Effect of forage quality and narasin inclusion on ruminal fermentation, nutrient intake, and total tract digestibility of Nellore steers.

The study aimed to evaluate the effects of forage quality and narasin inclusion on intake, digestibility, and ruminal fermentation of Nellore steers. Twenty-eight rumen-cannulated Nellore steers (initial body weight [BW] = 350 ±â€…32.4 kg) were allocated to individual pens in a randomized complete block design, with 7 blocks, defined according to the fasting BW at the beginning of the experiment. The steers were randomly assigned within blocks to 1 of 4 experimental diets in 2 × 2 factorial arrangements, being the first-factor forage quality (MEDIUM = 81 g of CP/kg of dry matter [DM], and HIGH = 153 g of CP/kg of DM), and the second factor was the inclusion (N13 = diet plus 13 mg/kg of DM of narasin) or not (N0) of narasin (Zimprova; Elanco Animal Health, São Paulo, Brazil). The experiment consisted of a 28-d period with 22 d for adaptation and the last 6 d for data collection. No haylage quality × narasin interaction (P ≥ 0.68) was observed on DM and nutrient intake. Haylage quality affected (P ≤ 0.01) DM intake, with greater values observed for steers fed HIGH compared with MEDIUM haylage. There was an increase (P < 0.001) in OM, NDF, hemicellulose, and CP intake for steers consuming HIGH vs. MEDIUM haylage. Including N13 did not affect (P > 0.39) DM and nutrient intake of steers. No haylage quality × narasin interactions were detected (P ≥ 0.60) for total tract nutrient digestibility. However, steers fed with HIGH haylage showed an increase (P > 0.001) in DM and digestibility of all nutrients compared with MEDIUM. Steers fed a MEDIUM haylage had a greater (P < 0.01) proportion of acetate compared with steers fed HIGH during all evaluated hours. Steers fed HIGH haylage had a greater (P < 0.01) proportion of propionate at 0 h compared with steers consuming MEDIUM, whereas at 12 h, steers consuming MEDIUM hay had a greater (P < 0.01) proportion of propionate vs. HIGH haylage. A haylage quality × narasin and haylage quality × time of collection interactions were detected (P ≤ 0.03) for rumen ammonia concentration, which was reduced (P < 0.03) in N13 vs. N0 steers consuming HIGH haylage. Collectively, high-quality haylage allows increased consumption and digestibility, with more energy-efficient ruminal fermentation. In addition, narasin might be an important nutritional tool in forage-based diets to enhance the ruminal fermentation parameters of Bos indicus Nellore steers.

A meta-regression analysis to evaluate the effects of narasin on grow-finish pig performance.

Ionophores are feed additives that decrease gram-positive microbial populations by disrupting the ion transfer across cell membranes resulting in improved growth performance. Narasin (Skycis; Elanco Animal Health, Greenfield, IN) is an FDA-approved ionophore utilized for increased rate of weight gain and improved feed efficiency in growing-finishing pigs. A meta-regression analysis was conducted to evaluate the effects of added narasin in growing-finishing pig diets to predict its influence on average daily gain (ADG), feed efficiency (G:F), and carcass yield. A database was developed containing 21 technical reports, abstracts, and refereed papers from 2012 to 2021 representing 35 observations for growth performance data in studies ranging from 35 to 116 d in length (overall data). In addition, within these 35 observations, individual period data were evaluated (143 observations) using weekly, bi-weekly, or monthly performance intervals (period data). Regression model equations were developed, and predictor variables were assessed with a stepwise manual forward selection procedure. The ADG model using the overall data included ADG, ADFI, and G:F of the control group, added narasin dose, and narasin feeding duration categorized as longer or shorter than 65 d. Predictor variables included in the G:F model using overall data were ADG, ADFI, and G:F of the control group and added narasin dose. For carcass yield, the final model included ADFI and G:F of the control group, added narasin dose, and narasin feeding duration of longer than 65 d. In the period model for ADG, the predictors included ADG, ADFI, and G:F of the control group, added narasin dose, and average BW of the control group categorized into greater than or less than 105 kg. For period data for G:F, the model selected ADG, ADFI, and G:F of the control group and added narasin dose. Based on the results, the overall response to added narasin for ADG and G:F was quadratic and tended to decrease as ADG and G:F increased. A similar quadratic response was observed for the individual period data. In summary, using median values from the database for predictor variables, this meta-analysis demonstrated narasin would be expected to improve ADG between 1.06% and 1.65%, G:F between 0.71% and 1.71%, and carcass yield by 0.31% when fed continuously for longer than 65 d.

Supplementing narasin or monensin to control coccidiosis in naturally infected calves.

