Metaphylactic Use Research Articles

Determining the Economically Optimum Metaphylactic Strategy for Cattle Cohorts of Varied Demographic Characteristics.

Metaphylactic antibiotic use in feeder cattle is a common practice to control respiratory disease. Antimicrobial stewardship is important to ensure continued efficacy and to protect animal welfare. The objective of this study is to identify characteristics of cohorts of cattle that had not received metaphylaxis that would have benefited economically from the use of metaphylaxis. Cohorts (n = 12,785; 2,206,338 head) from 13 feedlots that did not receive metaphylaxis were modeled using an economic model to estimate net returns for three metaphylactic options. Logistic regression models with covariates for entry weight, sex, average daily weight gain, number of animals per cohort, and days on feed, with feedlot as a random effect, were used to determine the model-adjusted probability of cohorts benefiting economically from metaphylaxis. Most (72%) cohorts in this data set that had not received metaphylaxis at arrival would not economically benefit from metaphylaxis. Sex, entry weight category, number of cattle in the cohort, and average daily weight gain were associated with the likelihood of benefitting economically from metaphylaxis. The results illustrated that cattle cohort demographics influenced the probability that cohorts would benefit economically from metaphylaxis and the type of metaphylaxis utilized, and integrating this information has the potential to influence the metaphylaxis decision.

PSV-8 Development of genetically engineered microbes as probiotics to enhance ruminant productivity

Abstract Alternatives to antibiotics (especially metaphylactic use of antibiotics in livestock) are critically needed to ensure animal and human health while meeting the increasing food demand of the growing human population. One of the proposed alternatives to antibiotic use that is gaining momentum is the use of probiotics or direct-fed microbials (DFMs), which are live microbes that have specialized functions that improve gastrointestinal health and performance. However, to date, most probiotics or DFMs tested as alternative to antibiotics to reduce pathogen colonization have shown limited effectiveness with inconsistent results. This is due to the fact that only, generally accepted as safe (GRAS) bacterial strains are being used as DFMs or probiotics in the animal industry. However, metagenome studies have clearly shown the presence of unique biosynthetic gene clusters and other beneficial genes within gut environments in livestock species in non-GRAS organisms. As such, with advances in gene editing techniques, tools are now available to strategically integrate beneficial genes found in non-GRAS approved microbial strains into GRAS approved strains to develop genetically engineered microbes with beneficial functions. As a first step towards developing genetically engineered microbes to improve animal health and performance, we engineered a biosynthetic gene cassette identified from rumen microbes into GRAS approved Bacillus strains. We utilized chasis-independent recombinase-assisted genome engineering (CRAGE) and random transposon mutagenesis to insert biosynthetic genes into GRAS approved strains. Furthermore, we performed functional screening experiments to identify strains containing the engineered gene cassette and confirmed using sequencing. This approach can be used to engineer beneficial genes and generate personalized probiotics to improve animal health and productivity.

Ligilactobacillus salivarius MP100 as an Alternative to Metaphylactic Antimicrobials in Swine: The Impact on Production Parameters and Meat Composition.

The metaphylactic use of antimicrobials in swine farms contributes to the emergence of antibiotic-resistant bacteria, which constitutes a major challenge for public health. Alternative strategies are required to eradicate their routine use. In a previous study, metaphylactic antimicrobials were replaced by the administration of Ligilactobacillus salivarius MP100 to sows and piglets for two years. This practice positively modified the fecal microbiota and metabolic profiles in the farm. In this work, the farm dataset was used to compare the productivity-related parameters between a 2-year period of routine metaphylactic antibiotherapy and the first 2 years of a replacement with the probiotic strain. The probiotic period improved these productivity-related parameters, from litter size to growth performance. In addition, samples of Longissimus lumborum, including skin and subcutaneous fat, were obtained from the animals ingesting the probiotic strain and controls (metaphylactic antibiotherapy) and analyzed for their pH, water holding capacity, composition, and metabolic profiling. The probiotic intake did not negatively affect the meat composition and was associated with an increase in inosine concentration and a slight tendency for increasing the intramuscular fat content. These factors are considered as biomarkers of meat quality. In conclusion, the substitution of metaphylactic antimicrobials with the administration of the probiotic strain was associated with beneficial productivity and meat quality outcomes.

