Efficacy of some anticoccidial drugs for treating coccidial enteritis of the common carp caused by Goussia carpelli (Apicomplexa: Eimeriidae)

In this study, nine anticoccidial drugs commonly used in poultry were tested for efficacy for the prevention and treatment of Goussia carpelli (Apicomplexa) infection in common carp (Cyprinus carpio L.). To establish experimental infection with G. carpelli, paratenic host oligochaetes of the genera Tubifex and Limnodrilus were infected with oocysts, and laboratory-cultured parasite-free common carp fingerlings were infected by feeding to them oligochaetes containing sporozoites. The anticoccidial drugs (amprolium, narasin, maduramicin, salinomycin Na, lasalocid Na, diclazuril, robenidine HCl, monensin Na and toltrazuril), mixed in the food of the fish in a dose of 200 mg/kg, were fed for 12 days. Common carp fingerlings fed diclazuril, lasalocid, robenidine HCl or maduramicin and killed on day 14 after exposure were free from infection, while other groups treated with amprolium, toltrazuril, monensin Na, narasin or salinomycin Na harboured oocysts in the mucus and epithelium of the gut.     

The effect of ionophore anticoccidial agents on coccidia isolated in field conditions 1984-1985

Out of six isolates of coccidia of the species Eimeria tenella, obtained in the years 1984 and 1985 on farms with a stationary occurrence of coccidiosis, five were found to have reduced sensitivity or resistance to monensin. Neither were these isolates sensitive to further monovalent ionophorous anticoccidials narasin and salinomycin. The bivalent ionophorous anticoccidial lasalocid controlled five isolates completely, but for one its effectiveness was reduced. An isolate obtained on a farm with long-term absence of coccidiosis was sensitive to all anticoccidial drugs.     

In vitro lactic acid inhibition and alterations in volatile fatty acid production by antimicrobial feed additives

Batch culture fermentations were used to determine the effects of avoparcin, lasalocid, monensin, narasin, salinomycin, thiopeptin, tylosin, virginiamycin, monensin + tylosin combination, and two new ionophore compounds (RO22-6924/004 and RO21-6447/009) on lactic acid and volatile fatty acid (VFA) production. Ruminal fluid from cattle fed a high alfalfa hay diet was incubated with glucose for 12 h in a buffered medium to determine the effect of antimicrobial compounds on lactic acid concentration. Fermentations treated with antimicrobial compounds had higher final pH and lower L(+) lactic acid concentration. Narasin and salinomycin were more inhibitory than other ionophore compounds. Monensin and tylosin in combination was more effective than monensin alone. Among the nonionophore compounds, avoparcin was the least effective and thiopeptin, tylosin and virginiamycin were extremely effective in reducing lactic acid concentration. Ruminal fluid from cattle fed a diet of alfalfa hay and grain (50:50) was incubated with a mixture of sugars, casein and urea for 12 h in a buffered medium to determine the effect of antimicrobial compounds on VFA production. Generally, total VFA concentration was not affected by antimicrobial compounds except RO22-6924/004, tylosin and virginiamycin, which caused a reduction at high concentrations. Tylosin, monensin and tylosin mixture, thiopeptin and virginiamycin at high concentrations (greater than 6.0 micrograms/ml) increased the acetate proportion. All compounds increased the molar proportion of propionate. Tylosin and virginiamycin at high concentrations (greater than 6.0 micrograms/ml) decreased the proportion of propionate. Monensin and tylosin in combination had no effect on propionate proportion. Among the compounds tested, narasin and salinomycin were the most effective in enhancing propionate proportion. Ionophore compounds were more inhibitory to butyrate production than the nonionophore compounds. Batch culture fermentations may be used to quantitate the relative efficacy of antimicrobial compounds to alter ruminal fermentation characteristics.     