This experiment compared narasin and monensin as anticoccidials for calves naturally infected with Eimeria spp. Twenty-four weaned, non-castrated male calves (Bos indicus × B. taurus cross) were assigned to this experiment (days -8 to 42). All calves were infected by Eimeria spp. according to oocyst count per gram (OPG) from fecal samples collected on days -8 and -7 (average 1,059 ±â€…101 oocysts/g). Calves were housed in individual pens, received corn silage, mineral mix, and water for ad libitum consumption, in addition to a grain-based supplement at 200 g/head daily. Fecal samples were collected on days -2 and -1 for OPG, and results averaged as initial OPG value. Calves were blocked according to initial OPG into eight blocks of three calves each, ranked within each block according to body weight (BW) recorded on day -1, and assigned to receive narasin (NAR; 0.8 mg/kg of BW), monensin (MON; 1 mg/kg of BW), or no ionophore (CON; negative control). Ionophores were added to the grain-based supplement, and offered from days 0 to 42 of the experiment. Calf BW was recorded on days 7, 14, 21, 28, 35, and 42. Fecal samples were collected on days 6 and 7, 13 and 14, 20 and 21, 26 and 27, 34 and 35, and 41 and 42 for OPG analysis, and results from samples collected on consecutive days were averaged. Aliquoted fecal samples were also pooled across calves from the same treatment and collection days, and used to determine the prevalence of individual species of Eimeria. No treatment effects were detected (P ≥ 0.51) for calf BW or growth rate. A treatment × day interaction was detected (P < 0.01) for OPG, as NAR and MON calves had less (P < 0.01) OPG compared with CON calves beginning on day 7. The OPG was also less (P ≤ 0.03) in MON compared with NAR calves on days 7, 14, and 28, but did not differ (P ≥ 0.48) on days 21, 35, and 42. The anticoccidial efficacy of NAR and MON did not differ (P ≥ 0.16) when calculated across all Eimeria spp., or according to prevalence of E. bovis and E. alabamensins. A treatment × day interaction was detected (P = 0.04) for anticoccidial efficacy to E. alabamensis, which was greater (P < 0.01) in MON calves on days 7 and 14 and did not differ (P ≥ 0.40) afterward. Collectively, both ionophores were similarly effective in controlling coccidiosis upon completion of the 42-d study, although the anticoccidial effects of monensin were noted earlier in the experiment. Nonetheless, these results corroborate narasin as an efficient anticoccidial ionophore for naturally infected calves.

Hatchery Losses in Flocks of Layer and Broiler Breeders Due to Feed Contamination with Nicarbazin and Narasin: A Case Report.

In the current study, we investigated decreased hatchability and increased embryonic mortality in two farms of layer breeders (flocks A1 and B1) and a farm of broiler breeders (flocks C1 and C2) from Austria, which also presented discoloration of eggshells in 2% of the eggs. After conducting clinical evaluations and the approval that the feed operator was common for flocks A1 and B1, and C1 and C2, it was decided to investigate the feed. Our findings revealed that the feed contained levels of nicarbazin and narasin up to five and 14 times, respectively, above the maximum limits allowed by the European Union for nontarget species. On the other hand, there were no significant abnormalities in vitamin levels, which were also described as the etiology of the noticed abnormalities. Switching to a noncontaminated feed resulted in the clinical signs and production parameters returning to expected ranges. This report emphasizes the significance of considering feed contamination by nicarbazin and narasin as a potential cause of hatchery losses in nontarget species, even in the absence of other clinical signs.

Reporte de caso- Pérdidas en la eclosión de parvadas de reproductoras ponedoras y pollos de engorde debido a la contaminación del alimento con nicarbazina y narasina: Reporte de un caso. En el presente estudio, se investigó la disminución de la incubabilidad y el aumento de la mortalidad embrionaria en dos granjas de reproductoras ponedoras (parvadas A1 y B1) y una granja de reproductoras de pollos de engorde (parvadas C1 y C2) de Austria, que también presentaron decoloración del cascarón en el 2% de los huevos. Luego de realizar evaluaciones clínicas y la aprobación de que el operador de alimento era común para las parvadas A1 y B1, y C1 y C2, se decidió investigar el alimento. Nuestros hallazgos revelaron que el alimento contenía niveles de nicarbazina y narasina de hasta cinco y 14 veces, respectivamente, por encima de los límites máximos permitidos por la Unión Europea para especies no objetivo. Por otro lado, no se observaron anomalías significativas en los niveles de vitaminas, lo que también se describió como la etiología de las anomalías observadas. El cambio a un alimento no contaminado provocó que los signos clínicos y los parámetros de producción regresaran a los rangos esperados. Este informe enfatiza la importancia de considerar la contaminación del alimento por nicarbazina y narasina como una causa potencial de pérdidas en la eclosión de especies no objetivo, incluso en ausencia de otros signos clínicos.