The effects of administering different metaphylactic antimicrobials on growth performance and health outcomes of high-risk, newly received feedlot steers.

Bovine respiratory disease (BRD) is the primary animal health concern facing feedlot producers. Many antimicrobial mitigation strategies are available, but few studies have compared feedlot performance during both the receiving and finishing periods following application of different antimicrobials used as metaphylaxis at arrival. The objective of this study was to compare antimicrobial metaphylaxis methods on clinical health and growth performance across both the receiving and finishing periods. A total of 238 multiple-sourced steers in two source blocks were used in a generalized complete block design. The four treatments included: 1) a negative control, 5 mL of sterile saline injected subcutaneously (CON); 2) subcutaneous administration of florfenicol at 40 mg/kg of BW (NUF); 3) subcutaneous administration of ceftiofur in the posterior aspect of the ear at 6.6 mg/kg of BW (EXC); and 4) subcutaneous administration of tulathromycin at 2.5 mg/kg of BW (DRA). The morbidity rate for the first treatment of BRD was decreased for the DRA and EXC treatments compared to CON and NUF (P < 0.01). Additionally, average daily gain (ADG), dry matter intake (DMI), and gain-to-feed (G:F) were greater (P ≤ 0.02) in the DRA treatment during the receiving period compared to all other treatments. The ADG was also greater (P < 0.05) for EXC than the CON treatment throughout the finishing period. Nonetheless, other growth performance variables did not differ among metaphylactic treatments during the finishing period (P ≥ 0.14). Likewise, no differences in carcass characteristics or liver abscess score were observed (P ≥ 0.18). All complete blood count (CBC) variables were affected by day (P ≤ 0.01) except mean corpuscular hemoglobin concentration (P = 0.29). Treatment × time interactions were observed for platelet count, white blood cell (WBC) count, monocyte count and percentage, and lymphocyte percentage (P ≤ 0.03). However, there were no observed hematological variables that differed among treatment (P ≥ 0.10). The results indicate that some commercially available antimicrobials labeled for metaphylactic use are more efficacious than others in decreasing morbidity rate.

Cross-Sectional Survey of Prophylactic and Metaphylactic Antimicrobial Use in Layer Poultry Farming in Cameroon: A Quantitative Pilot Study.

An evaluation of the patterns of antimicrobial use in livestock can help understand the increasing level of antimicrobial resistance worldwide. This study aimed at evaluating antimicrobial usage in modern layer poultry farms in the West Region of Cameroon. In this light, 70 layer poultry farms and 4 veterinary pharmacies were surveyed. Data on antimicrobial use were collected through interviews using a quantitative-frequency questionnaire and consultation of medical records. The four veterinary pharmacies sold a total of 2.8 tons of antimicrobials (active ingredients) during 2011. At the level of farms, 297 kg of antimicrobials (active ingredients) were used in the 50 layer poultry farms surveyed. Tetracycline, sulfonamides, quinolones, and β-lactams (aminopenicillins) were the most sold and used drugs in layer farms. As for treatment indication, metaphylactic (58.1%) and prophylactic (41.9%) treatments were the most observed practices, and nearly all (99%) treatments were administered per os as remedies to respiratory (33.4%) and digestive (24.7%) tract symptoms. Overall, 78.2% of antimicrobials sold in pharmacies and 67.3% used in the farms belonged to the class of critically important antimicrobials of the WHO categorization of antimicrobials according to their importance to human medicine. Doxycycline, sulfonamide, ampicillin, and streptomycin, which have been banned for layer poultry in the production of eggs for human consumption, were still used in Cameroon. The treatment incidences based on the used daily dose (TIUDD) and animal daily dose (TIADD) were 11.59 and 10.45, respectively. In regard to dosage correctness based on the UDD/ADD ratio, aminoglycosides (100%), macrolides (90.6%), and tetracyclines (74.5%) were the most underdosed, while trimethoprim sulfonamides (45.8%) and β-lactams (35.7%) were overdosed. This study highlights an irrational antimicrobial usage in layer poultry farms. Regulation of the use of antimicrobials and the education of farmers on adequate antimicrobial use are essential to preserve the effectiveness of drugs in both humans and animals.

