was detected by high-performance liquid chromatography. The plasma concentration of FFC decreased with i.v. or p.o. co-administration of SAL, MON, or MAD in broilers, implying occurrence of DDIs during the co-administration of FFC with these ionophores. Our findings suggest that more attention should be given to the use of FFC to treat bacterial infections in chickens supplemented with polyether ionophore antibiotics.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Chickens; Chromatography, High Pressure Liquid; Coccidiostats; Drug Interactions; Drug Therapy, Combination; Injections, Intravenous; Ionophores; Lactones; Male; Monensin; Pyrans; Thiamphenicol

The effects of ionophore antibiotics on the enzyme activity, protein and mRNA expression levels of cytochrome P450 (CYP) isoenzymes were investigated in liver from male Arbor Acres (AA) broiler chicks. Monensin, salinomycin and maduramycin at the dosage of 120, 60, and 5 mg/kg were administered in feed for 14 days. CYP1A and CYP3A activities were quantitated using cocktail probe drugs and a high performance liquid chromatographic (HPLC) assay at the 15th day; the protein expressions of CYP1A and CYP3A were detected by Western blot. CYP1A4, CYP1A5 and CYP3A37 mRNA levels were detected by real-time polymerase chain reaction (real-time PCR). Monensin, salinomycin and maduramycin had no effect on caffeine metabolism, protein expression and mRNA expression, but did induce dapsone metabolism, increasing CYP3A protein expression. However, there was no change in CYP3A37 mRNA expression as compared with the control group. It is suggested that ionophore antibiotics may have an induction effect on CYP3A expression and enzyme activity and that such effect might be related to the posttranscriptional regulation of its protein expression. Consideration of the enhanced metabolism of other drugs used simultaneously with ionophores is therefore recommended.

Topics: Animals; Blotting, Western; Caffeine; Chickens; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP3A; Dapsone; Dose-Response Relationship, Drug; Gene Expression; Ionophores; Lactones; Liver; Male; Microsomes, Liver; Monensin; Pyrans; Reverse Transcriptase Polymerase Chain Reaction; RNA Processing, Post-Transcriptional; RNA, Messenger

Drug resistance in coccidial populations has been a major problem to the prophylactic chemotherapy. Nevertheless, the mechanisms of the resistance are still poorly understood. In this report, cDNA array was designed based on the cDNA library for analysis of gene expression profile of the drug-resistant lines and their sensitive parental lines of Eimeria tenella. Two thousand eight hundred and six ESTs (expressed sequence tags) were obtained from 9600 clones which were randomly derived from the cDNA library with the 3' end sequencing. A total of 1424 TUTs (tentative unique transcripts) were determined from the database of our ESTs by bioinformatics analysis, from which a cDNA array was developed. The comparison of monensin-resistant line (MonR) and maduramicin-resistant line (MadR) with their sensitive parental lines was undertaken independently. It was observed that the number of the up-regulated genes was 5.58-fold more than that of the down-regulated genes in MonR when compared with its parental line. The up-regulated genes were mainly involved in cytoskeletal rearrangements and energy metabolism. In MadR, the number of the down-regulated genes was 3.07-fold more than the up-regulated genes, which were mainly related to invasion and cytoskeletal genes. However, in MadR the level of the glycometabolism-related and potential transporter genes were reduced. Our data suggest that the mechanisms of monensin and maduramicin resistance of E. tenella might be a very complex process.

Topics: Animals; Cecum; Chickens; Coccidiosis; Coccidiostats; DNA Primers; DNA, Complementary; Drug Resistance; Eimeria tenella; Expressed Sequence Tags; Gene Library; Ionophores; Lactones; Monensin; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; RNA, Helminth

Eimeria parasites were isolated from Nanhai Guangdong province (southern China) and studied in chickens in wire cages to evaluate their drug resistance against commonly used ionophores: monensin (100 mg/kg of feed), lasolacid (90 mg/kg), salinomycin (60 mg/kg), maduramicin (5 mg/kg) and semduramicin (25 mg/kg). Chinese Yellow Broiler Chickens were infected with 40,000 crude sporulated Eimeria oocysts at 15 days of age and prophylactic medication commenced a day prior to infection. Drug resistance was assessed for each ionophore drug by calculating the anticoccidial index (ACI) and percentage optimum anticoccidial activity (POAA) based on relative weight gain, rate of oocyst production and lesion values. Results revealed that Nanhai Eimeria oocysts comprising of E. tenella, E. maxima and E. acervulina, were resistant to monensin, sensitive to both salinomycin and lasolacid and partially sensitive to maduramicin and semduramicin. By selection for early development of oocysts during passage through chickens, the prepatent time of E. tenella, E. maxima and E. acervulina were reduced by 49, 36 and 22 h, respectively. The precocious lines are less pathogenic than the parent strains from which they were selected and conferred a satisfactory protection for chickens against coccidiosis. These ionophore-tolerant precocious lines could have wider applications in the development of anticoccidial vaccines for sustainable control of coccidiosis.