Safety and efficacy of a feed additive consisting of narasin (Monteban® G100) for chickens for fattening (Elanco GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the coccidiostat narasin (Monteban® G100) for chickens for fattening. In a previous opinion, uncertainties remained on the identification and characterisation of the non-genetically modified production strain of the active substance narasin. The Panel could not conclude either on the safety of Monteban® G100 for chickens for fattening or on the efficacy of the additive at the minimum applied concentration. The FEEDAP Panel excluded risks for environment but the risk for sediment compartment could not be assessed. The applicant provided supplementary information to cover the data gaps and substituted the narasin production strain from Streptomyces spp. NRRL 8092 to Streptomyces spp. NRRL B-67771. The information submitted to taxonomically identify the production strain did not allow to assign it to any described microbial species. Based on the information provided, the Panel concluded that the use of Monteban® G100 did not raise safety concerns as regards the production strain for the target animal, consumer, user and environment. The Panel concluded that 70 mg narasin/kg complete feed was safe for chickens for fattening with a margin of safety of 1.4; narasin from Monteban® G100 was unlikely to increase shedding of Salmonella Enteritidis, Salmonella Typhimurium and Campylobacter jejuni. Narasin, when used in chickens for fattening at 70 mg/kg feed, was not expected to pose a risk to the aquatic compartment and to sediment, while a risk for the terrestrial compartment could not be excluded. No risk for groundwater was expected, nor for secondary poisoning via the terrestrial food chain, but the risk of secondary poisoning via the aquatic food chain could not be excluded. The Panel concluded that 60 mg narasin/kg feed was efficacious in controlling coccidiosis in chickens for fattening.

Oxidative stress induction by narasin augments doxorubicin's efficacy in osteosarcoma.

Complications and fata toxicity induced by chemotherapy are the main challenge for clinical management of osteosarcoma. The identification of agents that can augment the efficacy of chemotherapy at lower doses may represent an alternative therapeutic strategy. Narasin is a polyether antibiotic widely used in veterinary medicine. In this study, we show that narasin is active against osteosarcoma cells at the same concentrations that are less toxic to normal cells. This effect is achieved by growth inhibition and apoptosis induction, which is mediated by oxidative stress and damage, and mitochondrial dysfunction. The antioxidant N-acetyl-l-cysteine (NAC) abolishes the anti-osteosarcoma activity. Importantly, narasin significantly augments doxorubicin's efficacy in both osteosarcoma cell culturing system and subcutaneous implantation mouse model. The combination of narasin and doxorubicin at non-toxic doses completely arrests osteosarcoma growth in mice. Our results suggest that the concurrent administration of doxorubicin and narasin could present a viable alternative therapeutic approach for osteosarcoma.

Study of the effect of administration of narasin or antibiotics on in vivo selection of a narasin- and multidrug-resistant Enterococcus cecorum strain.

Enterococcus cecorum is a member of the normal poultry gut microbiota and an emerging poultry pathogen. Some strains are resistant to key antibiotics and coccidiostats. We evaluated the impact on chicken excretion and persistence of a multidrug-resistant E. cecorum of administering narasin or antibiotics. E. cecorum CIRMBP-1294 (Ec1294) is non-wild-type to many antimicrobials, including narasin, levofloxacin, oxytetracycline and glycopeptides, it has a low susceptibility to amoxicillin, and carries a chromosomal vanA operon. Six groups of 15 chicks each were orally inoculated with Ec1294 and two groups were left untreated. Amoxicillin, oxytetracycline or narasin were administered orally to one group each, either at the recommended dose for five days (amoxicillin, oxytetracycline) or continuously (narasin). Faecal samples were collected weekly and caecal samples were obtained from sacrificed birds on day 28. Ec1294 titres were evaluated by culture on vancomycin- and levofloxacin-supplemented media in 5 % CO2. For inoculated birds given narasin, oxytetracycline or no antimicrobials, vancomycin-resistant enterococci were searched by culture on vancomycin-supplemented media incubated in air, and a PCR was used to detect the vanA gene. Ec1294 persisted in inoculated chicks up to day 28. Compared to the control group, the Ec1294 titre was significantly lower in the amoxicillin- and narasin-receiving groups on days 21 and 28, but was unexpectedly higher in the oxytetracycline-receiving group before and after oxytetracycline administration, preventing a conclusion for this group. No transfer of the vanA gene to other enterococci was detected. Other trials in various experimental conditions should now be conducted to confirm this apparent absence of co-selection of the multi-drug-resistant E. cecorum by narasin or amoxicillin administration.

Effects of supplementing narasin to Bos indicus heifers during late-gestation and lactation on development of the offspring.