The efficacy of anticoccidial products against Eimeria spp. in northern bobwhites

To determine whether chemotherapeutic compounds available for use in domestic poultry are effective at controlling coccidiosis in northern bobwhites (Colinus virginianus), we tested 13 chemotherapeutic anticoccidials including amprolium (250 parts per million [ppm]), clopidol (125 ppm), diclazuril (1 ppm and 2 ppm), decoquinate (30 ppm), lasalocid (120 ppm), monensin (90 ppm), narasin/nicarbazin (36/36 ppm), robenidine (33 ppm), roxarsone (50 ppm), sulfadimethoxine/ ormetoprin (125/75 ppm), salinomycin (60 ppm), semduramicin (25 ppm), and zoalene (125 ppm and 150 ppm). Three tests were conducted using two replicates of 10 birds each: Infected, unmedicated controls and medicated birds were challenged with 1 x 10(6) oocysts of a field isolate consisting primarily of Eimeria lettyae. Subsequently, we tested clopidol, lasalocid, salinomycin, diclazuril (1 ppm), and monensin against mixed-species field isolates containing E. lettyae, E. dispersa, E. colini, or all. Weight gain, gross intestinal lesions, severity of diarrhea, and feed conversion ratio (FCR) 6 days postinfection were recorded. Lesion score, as previously reported, was unreliable as a measure of severity of infection in comparison with weight gain, fecal scores, and FCR. Excellent to good efficacy was found in clopidol, decoquinate, diclazuril (1 ppm and 2 ppm), and in lasalocid, narasin and nicarbazin, robenidine, sulfadimethoxine/ormetoprin, and zoalene (150 ppm). Marginal protection was found using monensin, salinomycin, semduramicin, or a roxarsone/semduramicin combination. Amprolium, roxarsone, and zoalene (125 ppm) were ineffective at controlling coccidia. Two of the six isolates tested against diclazuril 1 ppm and clopidol demonstrated a high degree of resistance, but none of the six isolates was resistant to lasalocid. Four of the eight isolates showed mild to moderate, and moderate to high, resistance against monensin and salinomycin, respectively. These findings indicate that several available compounds are effective at controlling coccidiosis in bobwhites.     

Influence of dietary electrolyte balance, source of added potassium and anticoccidial agents on the performance of male broilers

1. The performance of 1680 male broiler chickens was measured from one to 42 d of age. They were given diets with three (125, 165 and 205 mEq/kg) electrolyte balances (sodium + potassium - chloride), two sources of added potassium (carbonate or sulphate) and two anticoccidial agents (90 mg/kg of either monensin or lasalocid). 2. The dietary treatments had no significant effects on the growth performance of broiler chickens in the starter phase. 3. In the finisher phase, the chickens given the diets containing lasalocid utilised food less efficiently that those given the diets containing monensin. 4. There were significant interactions between dietary electrolyte balance and source of added potassium on body weight gains and food:gain ratios in the finisher phase. In diets with an electrolyte balance of 205 mEq/kg, the inclusion of potassium sulphate instead of potassium carbonate increased body weight gains by 3.4% and reduced food:gain ratios by 4.6%. 5. The body weight gains of chickens given the finisher diets containing lasalocid and added potassium carbonate were reduced by 2.6% compared to those of chickens given the diets containing monensin or added potassium sulphate. 6. The litter moisture content was higher in pens with chickens on the diets with an electrolyte balance of 205 mEq/kg than on the diets with either 125 or 165 mEq/kg. Both lasalocid and potassium sulphate tended to increase the litter moisture content. 7. It may be concluded that the inclusion of 90 mg/kg of either monensin or lasalocid in broiler diets does not alter the balance of electrolytes required for optimum growth performance of broiler chickens.     

A survey of sensitivity to anticoccidial drugs in 60 isolates of coccidia from broiler chickens in Brazil and Argentina

Coccidia were isolated from 90 broiler farms in 15 poultry-producing areas in Brazil and Argentina. Sixty isolates were tested for sensitivity to 7 anticoccidial drugs. The common species were: a) Eimeria tenella, 47 isolates; b) E. maxima, 49 isolates; c) E. acervulina, 44 isolates; d) E. mitis, 26 isolates; and e) E. brunetti, 12 isolates. Isolates were considered sensitive to drugs if intestinal lesion scores of medicated broilers were reduced by at least 50% compared with unmedicated infected broilers or if weight gain was at least 75% of that of uninfected birds in a 6-day laboratory test. According to lesion scores, there was evidence of resistance or seriously reduced sensitivity to monensin in 20 isolates, narasin in 29, salinomycin in 11, maduramicin in 1, clopidol in 36, amprolium in 40, and nicarbazin in 1. According to broiler weight gain, there was resistance to monensin in 36 isolates, narasin in 32, salinomycin in 28, maduramicin in 2, clopidol in 28, amprolium in 50, and nicarbazin in 4. These results suggested incomplete cross resistance of coccidia to polyether ionophorous drugs. The degree of resistance might be explained by previous patterns of use of these drugs.     