Topics: Animals; Chickens; Coccidiosis; Coccidiostats; Drug Resistance; Eimeria; Eimeria tenella; Ionophores; Lactones; Lasalocid; Monensin; Nigericin; Oocysts; Parasitic Sensitivity Tests; Poultry Diseases; Pyrans; Random Allocation; Treatment Outcome

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

Ten Eimeria field isolates from North Germany were studied in battery tests for sensitivity to selected anticoccidials. A high percentage of the Eimeria field isolates (9 out of 10) showed resistance to anticoccidials, mostly multiple resistance. Partial or complete resistance to maduramicin was found in 7 field isolates, to monensin in 6, to salinomycin in 5, to nicarbazin in 8, to halofuginone in 7, to robenidine and toltrazuril in 1, and to diclazuril in 2 field isolates. Multiple resistance had developed in 7 of the 10 isolates. Cross-resistance between maduramicin, monensin, and salinomycin occurred in 5 Eimeria isolates. One isolate showed cross-resistance between diclazuril and toltrazuril. From the resistant isolates 15 pure E. acerculina and 5 pure E. brunetti strains were obtained by single oocyst infections. Seven of the E. acerculina and 4 of the E. brunetti strains showed resistance or partial resistance that was also present in the original isolate. Ten of 11 resistant strains were multiply resistant.

Topics: Animals; Chickens; Coccidiosis; Coccidiostats; Drug Resistance; Drug Resistance, Multiple; Eimeria; Germany; Lactones; Male; Monensin; Nicarbazin; Nitriles; Piperidines; Poultry Diseases; Pyrans; Quinazolines; Quinazolinones; Robenidine; Triazines

A rifampicin-resistant Lactobacillus salivarius 51R was administered orally to newly hatched broiler chickens. The resistance to rifampicin enabled us to differentiate the organism administered from indigenous strains. One day after inoculation, Lactobacillus salivarius 51R dominated among lactobacilli in the crop and caeca of all inoculated chickens, even in those ones receiving maduramicin and monensin at 5 and 100 mg per kg of feed mixture, respectively. Coliform counts in both crop and caeca of inoculated chickens were significantly lowered on the first day after treatment. Also, counts of the crop enterococci were decreased in inoculated chickens. Rifampicin-resistant lactobacilli were still present in high numbers in the crop and caecal contents of inoculated chickens sampled 5 days after inoculation. Differences in counts of total lactobacilli, coliform bacteria, and enterococci were mostly nonsignificant in these samples. Our results demonstrate that (i) bacterial counts in the chicken gut were influenced by probiotic Lactobacillus administration, and (ii) chicken lactobacilli are resistant to ionophore coccidiostats under in vivo conditions.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Antitubercular Agents; Cecum; Chickens; Coccidiostats; Crop, Avian; Drug Combinations; Drug Resistance, Microbial; Enterobacteriaceae; Enterococcus; Lactobacillus; Lactones; Monensin; Rifampin; Time Factors

The tolerance of chickens to monensin (12.5 mg/kg of feed) and maduramicin (3.0 mg/kg of feed) fed at a reduced dose in the presence of the antioxidant duokvin was studied in two experiments including 2 x 200 Tetra-82 broiler chickens. Tolerance was assessed by the appearance of clinical signs indicative of a toxic effect, the number of deaths, the groups' body weight gain, feed and drinking water intake, the aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities, calcium ion, inorganic phosphate and total protein content of the blood plasma, the haematocrit value, and haemoglobin concentration. When applied at a dose that had proved to be optimum in the efficacy studies, neither the monensin-duokvin combination (12.5 mg monensin per kg of feed + 120 mg duokvin per kg of feed) nor the maduramicin-duokvin combination (3.0 mg maduramicin per kg of feed + 120 mg duokvin per kg of feed) exerted a statistically significant influence on the parameters tested.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Antioxidants; Chickens; Coccidiostats; Drug Combinations; Drug Synergism; Ionophores; Lactones; Male; Monensin; Quinolines

Two trials were carried out on a total of 2 x 360 Tetra-82 broiler chickens to study how the presence of the antioxidant duokvin as potentiating agent influenced the compatibility of reduced doses of monensin (12.5 mg/kg of feed) or maduramicin (3.0 mg/kg of feed) with other chemotherapeutic agents (tiamulin, erythromycin, sulfaquinoxaline, sulfachlorpyrazine, flumequine, tylosin, kitasamycin) widely used in broiler rearing. Compatibility was assessed on the basis of the appearance of clinical signs suggestive of toxic interaction, the mortality rate, body mass gain, feed consumption and drinking water intake, and changes in AST and LDH activities of the blood plasma. The monensin-duokvin combination (12.5 mg monensin/kg of feed + 120 mg duokvin/kg of feed) was found to be compatible with erythromycin, sulfaquinoxaline, sulfachlorpyrazine, flumequine, tylosin and kitasamycin. For tiamulin, a slight incompatibility was observed; however, this was much less severe than that found for monensin administered at a dose of 100 mg/kg of feed. The maduramicin-duokvin combination (3.0 mg maduramicin/kg of feed + 120 mg duokvin/kg of feed) was compatible with all the compounds tested; thus, it can be safely applied also in combination with tiamulin.