Scoping Review on Risk Factors and Methods for the Prevention of Bovine Respiratory Disease Applicable to Cow-Calf Operations.

Simple SummaryBovine respiratory disease (BRD) is common in cattle populations and has been named as one of three diseases where antibiotics are most frequently used in cow–calf operations in California. Antibiotics are typically used to treat or prevent the disease, but recent concerns about antibiotic resistance of pathogens in animals or spreading from animals to people have led to the call for more judicious use of these drugs. The present review summarizes the English scientific literature on articles about risk factors for the disease as well as ways to prevent BRD that are applicable to cow–calf operations. Numerous management and animal factors have been identified as increasing the risk for BRD. Vaccinations, metaphylactic use of antibiotics, and feed supplements are areas of research into the prevention of BRD. Genetics have also been explored to determine the heritability of BRD resistance. While vaccinations and metaphylactic use of antibiotics have been evaluated in multiple systematic reviews and meta-analyses, these types of summaries are missing for commonly studied feed supplements, such as yeast and trace minerals, and the use of nitric oxide releasing substance to prevent BRD. Further, it would be beneficial to summarize the knowledge on management related risk factors in literature reviews.The presented scoping review summarizes the available research evidence and identifies gaps in knowledge for bovine respiratory disease (BRD) prevention. Published literature on BRD from 1990 to April 2021 was searched in online databases, including Medline, CAB s, Scopus, Biosis, and Searchable Proceedings of Animal Conferences. Citations were systematically evaluated in a three-stage approach using commercial software and summarized in a scoping review format. A total of 265 publications were included in this review with herd/farm management (27.9%) as the most prevalent factors studied, followed by metaphylaxis (24.5%), vaccinations (24.1%), diet formulations, and nutritional supplementations (17.7%), animal characteristics (10.2%), and less common interventions and risk factors (6.4%). A high proportion of studies under herd/farm management (73%), metaphylaxis (86%), vaccinations (70%), animal characteristics (78%), and less common interventions and risk factors (59%) showed either significant effects on reducing BRD morbidity or significant differences of BRD between treatments. However, diet and nutritional supplementations reduced BRD only in 30% of research publications. Most studies on BRD were performed in feedlot populations, and more studies in cow–calf populations are needed. We further suggest meta-analyses on the use of yeast and trace mineral supplementation, and nitric oxide-releasing solution for BRD prevention.

Engaging with selective dry cow therapy: understanding the barriers and facilitators perceived by Irish farmers

BackgroundSelective dry cow therapy (SDCT) is widely promoted in dairy farming as a method to reduce antimicrobial usage. New legislation introduced by the European Union will restrict and regulate the prophylactic and metaphylactic use of antibiotics from January 2022. Blanket dry cow therapy continues to be a practice engaged in by many farmers in Ireland and for many of these farmers, moving towards SDCT would require a significant infrastructural, behavioural and/or cultural change on their farm. Existing research has reported the important need to understand farmers’ motivations to initiate any substantial behaviour change. However, it is currently unknown what farmers know, think and believe about SDCT in Ireland. The aim of this study was to use qualitative methods to explore what barriers and facilitators farmers perceived to exist with SDCT and explore if they had chosen to implement SDCT after voluntarily participating in a funded dry cow consult with a trained veterinarian, with the objective of maximising the dry period udder health performance and moving safely to SDCT.ResultsIn this study, 19 farmers were contacted, and telephone interviews were conducted regarding farmers’ beliefs about the consequences of SDCT. Audio recordings were professionally transcribed verbatim and analysed qualitatively using an inductive thematic analysis. The analysis identified 6 barriers and 6 facilitators to implementing SDCT. A significant fear of increasing mastitis incidence was evident that caused reluctance towards SDCT and reliance on antibiotics. Mixed perceptions on SDCT, infrastructure limitations, a perceived lack of preventive advice as well as peer influence were presented as barriers to SDCT. Farmers can build confidence when a graded approach to SDCT is implemented, which could help overcome the fear of SDCT and reliance on antibiotics. Regulatory pressure, high standards of farm hygiene and use of targeted veterinary consults were found to facilitate SDCT. Education was suggested to motivate farmers in the future uptake of SDCT. Despite cited negative influences, peer influence can be utilised to encourage the farming community.ConclusionsThis study prioritises areas to facilitate the major behaviour change required as a dairy industry in order to move from blanket dry cow therapy to SDCT.