This experiment evaluated the effects of supplementing narasin during late-gestation and lactation on productive and physiological responses of Bos indicus beef heifers and their offspring. Pregnant, nulliparous Nelore heifers (N = 88) that conceived under the same fixed-time artificial insemination protocol and to the same sire were used. Heifers were ranked by maternal ability genomic score, body weight (BW) and body condition score (BCS) and allocated to 44 drylot pens (2 heifers per pen; 10 × 25 m). Pens were ranked by these traits and alternatively assigned to receive (NAR) or not (CON) 0.260 mg of narasin/kg of heifer BW daily (Elanco Saúde Animal, São Paulo, Brazil). Narasin was mixed into a supplement offered at 0.30% of heifer BW from day 0 until heifers weaned their calves (day 316), whereas CON heifers received the same supplement without narasin addition. Heifers received Urochloa brizantha hay and water for ad libitum consumption (days 0 to 316) and calved between days 97 to 112 of the experiment. After calving, heifers and offspring had access to hay and supplement; hence, supplements and narasin were offered according to heifer + calf BW beginning on day 162. No treatment differences were detected (P ≥ 0.18) for heifer BW and BCS during the experiment, although BW loss from day 0 to calving was less (P = 0.04) in NAR compared to CON heifers. Hay intake during the experiment did not differ (P = 0.79) between treatments. Serum IGF-I concentrations were greater (P = 0.05) for NAR heifers on day 60 of the experiment and did not differ (P ≥ 0.28) between treatments 24 h and 30 d after calving (treatment × day interaction; P = 0.04). No treatment effects were detected (P ≥ 0.58) for calf birth BW. Serum concentrations of total protein 24 h after birth were greater (P = 0.04) in calves from NAR compared with CON heifers, and a tendency (P = 0.10) for a similar outcome was noted for serum IgG concentrations. Diarrhea incidence did not differ (P = 0.16) between treatments, although the number of total diarrhea cases per calf were greater (P = 0.03) in the CON offspring. Growth rate of calves from NAR heifers tended (P = 0.08) to be greater, resulting in heavier calves at weaning (P ≤ 0.04) compared with CON offspring. Collectively, these outcomes indicate narasin supplementation to beef heifers as a nutritional alternative to improve cow-calf productivity via developmental programming effects during gestation, as well as direct consumption by their nursing offspring.

Research note: effects of different anticoccidial regimens on the growth performance, hematological parameters, immune response, and intestinal coccidial lesion scores of yellow-feathered broilers.

Yellow-feathered broiler chickens generally have a longer growth cycle than white broilers and therefore face different coccidiosis challenges. General single vaccine and drug regimens struggle to prevent coccidiosis for yellow broilers. In this study, a single vaccine, and a combination of coccidiostat regimens was employed to explore the preventative and control effects of different pilot regimens on coccidiosis in yellow-feathered broilers. A total of 2,000 one day old Chinese Huang Youma female broilers were allocated into 4 experimental groups, each with 5 replicates. All birds were fed the same starter feed from Days 1 to 25, and all groups were inoculated with a vaccine on Day 4. After Day 26, the groups were then fed as follows: (1) Negative control group: basal diet + vaccine (NC); (2) NC + maduramycin (NCMD); (3) NC + narasin (NCNR); and (4) NC + salinomycin (NCSL). From Days 26 to 75, the NCNR group had a lower FCR than the other groups. The 75-d BW was higher in the NCNR group than in the NCSL group but was not significantly higher than that in the NC and NCMD groups. The growth performance followed the same trend during the whole experiment (Days 1-75). Compared to the NC group, the NCNR and NCSL groups had higher intestinal mucosa SIgA concentrations at Day 40 and Day 60 (P < 0.001); however the NCMD group had lower IgG levels at Day 40 and Day 60 (P = 0.036, P = 0.006 respectively). The combination groups had significantly reduced AKP levels and urine acid concentrations at Day 60 in comparison to those of the NC group (P = 0.004). The NCNR and NCMD groups had less severe intestinal coccidiosis lesion scores than the NC and NCSL groups in older birds. Thus, a single vaccine and/or combinations with different coccidiostats had different effects on broilers. The NCNR group showed comparatively better growth performance, blood biochemical indices, immune response, and coccidiosis lesion scores.

Effects of narasin supplementation frequency on intake, ruminal fermentation parameters, and nutrient digestibility of Bos indicus Nellore steers fed with forage-based diets.

The study aimed to evaluate if the frequency of narasin supplementation impacts dry matter intake, ruminal fermentation parameters, and apparent digestibility of nutrient in Nellore (Bos indicus) steers fed forage-based diets. A total of 32 rumen-cannulated Nellore steers (initial body weight [BW] = 317 ± 27 kg; age =18 ± 1 mo) were assigned to individual pens in a randomized complete block design according to their initial shrunk BW. Within block, steers were randomly assigned to 1 of 4 treatments: 1) forage-based diet without the addition of narasin (CON; n = 8), 2) CON diet plus 13 ppm of narasin every 24 h (N24; n = 8), 3) CON diet plus 26 ppm of narasin every 48 hours (N48; n = 8), or 4) CON diet plus 39 ppm of narasin every 72 hours (N72; n = 8). The experimental period lasted 30 d, with 18 d for diet adaptation and 12 d for sample collection. The experimental diets contained 95% of Tifton-85 (Cynodon dactylon spp.) haylage and 5% ground corn used as a delivery vehicle for narasin. Ruminal fluid was obtained from d 25 to 30 at 6 h after feeding to determine ruminal fermentation parameters. Narasin supplementation frequency did not affect (P ≥ 0.22) nutrient intake and total tract apparent digestibility. Steers fed N24 and N48 had reduced (P = 0.02) ruminal acetate concentration compared with CON and N72. Daily supply of narasin increased (P = 0.01) the molar proportion of propionate compared with CON and N72, and it did not differ between N24 vs. N48, N48 vs. N72, and N72 vs. CON. Also, N48 steers had greater (P = 0.01) rumen propionate concentration compared with CON. The N24 treatment decreased the Ac:Prop (P = 0.01) and AcBut:Prop (P = 0.02) ratio compared with CON and N72, while N48 had reduced (P = 0.01) Ac:Prop and AcBut:Prop ratio when compared with CON steers. Steers fed N24 and N48 had greater (P = 0.04) ruminal short-chain fatty acids compared with CON, but it did not differ (P > 0.11) between N24, N48, and N72. Supplementing narasin to steers fed forage-based diets decreased (P < 0.01) ruminal ammonia concentration compared with CON steers regardless of supplementation frequency, being the least result observed for N24 steers. Collectively, narasin supplementation frequency affected fermentation parameters without altering the nutrient intake and total tract apparent digestibility. Hence, decreasing frequency of narasin supplementation to Nellore steers fed a forage-based diet did not reduce the capacity to modulate rumen fermentation parameters.