Isolates of Eimeria tenella: studies on resistance to ionophorous anticoccidial drugs

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.     

Repurposing Ionophores as novel antimicrobial agents for the treatment of bovine mastitis caused by Gram‐positive pathogens

Increasing reports of multidrug‐resistant bacterial infections in animals has created a need for novel antimicrobial agents that do not promote cross‐resistance to critically important antimicrobial classes used in human medicine. In response to the recent emergence of antimicrobial resistance in several bovine mastitis pathogens, in vitro antimicrobial susceptibility was determined for four polyether ionophores (lasalocid, monensin, narasin and salinomycin) against Staphylococcus spp. and Streptococcus spp. isolated from clinical cases. In addition, erythrocyte haemolysis and WST ‐1 cell proliferation assays were used to assess in vitro mammalian cell cytotoxicity and biofilm susceptibility testing was performed using the minimum biofilm eradication concentration (MBEC ?) biofilm assay. Lasalocid, monensin, narasin and salinomycin exhibited bacteriostatic antimicrobial activity against all pathogens tested, including methicillin‐resistant staphylococci, with MIC ₉₀ values <16 μg/ml. Narasin and monensin displayed the least toxicity against mammalian cell lines and all compounds significantly reduced viable cell numbers in a Staphylococcus aureus biofilm. Based on in vitro characterization, all four ionophores offer potentially novel treatments against bovine mastitis but in vivo studies will be essential to determine whether acceptable safety and efficacy is present following intramammary administration.     

Anticoccidial evaluation of halofuginone, lasalocid, maduramicin, monensin and salinomycin

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).     

Response of 21 Canadian field isolates of chicken coccidia to commercial anticoccidial drugs

Coccidia were isolated from 30 broiler farms in major poultry-producing provinces of Canada; 21 mixed-species isolates were tested for sensitivity to anticoccidial drugs. Eimeria acervulina was identified in 20 samples, E. maxima in 15, and E. tenella in 10 of the mixed-species isolates. On the basis of weight gain after infection, 3 isolates were judged sensitive to amprolium, 5 to monensin, 9 to salinomycin, 14 to lasalocid, 19 to halofuginone, and 20 to nicarbazin. Similar trends in sensitivity/tolerance were identified from the percent reduction of intestinal lesion scores of medicated birds compared with scores of unmedicated, infected controls. These results were consistent with the previous pattern of use of anticoccidial drugs in commercial poultry in Canada.     

三种药物防治奶牛球虫病试验

目的为考察现有抗球虫药物对奶牛球虫病的防治效果。方法选用应用较广的3种抗球虫药物(地克珠利、拉沙里菌素、莫能菌素)对1~6月龄球虫感染阳性奶牛进行防治试验。将34头球虫感染阳性奶牛分为4组,地克珠利组9头,按体重0.5 mg/kg.BW每天口服1次;拉沙里菌素组9头,按360 mg/头每天口服1次;莫能菌素组8头,按1 mg/kg.BW每天口服1次;不用药物对照组8头。连续用药10d,停药后再观测10 d,每3 d直肠采集粪便检测球虫1次,以每克粪便球虫卵囊数(OGP)为试验指标。结果用药9 d后的OPG与用药前相比,地克珠利组下降了78.9%,拉沙里菌素组下降了80.92%,莫能菌素组下降了98.81%。停药3~6 d后,地克珠利和拉沙里菌素组的OPG上升较快,而莫能菌素组的OPG保持较低水平。结论3种抗球虫药对奶牛球虫病均有防治效果,其中莫能菌素最好,拉沙里菌素和地克珠利次之。     

In-vitro antimicrobial susceptibility of Clostridium perfringens from commercial turkey and broiler chicken origin

The minimum inhibitory concentrations (MIC) of eight antibiotics and two anticoccidial agents were determined for Clostridium perfringens strains isolated from 26 commercial broiler farms and 22 commercial turkey farms. Isolates were obtained from the intestines of birds on the farm or at the processing plant using standard culture and identification techniques. The microbroth dilution test was used to determine the MIC for each compound. Most isolates from chickens had MICs in the range of 2–16 mg/L for tilmicosin, tylosin and virginiamycin, whereas the MICs for avilamycin, avoparcin, monensin, narasin and penicillin were ≤1 mg/L. Most strains from chickens had high MICs (≥64 mg/L) and appeared to be resistant to bacitracin and lincomycin. Most turkey isolates had MICs in the range of 2–16 mg/L for bacitracin, tilmicosin, tylosin and virginiamycin, with strains exhibiting MICs ≤ 1 mg/L for avilamycin, avoparcin, monensin, narasin and penicillin. Several turkey isolates had MICs ≥ 64 mg/L to lincomycin. No attempt was made to associate farm usage of a particular antibiotic to the antibiograms.     