Replacement of Metaphylactic Antimicrobial Therapy by Oral Administration of Ligilactobacillus salivarius MP100 in a Pig Farm.

Antibiotic use in swine production contributes to the emergence and spread of resistant bacteria, which poses a threat on human health. Therefore, alternative approaches must be developed. The objective of this work was the characterization of the probiotic properties of a Ligilactobacillus salivarius strain isolated from sow's milk and its application as an inoculated fermented feed to pregnant sows and piglets. The study was carried in a farm in which metaphylactic use of antimicrobials (including zinc oxide) was eliminated at the time of starting the probiotic intervention, which lasted for 2 years. Feces from 8-week-old piglets were collected before and after the treatment and microbiological and biochemical analyses were performed. The procedure led to an increase in the concentrations of clostridia and lactobacilli-related bacteria. Parallel, an increase in the concentration of butyrate, propionate and acetate was observed and a notable reduction in the presence of antibiotic resistant lactobacilli became apparent. In conclusion, replacement of antimicrobials by a microbiota-friendly approach was feasible and led to positive microbiological and biochemical changes in the enteric environment.

Effect of metaphylactic administration of tildipirosin on the incidence of pneumonia and otitis and on the upper respiratory tract and fecal microbiome of preweaning Holstein calves

The objectives of this study were to evaluate the effect of the metaphylactic use of a semi-synthetic long-acting macrolide (tildipirosin) on the prevention of pneumonia and otitis in preweaning Holstein calves, as well as its effects on the microbiome of their upper respiratory tract (URT) and feces. Newborn healthy Holstein heifers, collectively housed, were randomly allocated to 1 of 2 treatment groups: treatment (TRT; n = 932) or control (CTR; n = 927). Calves in the TRT group received a single subcutaneous injection of 4 mg/kg tildipirosin (Zuprevo, Merck Animal Health) at 7 ± 7 d of life. Calves in the CTR group received no drug injection. All enrolled calves were evaluated from 1 to 63 ± 3 d of life (weaning age) and monitored daily for any adverse health events during this period. Daily physical examination was performed to diagnose pneumonia and otitis, and body weight was measured weekly in all animals. From a randomly selected subset of 217 calves, blood samples for biochemical variables analysis and swabs were collected weekly from the URT and rectum for analysis of the nasal and fecal microbiome, respectively, via next-generation sequencing of the 16S rRNA gene. Total bacterial load was evaluated using quantitative PCR. In addition, another subset of 26 calves was randomly selected and fecal swabs were collected in a more intensive sampling to investigate the short-term effect of tildipirosin administration on the fecal microbiome. We performed general mixed linear models and logistic regression to analyze continuous and binary outcomes, respectively. Tildipirosin metaphylaxis reduced the incidence of otitis (CTR = 47.03%; TRT = 37.55%) and tended to reduce the incidence of pneumonia (CTR = 20.71%; TRT = 17.38%) and the overall mortality risk (CTR = 6.69%; TRT = 4.94%). We observed no significant differences between groups for mortality due to pneumonia (CTR = 0.86%; TRT = 0.97%) or mortality due to otitis (CTR = 2.05%; TRT = 1.39%). Calves in the TRT group had a higher average daily gain than calves in the CTR group. Furthermore, metaphylaxis had no significant effects on the total bacterial load, genus, or phylum analysis of the fecal microbiome from the 2 subset groups. However, for the URT microbiota, we observed a significant decrease in total bacterial load for the TRT group compared to the CTR group 1 week after metaphylactic injection. Tildipirosin metaphylaxis decreased the mean relative abundance of the genera Mannheimia, Moraxella, and Pasteurella but significantly increased the mean relative abundance of Mycoplasma. Although tildipirosin had no positive effect on Mycoplasma, it reduced the mean relative abundance of important pathogenic bacteria in the URT and had positive effects for the control of otitis. The metaphylactic use of tildipirosin can be a suitable strategy for the control of otitis on farms with a high prevalence of this disease.