Effects of narasin or virginiamycin on growth performance and carcass characteristics of growing and finishing pigs.

The objective of this experiment was to determine the effects of narasin (NAR; Skycis®; Elanco Animal Health, Greenfield, IN) or virginiamycin (VIR; Stafac®; Phibro Animal Health Corporation, Teaneck, NJ) on finishing pig growth performance and carcass characteristics. Two separate experiments were conducted at the same site in 2013 and 2014. A total of 576 pigs (initial BW = 23.2 ± 0.19 kg) were housed in 24 pens with 8 pigs per pen in Exp. 1. In Exp. 2, a total of 888 pigs (initial BW = 26.2 ± 0.12 kg) were housed in 39 pens with 8 pigs per pen. Treatments consisted of a series of unmedicated corn-soybean meal diets (CON), CON + NAR (15 mg/kg), or CON + VIR (11 mg/kg) fed for 108 d (Exp. 1) or 109 d (Exp. 2). Pen was the experimental unit in both studies. Data were analyzed as a randomized complete block design with the main effects of block and treatment (Exp. 1) and as an incomplete block design with the fixed effect of treatment and the random effects of barn and barn within block (Exp. 2). In Exp.1, NAR and VIR increased (P < 0.05) ADG and ADFI from days 0 to 28, and BW on days 28, 56, 76, and 97 as compared to pigs fed CON. During days 0-28, pigs fed NAR had a greater (P < 0.05) G:F than those fed CON or VIR. Also, during days 28-56 pigs fed VIR had a greater (P < 0.05) ADFI than pigs fed CON. Pigs fed NAR or VIR had greater (P < 0.05) carcass yield than those fed CON. In Exp.2, feeding NAR increased (P < 0.05) pig BW from days 54 through 96 compared to pigs fed CON or VIR. No differences (P > 0.05) in ADG were detected between pigs fed VIR and CON through the first 74 day, but ADG of pigs fed VIR was similar to (P > 0.05) those fed NAR from days 26 to 54. From day 0 to 109, NAR improved ADG compared to pigs fed VIR, which also had similar gain to those consuming CON (P = 0.04). Feed efficiency was similar between pigs fed NAR and VIR with pigs fed CON intermediate (P = 0.05). Pigs fed NAR had a greater (P < 0.05) HCW and loin depth than those fed CON or VIR. A subtherapeutic dose of VIR showed improvements in growth performance that were similar to NAR in one experiment. Although there were differences in the magnitude of growth and carcass effects of NAR between the two studies, pigs fed NAR showed at least a tendency to have greater G:F and in some cases increased carcass weight and yield compared to pigs consuming nonmedicated feed.

Effects of rearing system and narasin on growth performance, gastrointestinal development, and gut microbiota of broilers.

This study was conducted to evaluate the effects of 3 rearing systems (FL: flooring litter rearing, MC: multilayer cage rearing, PN: plastic net rearing) with or without supplemental narasin on growth performance, gastrointestine development and health of broilers. A total of 2,400 one-day-old Ross 308 mixed-sex broilers (1:1 ratio of males and females) were used in a completely randomized design utilizing a 3 × 2 factorial arrangement of treatments, with 12 replicates per treatment. Each replicate for FL, MC, and PN consisted of 34 birds per floor pen, 30 birds per cage, and 36 birds per net pen, respectively, ensuring the same stocking density (12 birds/m2) across the 3 systems. Results showed that lower ADG (average daily gain), ADFI (average daily feed intake), and FCR (feed conversation ratio) observed in the MC group than those of the other 2 systems from 1 to 36 d of age (P < 0.05). Narasin inclusion in the diets decreased ADFI and FCR significantly (P < 0.05). Multilayer cage and PN rearing systems reduced the relative weight of the gizzard significantly (P < 0.05). Compared with FL, MC reduced the relative weight of the duodenum, jejunum, and ileum (P < 0.05). The mRNA expression levels of the ileal IL-1ß and IFN-γ in FL were higher than those in PN and MC (P < 0.05). Narasin decreased the ileal mRNA expression of TNF-α (P < 0.05). Different rearing systems changed the ileal microflora structure of broilers. The FL system increased the ileal microbial diversity of broilers and the relative abundance of Actinobacteria. Narasin combined with MC increased the relative abundance of Proteobacteria. In conclusion, birds reared in PN had a higher body weight. The MC birds had poorer intestinal development and health condition, higher abundance of Proteobacteria, but better FCR. The FL rearing appeared to be propitious for gastrointestinal development and health. Narasin inclusion in the diets improved FCR and changed the relative abundance Proteobacteria of broilers.