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Chickens; Coccidiostats; Drug Combinations; Drug Synergism; Ionophores; Lactones; Male; Monensin; Quinolines

In two experiments, the compatibility of the anticoccidial combinations of monensin and duokvin, as well as that of maduramicin and duokvin, with some antimicrobials widely used in the broiler production was studied in cockerels. The monensin-duokvin combination was found to be fully compatible with erythromycin, sulphachlorpyrazine, and sulphaquinoxaline. With tiamulin, a slight interaction was observed, but it was far less severe than the toxic interaction between monensin and the diterpene antibiotic. The maduramicin-duokvin combination proved to be compatible with all of the chemotherapeutics tested, including tiamulin. The results of the studies indicate that the adverse interactions of monensin and maduramicin with certain antimicrobials can be considerably diminished or even abolished by using them in reduced doses in combination with the dihydroquinoline compound duokvin.

Topics: Animals; Anti-Infective Agents; Chickens; Coccidiostats; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Ionophores; Lactones; Male; Monensin; Quinolines

The efficacy of semduramicin (AVIAX), a novel polyether ionophore, was profiled in a series of 57 battery tests conducted in the United States and the United Kingdom. The studies employed mixed and monospecific infections of Eimeria acervulina, Eimeria mivati/Eimeria mitis, Eimeria brunetti, Eimeria maxima, Eimeria necatrix, and Eimeria tenella derived from North American and European field isolates. Ten-day-old broiler cockerels in pens of 8 to 10 birds were continuously medicated in feed beginning 24 h before challenge in tests of 6 to 8 days' duration. At the use level of 25 ppm, semduramicin effectively controlled mortality, lesions, and weight gain depression that occurred in unmedicated, infected controls for all species. In comparison with 60 ppm salinomycin, semduramicin significantly (P < .05) improved weight gain against E. brunetti and E. tenella, lesion control against E. brunetti and E. maxima, and the control of coccidiosis mortality against E. tenella. Salinomycin was superior (P < .05) to all treatments in maintenance of weight gain and control of lesions for E. acervulina. Maduramicin at 5 ppm was inferior (P < .05) to semduramicin in control of E. acervulina and E. maxima lesions, but was superior (P < .05) to all treatments in maintenance of weight gain and control of lesions in E. tenella infections. The data indicate that semduramicin at 25 ppm is well tolerated in broilers and possesses broad spectrum anticoccidial activity.

Topics: Animals; Anti-Bacterial Agents; Chickens; Coccidiosis; Eimeria; Lactones; Male; Monensin; Nigericin; Poultry Diseases; Pyrans; Species Specificity; Treatment Outcome; Weight Gain

The activities of five anticoccidials were compared against Eimeria species in/of chickens, in controlled in vivo and in vitro laboratory studies. Two more recent and potent market entries (maduramicin and halofuginone) were compared with three older polyether antibiotic anticoccidials (monensin, lasalocid and salinomycin). Halofuginone, lasalocid, maduramicin, monensin and salinomycin were evaluated at 3, 125, 5, 120 and 66 ppm, respectively, of active drug in the diets. At these levels, all five drugs demonstrated significant activity against Eimeria tenella, E. maxima, E. necatrix, E. brunetti and E. acervulina (in vivo). Monensin was least effective against E. tenella, and one of the lesser efficacious drugs against E. necatrix, maduramicin, was least effective against E. maxima. In studies of single Eimeria species infections, comparable weight gains were noted for the drugs. In the mixed Eimeria species infections, however, birds treated with maduramicin had significantly higher weight gains than did birds medicated with monensin. Unlike in vivo potencies, titration in vitro indicated that monensin was most potent (active at 10(-6) mcg ml-1), and maduramicin and lasalocid least potent (inactive at less than or equal to 10(-3) mcg ml-1).

Topics: Animals; Anti-Bacterial Agents; Body Weight; Chickens; Coccidiosis; Coccidiostats; Eimeria; Female; Ionophores; Lactones; Lasalocid; Male; Monensin; Piperidines; Poultry Diseases; Pyrans; Quinazolines; Quinazolinones