Factors associated with calf mortality and poor growth of dairy heifer calves in northeast Germany

A cross-sectional study was conducted on fifty German dairy farms to identify risk factors for high mortality and poor growth in calves. Between 2012 and 2014, farm visits took place and a questionnaire on farm management practices was completed by in-person interview. In addition, heart girth measurements of calves around weaning were performed to estimate average daily weight gain. Furthermore, blood and faecel samples of calves were collected and a score addressing calf welfare was determined. The epidemiological associations between risk factors and high mortality and poor growth were estimated using two regression models. The factors significantly associated with high calf mortality (> 5%) were a high rate of calves with failure of passive transfer (> 25%) and the metaphylactic use of halofuginone lactate. A small amount of concentrates consumed around weaning, relocating calves more than twice until weaning and a low incidence risk of milk fever (< 5%) were found to be significantly associated with poor growth (median: 675 grams). Although the fifty farms cannot be considered as a representative sample for North-East Germany, the results indicate that the farm management has a big impact on growth and survival of dairy calves and needs to be addressed more thoroughly when raising the future dairy cow.

Metaphylactic Antibiotic Treatment to Prevent the Transmission of Corynebacterium bovis to Immunocompromised Mouse Offspring.

Current methods for eradicating Corynebacterium bovis, such as depopulation, embryo transfer, and cesarean rederivation followed by cross fostering, are expensive, complex, and time-consuming. We investigated a novel method to produce immunocompromised offspring free of C. bovis from infected NOD. Cg-PrkdcscidIl2rgtm1Wgl/SzJ (NSG) breeding pairs. Adult NSG mice were infected with C. bovis, paired, and randomly assigned to either a no-antibiotic control group (NAB, n = 8) or a group that received amoxicillin-clavulanic acid (0.375 mg/mL) in their drinking water for a mean duration of 7 wk (AB group, n = 7), spanning the time from pairing of breeders to weaning of litters. The AB group also underwent weekly cage changes for 3 wk after pairing to decrease intracage C. bovis contamination, whereas the NAB mice received bi-weekly cage changes. Antibiotics were withdrawn at the time of weaning. All litters (n = 7) in the AB group were culture- and qPCR-negative for C. bovis and remained negative for the duration of the study, whereas all litters in the NAB group (n = 6) remained C. bovis positive. A single adult from each breeding pair was sampled at weaning and at 5 and 10 wk after weaning to confirm the maintenance of (NAB) or to diagnose the reemergence (AB) of C. bovis infection. By the end of the study, C. bovis infection had returned in 3 of the 7 (43%) tested AB adults. Our data suggest that metaphylactic antibiotic use can decrease viable C. bovis organisms from adult breeder mice and protect offspring from infection. However, using antibiotics with frequent cage changing negatively affected breeding performance. Nevertheless, this technique can be used to produce C. bovis-free NSG offspring from infected adults and may be an option for salvaging infected immunocompromised strains of mice that are not easily replaced.

The Effect of Metaphylactic Use of Tildipirosin for the Control of Respiratory Disease in Long-Distance Transported Dairy Calves.