Effects of narasin supplementation on dry matter intake and rumen fermentation characteristics of Bos indicus steers fed a high-forage diet.

This study evaluated the effects of narasin on intake and rumen fermentation characteristics of Bos indicus steers offered a high-forage diet for 140 d. On day 0 of the study, 30 rumen-fistulated Nellore steers [initial body weight (BW) = 281 ± 21 kg] were assigned to 30 individual pens in a randomized complete block design according to their initial BW. Animals were randomly assigned to 1 of the 3 treatments: 1) forage-based diet without narasin (CONT; n = 10), 2) CONT diet plus 13 ppm of narasin (13NAR; n = 10), and 3) CONT diet plus 20 ppm of narasin (20NAR; n = 10). The forage used was Tifton-85 (Cynodon dactylon spp.), whereas the carrier for narasin was a 50:50 mixture of soybean hull:corn. The experimental period was divided into 5 periods of 28 d each. Throughout the experimental period, total dry matter intake (DMI) was recorded daily, whereas mineral salt intake was recorded weekly. Blood and ruminal fluid samples were collected on day 0 (prior to treatment feeding), 28, 56, 84, 112, and 140 of the study. Moreover, total tract apparent nutrient digestibility was performed for a 5-d period every 28 d. No treatment effects were observed on forage, mineral, concentrate, or total DMI (P ≥ 0.22). Nonetheless, 13NAR tended to have a greater mineral intake vs. 20NAR cohorts (P = 0.08) Narasin-supplemented animals had reduced rumen acetate, Ac:Pr ratio, as well as greater (P ≤ 0.02) rumen propionate concentrations vs. CONT cohorts. Moreover, 13NAR increased rumen propionate and decreased butyrate, Ac:Pr vs. 20NAR cohorts (P ≤ 0.01). Throughout the experimental period, narasin-supplemented animals had reduced ammonia concentrations vs. CONT cohorts (P < 0.01), whereas no differences were observed between 13NAR and 20NAR (P = 0.80). No treatment or dose effects were observed (P ≥ 0.23) on DM, organic matter (OM), protein, neutral detergent fiber (NDF), acid detergent fiber (ADF), and mineral digestibility. Animals fed 13NAR had a reduced mean plasma urea concentration vs. CONT cohorts (P = 0.03), whereas no further differences were observed (P ≥ 0.12). In summary, narasin supplementation to beef steers offered a high-forage diet did not impact forage, mineral, and total DMI, as well as nutrient digestibility, whereas rumen fermentation characteristics, rumen ammonia, and plasma urea concentrations were positively impacted and lasted throughout the experimental period. Additionally, 13 ppm of narasin resulted in a reduced Ac:Pr ratio and rumen ammonia when compared to animals supplemented with 20 ppm.

NarAB Is an ABC-Type Transporter That Confers Resistance to the Polyether Ionophores Narasin, Salinomycin, and Maduramicin, but Not Monensin.

Polyether ionophores are antimicrobial compounds used as feed additives in poultry feed to control diseases caused by coccidia. In addition to the anticoccidial activity of these compounds, polyether ionophores also contain antibacterial properties. Resistance to the polyether ionophore narasin was recently shown to exist on mobile plasmids in Enterococcus faecium and the resistance mechanism was suggested to be associated with a two-gene operon encoding an ABC-type transporter. In this study we demonstrate that the genes encoding the putative narasin resistance mechanism confers reduced susceptibility to the polyether ionophores narasin, salinomycin and maduramicin, but not to monensin and suggest that this resistance mechanism should be referred to as NarAB. Importantly, NarAB does not affect the susceptibility of E. faecium to any of the tested antimicrobial compounds that are used in clinical medicine. However, we show that conjugation in the presence of certain polyether ionophores increases the number of vancomycin resistant E. faecium suggesting that narasin and certain other polyether ionophores can contribute to the persistence of VRE in poultry populations.

The rise and fall of a vancomycin-resistant clone of Enterococcus faecium among broilers in Sweden.