柔嫩艾美耳球虫对四种抗球虫药的交叉抗药性试验

为了测试柔嫩艾美耳球虫的４种抗药虫株（抗地克珠利、抗拉沙里菌素、抗盐霉素和抗克球粉虫株）对４种抗球虫药（地克珠利、拉沙里菌素、盐霉素和克球粉）的敏感性进行了本试验。结果表明：柔嫩艾美耳球虫地克珠利抗药虫株对拉沙里菌素、盐霉素和克球粉均表现敏感,拉沙里菌素抗药虫株、盐霉素抗药虫株和克球粉抗药虫株对地克珠利也表现为高度敏感,因此,柔嫩艾美耳球虫对地克珠利与拉沙里菌素、地克珠利与盐霉素、地克珠利与克球粉３组药物不存在交叉抗药性。     

Sensitivity of field isolates of Eimeria species to monensin and lasalocid in the chicken

Isolates of Eimeria species obtained from broiler or from breeder farms were compared for their sensitivity to two ionophorous anticoccidial drugs, monensin and lasalocid. All of 25 isolates from broiler farms were resistant to 100 ppm monensin or 90 ppm lasalocid, while 14 of 16 isolates were resistant to monensin and seven of 16 to lasalocid from breeder farms (replacement layer and broiler breeder).     

Effect of ionophore antibiotics on experimentally induced lactic acidosis in cattle

Salinomycin, a new ionophore antibiotic, was tested and compared with lasalocid and monensin for preventing experimentally induced lactic acidosis. Five rumen-fistulated adult cattle were used in a 5 X 5 Latin square design, and the treatments were as follows: no treatment (control), 0.11 mg of salinomycin/kg of body weight (S1), 0.22 mg of salinomycin/kg (S2), 0.66 of lasalocid/kg, and 0.66 mg of monensin/kg. Acidosis was induced by intraruminal administration of a ground corn-corn starch mixture (50:50, 12.5 g/kg) once a day for up to 4 days. Antibiotics were administered along with grain-starch mixture. Rumen and blood samples were obtained before and at 6, 12, and 24 hours after each carbohydrate-antibiotic dosing to monitor acid-base status. Control and S1-treated cattle became ruminally acidotic within 54 hours, whereas cattle treated with S2, lasalocid, and monensin resisted acidosis for up to 78 hours after dosing. Cattle treated with S2, lasalocid, or monensin had higher rumen pH and lower L(+)- and D(-)-lactate concentrations than did control or S1-treated cattle. Rumen pH decrease to below 5.0 in S2-, lasalocid-, and monensin-treated cattle was not due to lactic acid, but to increased production of volatile fatty acids. Rumen propionate proportion increased initially in antibiotic-treated cattle, but after 48 hours, butyrate proportion increased significantly. Despite low rumen pH and high lactate concentration, lacticacidemia was not evident, and the systemic acid-base disturbance was mild in control cattle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interaction of T-2 fusariotoxin and monensin in broiler chickens infected with Coccidia

Field observations suggest that coccidiosis is a common cause of death in broiler chicken flocks fed diets containing sufficient amounts of ionophore antibiotics (monensin, narasin, etc.) and contaminated with mycotoxins, particularly with T-2 fusariotoxin. To study this phenomenon, broiler chickens fed diets containing different amounts of T-2 toxin and free from monensin, or containing a preventive dose (100 mg/kg of feed) of monensin, were infected experimentally with coccidian oocysts. In all groups fed a diet containing monensin plus T-2 toxin severe clinical symptoms of coccidiosis (blood-stained faeces etc). occurred. Deaths and retarded growth depended on the toxin dose and were considerable. The body mass gain of chicks fed a diet containing monensin and T-2 toxin but not infected with coccidia was inferior to that of groups fed diets which contained either monensin or T-2 toxin (experiment 2). On the basis of these findings a negative interaction of the two compounds is assumed. This seems to be supported by the results of experiment 3, i. e. the finding that the lethal dose of narasin, a compound closely related to monensin both in chemical structure and mechanism of action, proved to be much lower (LD50 = 102 mg/kg body mass) for chickens fed a diet supplemented with T-2 toxin than for the control chickens (LD50 = 176 mg/kg body mass). The present results suggest that the feeding of diets severely contaminated with T-2 toxin may alter the anticoccidial efficacy of monensin.     