The objective of this study was to evaluate the efficacy of two metaphylactic strategies using tildipirosin for the control of bovine respiratory disease (BRD) in dairy calves transported to a heifer raising facility within their first week of life. A total of 2,100 calves were enrolled in the study. Animals were transported for ~1,715 km, from dairies located in Minnesota to a calf raising facility located in New Mexico, where they were housed in individual hutches until weaning. Three days after arrival, calves were randomly allocated into three groups: (1) META1: single subcutaneous (SQ) injection of tildipirosin (Zuprevo™, Merck Animal Health) at enrollment at 4 mg/kg; (2) META2: SQ injection of tildipirosin at enrollment and 17 days later; (3) CON: untreated controls. The BRD incidence was 11.4, 10.8, and 9.4% for calves enrolled in the CON, META1, and META2, respectively (P = 0.44). Lung lesions diagnosed through ultrasonography was found in 21.0, 21.0, and 21.8% of calves enrolled in CON, META1, and META2, respectively (P = 0.99). Mortality tended to be greater for CON calves in comparison to META2 calves (1.5 vs. 0.6%, P = 0.06), but did not differ between calves enrolled in CON and META1 groups (1.5 vs. 1.2%, P = 0.55). Growth was not affected by metaphylaxis. The average daily gain for calves enrolled in CON, META1, and META2 was 517, 518 and 525 g, respectively (P = 0.25). Blood analysis revealed that some of the markers of inflammation assessed were influenced by metaphylaxis. At 27 days after enrollment, META2 calves had decreased concentrations of haptoglobin, serum amyloid A, and aspartate aminotransferase, compared to CON calves (P < 0.05). Additionally, CON calves had increased concentrations of globulins and lower albumin to globulin ratio than META2 calves at the end of the weaning period (P < 0.05). In conclusion, tildipirosin metaphylaxis did not decrease the incidence of BRD nor did it have an impact on weight gain. However, metaphylaxis with two injections of tildipirosin at enrollment and 17 days later tended to reduce mortality and improved the systemic inflammatory status of calves during the preweaning period.

Chestnut extract but not sodium salicylate decreases the severity of diarrhea and enterotoxigenic Escherichia coli F4 shedding in artificially infected piglets.

The development of alternatives to antibiotics is crucial to limiting the incidence of antimicrobial resistance, especially in prophylactic and metaphylactic use to control post-weaning diarrhea (PWD). Feed additives, including bioactive compounds, could be a promising alternative. This study aimed to test two bioactive compounds, sodium salicylate (SA) and a chestnut extract (CE) containing hydrolysable tannins, on the occurrence of PWD. At weaning, 72 piglets were assigned to four treatments that combined two factors: CE supplementation (with 2% of CE (CE+) or without (CE-)) and SA supplementation (with 35 mg/kg BW of SA (SA+) or without (SA-)). Then, 4 days after weaning, all piglets were infected with a suspension at 108 CFU/ml of enterotoxigenic Escherichia coli (ETEC F4ac). Each piglet had free access to an electrolyte solution containing, or not, SA. This SA supplementation was administered for 5 days (i.e., from the day of infection (day 0) to 4 days post-infection (day 4). During the 2 weeks post-infection, supplementation with SA had no effect (P > 0.05) on growth performances nor on fecal scores. A significant SA × time interaction (P < 0.01) for fecal scores and the percentage of diarrhea indicated that piglets with SA did not recover faster and did have a second episode of diarrhea. In contrast to SA treatment, inclusion of CE increased (P < 0.05) growth performances and feed intake. In the first week post-infection, CE decreased (P < 0.001) the overall fecal scores, the percentage of piglets with diarrhea, the days in diarrhea, and ETEC shedding in the feces. There was a SA×CE interaction (P < 0.05) for ETEC shedding, suggesting a negative effect of combining SA with CE. This study highlighted that, in contrast to SA, CE could represent a promising alternative to antibiotics immediately after weaning for improving growth performance and reducing PWD.

Development of Bacterial Therapeutics against the Bovine Respiratory Pathogen Mannheimia haemolytica.