OBJECTIVES: Historically, vancomycin-resistant enterococci (VRE) have been very common among farm animals in Europe, and they can still be readily isolated using media supplemented with vancomycin. An increase in the occurrence of VRE among broilers in Sweden was reported during 2000-2005. This was due to the spread of one clone of VRE in the apparent absence of selective pressure. The aims of this study were to estimate the current occurrence of VRE among Swedish broilers and to investigate if there had been any changes with regards to the dominating clone and antimicrobial resistance pattern. METHODS: Caecal samples (n=100) collected at slaughter from healthy broilers were cultured on Slanetz-Bartley agar supplemented with vancomycin (16 mg/L). Presumptive VRE were identified to species using MALDI-TOF MS, susceptibility tested using broth micro-dilution, and whole genome sequenced to investigate the genetic relationship with previous isolates. RESULTS: Eleven (11%) of the samples were positive for VRE. This was a statistically significant decrease in the proportion of positive samples from 2010. The same clone as before still prevailed. CONCLUSIONS: The occurrence of VRE among broilers in Sweden has decreased. However, just as the occurrence of VRE among Swedish broilers increased in the apparent absence of selective pressure, the reasons for the decrease is unknown.

Modification of the terms of authorisation regarding the maximum inclusion level of Maxiban® G160 (narasin and nicarbazin) for chickens for fattening.

Following the request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the proposed modification of the terms of the authorisation regarding the maximum inclusion level of Maxiban® G160. The FEEDAP Panel cannot conclude on the safety of Maxiban® G160 at a dose level of 70 + 70 mg/kg feed for the target species. The use of Maxiban® G160 in diets for chickens for fattening at the maximum proposed dose complies with the maximum residue levels (MRLs) in force of narasin and 4,4'-dinitrocarbanilide (DNC) at 0-day withdrawal except for DNC in kidney which was slightly above the MRL. Compliance with DNC MRLs was seen in all tissues at 1-day withdrawal. Based on the available data, the FEEDAP Panel cannot conclude on the safety of Maxiban® G160 for the environment due to the risk identified for the terrestrial organisms due to DNC. Moreover, the high persistence and hydrophobicity of DNC indicate that there might be a risk for bioaccumulation but the risk for secondary poisoning was not identified. The potential of DNC to accumulate in soil over the years should be investigated by monitoring in a field study. The FEEDAP Panel would not be in the position to conclude on the efficacy of Maxiban® G160 in chickens for fattening based on the data provided for the dose of 40 + 40 mg narasin + nicarbazin/kg feed.

Effects of supplement type and narasin inclusion on supplement intake by Bos indicus beef bulls grazing a warm-season forage.

This study aimed to evaluate the effects of supplement type and narasin inclusion on the frequency and supplement intake of grazing Bos indicus beef bulls. Four hundred animals were ranked by initial BW (383 ± 35 kg) and allocated into one of four paddocks of Brachiaria brizantha cv. Marandú (100 animals/paddock). Paddocks were randomly assigned to receive either a mineral salt (MIN) or a protein-energetic supplement (PREN) containing or not narasin (N) for a 90-d period. An individual electronic data capture system with 11 feed bunks was used to individually measure supplement intake and meal frequency in each paddock. The evaluations and analysis of individual intake, frequency of visits to the feeder, and intake per visit (I/V) were performed every 15 d and classified as periods (PR1 through PR6). All data were analyzed as a 2 × 2 factorial design with the PROC MIXED procedure of SAS. A supplement type × N × PR interaction was observed (P < 0.0001) for daily supplement intake. No differences were observed between MIN, whereas PREN had a greater (P ≤ 0.03) supplement intake on PR1 and PR3, but a reduced supplement intake on PR6 compared with PREN + N (P = 0.02). Moreover, no supplement type × N interaction (P = 0.47) or N (P = 0.44) effects were observed for daily supplement intake in the present study. A supplement type × N × PR interaction was detected (P < 0.0001) for the frequency of visits in the feeders. Throughout the experimental period, animals from the MIN + N had a greater (P ≤ 0.02) frequency of visits compared with MIN cohorts. A supplement effect was detected for I/V (P = 0.02), whereas neither a narasin effect (P = 0.74) nor interactions (P ≥ 0.16) were observed. Animals offered PREN had a greater I/V when compared with MIN cohorts (145 vs. 846 g/d for MIN and PREN, respectively; SEM = 16.1). When these data are reported as percentage of days visiting the feeder within each PR, MIN and MIN + N animals visited the feeder for 25.8% and 35.9% of the days, respectively. Conversely, no differences were observed (P = 0.65) in the overall mean visits per PR between PREN and PREN + N (12.8 vs. 12.3 d for PREN and PREN + N, respectively; SEM = 0.195). As percentage of days visiting the feeder, PREN and PREN + N visited the feeder for 85.1% and 81.9% of the days, respectively. In summary, narasin inclusion did not reduce supplement intake, regardless of supplement type, but increased the frequency of visits to the feeder for the MIN treatment.

Impact of coccidiostat and phytase supplementation on gut microbiota composition and phytate degradation in broiler chickens.