In vitro efficacy and pharmacodynamic profiles of four polyether ionophores against methicillin-resistant Staphylococcus spp.

The objective of this study was to determine the minimum inhibitory concentrations (MICs) and pharmacodynamic profiles of four ionophores (lasalocid, monensin, narasin and salinomycin) against staphylococcal isolates from clinical cases of human and veterinary staphylococcal infections, and to determine the effect of methicillin resistance on the antimicrobial activity of ionophores. Broth microdilution MIC testing was used to determine antimicrobial activity against 156 staphylococcal isolates of human and veterinary origin. Pharmacodynamic profiles were examined using time-kill kinetics profiles against an ATCC type strain of Staphylococcus aureus and a clinical isolate of methicillin-resistant Staphylococcus pseudintermedius. All tests were performed in accordance with CLSI guidelines. All four ionophores demonstrated antimicrobial activity against methicillin-resistant staphylococci at concentrations similar to those observed for methicillin-susceptible isolates of the same species. Testing of human and veterinary MRSA isolates also showed that MIC values were not influenced by the host origin of the isolates. Pharmacodynamic profiles were similar for both isolates tested across all four ionophores, with similar reductions in viable cell counts being observed over an 18- to 24-hr period. Lasalocid, monensin, narasin and salinomycin all demonstrated antimicrobial activity against staphylococcal isolates of human and veterinary origins, with activity being unaffected by methicillin resistance status, although some Staphylococcus species-specific effects were observed that require further investigation.     

Isolation and selection of ionophore-tolerant Eimeria precocious lines: E. tenella, E. maxima and E. acervulina

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.     

What has happened in norway after the ban of avoparcin? Consumption of antimicrobials by poultry

When avoparcin was prohibited for use as feed additive in poultry in Norway on 31 May 1995, an increased incidence of Clostridium perfringens-associated necrotic enteritis (NE) and an increase in the use of antibacterial (AB) drug therapy in meat-type poultry was expected. The consumption of AB drugs for use against NE in poultry in the period 1990-2001 was investigated by use of sales statistics at the drug-wholesaler level. Defined daily dose (DDD) per kg live weight poultry was the unit of measurement for drug use (to correct for differences in the dosages). Sales figures of the AB drugs were converted to number of DDDpoultry sold for the numbers of broilers at risk (broilers were 97% of the slaughter poultry). Estimated annual percentages of the broilers treated against NE increased abruptly after the avoparcin ban--but in 1996, this figure declined to the same level as before the ban and has remained at that low level since then. In November 1995, narasin was approved temporarily as an ionophore feed additive (IFA) in broilers. The usage patterns of IFAs in broilers were measured as the weight of feed to which an IFA was added per broiler chicken produced. In 1996-2001, the IFAs used in broilers were predominantly narasin. We note that the temporary increase in NE after the avoparcin ban coincide with the period before narasin became available. The increase in the consumption of AB drugs for the treatment of NE in poultry following the avoparcin ban has been negligible.     

Effect of including lasalocid or monensin singly or in combination with furazolidone on the growth and feed consumption of turkey poults

Lasalocid and monensin are widely used to control coccidiosis in broilers, but not in turkey poults. Four feeding trials were conducted to determine the performance of turkey poults when these compounds were used singly or in combination with 100 ppm of furazolidone. Bodyweights and feed consumption were significantly depressed for five weeks after hatching by 150 ppm of lasalocid. Combining furazolidone with lasalocid ameliorated the toxic effect of lasalocid. Bodyweights were significantly depressed by 150 ppm of monensin in the fifth week after hatching, but there was no significant depression in feed consumption. Furazolidone exacerbated any toxic effects of monensin. Data indicate that monensin may be used safely at dosages greater than the recommended level of 60 to 99 ppm, but should not be used in combination with furazolidone.