BACKGROUND: There is good evidence for a substantial endogenous phytase activity originating from the epithelial tissue or the microbiota resident in the digestive tract of broiler chickens. However, ionophore coccidiostats, which are frequently used as feed additives in broiler diets to prevent coccidiosis, might affect the bacterial composition and the abundance of phytase producers in the gastrointestinal tract. The aim of the present study was to investigate whether supplementation of a frequently used mixture of the coccidiostats Narasin and Nicarbazin alone or together with a phytase affects microbiota composition of the digestive tract of broiler chickens, characteristics of phytate breakdown in crop and terminal ileum, and precaecal phosphorus and crude protein digestibility. RESULTS: Large differences in the microbial composition and diversity were detected between the treatments with and without coccidiostat supplementation. Disappearance of myo-inositol 1,2,3,4,5,6-hexakis(dihydrogen phosphate) (InsP6) in the digestive tract, precaecal P digestibility, inorganic P in blood serum, and the concentration of inositol phosphate isomers in the crop and ileum digesta were significantly affected by phytase supplementation, but not by coccidiostat supplementation. Crude protein digestibility was increased by coccidiostat supplementation when more phosphate was available. Neither microbial abundance and diversity nor any other trait measured at the end of the experiment was affected by coccidiostat when it was only supplemented from day 1 to 10 of age. CONCLUSIONS: The coccidiostats used herein had large effects on overall microbiota composition of the digestive tract. The coccidiostats did not seem to affect endogenous or exogenous phytase activity up to the terminal ileum of broiler chickens. The effects of phytase on growth, phosphorus digestibility, and myo-inositol release were not altered by the presence of the coccidiostats. The effects of phytase and coccidiostats on nutrient digestibility can be of significant relevance for phosphorus and protein-reduced feeding concepts if confirmed in further experiments.

Safety and efficacy of Monteban® G100 (narasin) for chickens for fattening.

The feed additive Monteban® G100, containing the active substance narasin, an ionophore anticoccidial, is intended to control coccidiosis in chickens for fattening at a dose of 60-70 mg/kg complete feed. Narasin is produced by fermentation. Limited data on the taxonomic identification of the production strain did not allow the proper identification of strain NRRL 8092 as Streptomyces aureofaciens. The FEEDAP Panel cannot conclude on the absence of genetic determinants for antimicrobial resistance in Streptomyces spp. under assessment. Based on the available data set, the FEEDAP Panel cannot conclude on the safety of Monteban® G100 for chickens for fattening. The simultaneous use of Monteban® G100 and certain antibiotic drugs (e.g. tiamulin) is contraindicated. Narasin is not genotoxic. No indication of carcinogenicity or developmental toxicity was found at the doses tested in the mouse, rat and rabbit. The lowest no observed effect level (NOEL) identified in the oral toxicity studies was 0.5 mg/kg body weight (bw) per day for the neuropathy seen in a one-year dog study. The acceptable daily intake (ADI) derived from this NOEL is 0.005 mg narasin/kg bw applying a uncertainty factor of 100. Monteban® G100 is safe for the consumer. Maximum residue limits (MRLs) of 50 µg narasin/kg for all wet tissues ensure consumer safety. Monteban® G100 is irritatant to the eyes but not to the skin. It has the potential to induce skin sensitisation. Inhalation exposure would pose a risk to persons handling the additive. Narasin, when used as a feed additive for chickens for fattening at 70 mg/kg feed, is not expected to pose a risk to the environment. The risk for sediment compartment cannot be assessed. The FEEDAP Panel cannot conclude on the efficacy of Monteban® at the minimum applied dose of 60 mg narasin/kg complete feed for chickens for fattening.

Safety and efficacy of Monteban® G100 (narasin) for ducks for fattening.

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Monteban® G100 for ducks. Monteban® G100, containing narasin, is intended for the prevention of coccidiosis in ducks for fattening at a dose range of 60-70 mg/kg of complete feed. Narasin from Monteban® G100 is safe for ducks for fattening at a level of 70 mg/kg complete feed with a margin of safety of about 4. The FEEDAP Panel assumes that the residues in duck tissues would be of the same magnitude as those measured in the physiologically similar major species, chickens for fattening. The use of Monteban® G100 at a maximum concentration of 70 mg/kg complete feed for ducks for fattening is safe for the consumer without applying a withdrawal period, provided the maximum residue limit (MRL) of 50 µg narasin/kg for all wet tissues would not be exceeded. Monteban® G100 is irritant to the eyes but not to the skin. It has the potential to induce skin sensitisation. The acute systemic toxicity following dermal application is low. Inhalation exposure would pose a risk to persons handling the additive. Narasin, when used as feed additive for ducks for fattening at 70 mg/kg feed, is not expected to pose a risk to the environment. The risk for sediment compartment cannot be assessed. Narasin is not considered to have a bioaccumulation potential. Insufficient data were provided to allow a conclusion on the efficacy of Monteban® G100 in ducks.