Bovine respiratory disease (BRD) is a major cause of morbidity and mortality in beef cattle. Recent evidence suggests that commensal bacteria of the bovine nasopharynx have an important role in maintaining respiratory health by providing colonization resistance against pathogens. The objective of this study was to screen and select bacterial therapeutic candidates from the nasopharynxes of feedlot cattle to mitigate the BRD pathogen Mannheimia haemolytica In a stepwise approach, bacteria (n = 300) isolated from the nasopharynxes of 100 healthy feedlot cattle were identified and initially screened (n = 178 isolates from 12 different genera) for growth inhibition of M. haemolytica Subsequently, selected isolates were evaluated for the ability to adhere to bovine turbinate (BT) cells (n = 47), compete against M. haemolytica for BT cell adherence (n = 15), and modulate gene expression in BT cells (n = 10). Lactobacillus strains had the strongest inhibition of M. haemolytica, with 88% of the isolates (n =33) having inhibition zones ranging from 17 to 23 mm. Adherence to BT cells ranged from 3.4 to 8.0 log10 CFU per 105 BT cells. All the isolates tested in competition assays reduced M. haemolytica adherence to BT cells (32% to 78%). Among 84 bovine genes evaluated, selected isolates upregulated expression of interleukin 8 (IL-8) and IL-6 (P < 0.05). After ranking isolates for greatest inhibition, adhesion, competition, and immunomodulation properties, 6 Lactobacillus strains from 4 different species were selected as the best candidates for further development as intranasal bacterial therapeutics to mitigate M. haemolytica infection in feedlot cattle.IMPORTANCE Bovine respiratory disease (BRD) is a significant animal health issue impacting the beef industry. Current BRD prevention strategies rely mainly on metaphylactic use of antimicrobials when cattle enter feedlots. However, a recent increase in BRD-associated bacterial pathogens that are resistant to metaphylactic antimicrobials highlights a pressing need for the development of novel mitigation strategies. Based upon previous research showing the importance of respiratory commensal bacteria in protecting against bronchopneumonia, this study aimed to develop bacterial therapeutics that could be used to mitigate the BRD pathogen Mannheimia haemolytica Bacteria isolated from the respiratory tracts of healthy cattle were characterized for their inhibitory, adhesive, and immunomodulatory properties. In total, 6 strains were identified as having the best properties for use as intranasal therapeutics to inhibit M. haemolytica If successful in vivo, these strains offer an alternative to metaphylactic antimicrobial use in feedlot cattle for mitigating BRD.

Antimicrobial Drug Administration and Antimicrobial Resistance of Salmonella Isolates Originating from the Broiler Production Value Chain in Nigeria.

Salmonella is among the pathogens on the high global priority lists for monitoring for studies on the discovery of new antimicrobials and understanding of how antimicrobial resistance (AMR) develops. AMR in connection with antibiotic usage patterns has been considered as a strong factor and contributor to the AMR pool. The purposes of use, pattern of antimicrobial drug administration, as well as the prevalence of AMR in Salmonella originating from the Nigeria broiler production value chain (NBPVC) was explored. A well-structured questionnaire on antimicrobial usage (n = 181) was used for sampling that focused on 21 antimicrobials from 151 locations. Simultaneously, AMR testing for 18 commonly used antimicrobials on Salmonella in humans was also carried out. Antimicrobial resistance Salmonella spp. were isolated in 23% of the samples (261 of 1135 samples from the broiler input, products, and the environment) using modified ISO 6579 and invA PCR protocols. Over 80% of the antimicrobials used in the NBPVC were administered without a veterinarian prescription. Prevalence of antimicrobial administration without prescription were as follows: live-bird-market (100%), hatchery (86.7%), grow-out-farm (75%), and breeder (66.7%). Widespread prophylactic and metaphylactic use of antimicrobials were recorded with the highest use seen for enrofloxacin (63% and 24%), tetracycline (58% and 33%), and erythromycin (50% and 17%). Antimicrobial resistance was highest for flumequine (100%), penicillin (95%), and perfloxacin (89%). High levels of use without laboratory support of a newer generation of a class of antibiotics suspected to confer high resistance on older generations of the same class (quinolones) was observed.

Administration of granulocyte-colony stimulating factor (G-CSF) to pigs results in a longer mean survival time after exposure to Streptococcus suis

The use of immunomodulators is a promising alternative to the use of antibiotics for therapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease. Previously we demonstrated a replication-defective adenovirus vector that expresses porcine granulocyte colony-stimulating factor (G-CSF) elicited a sustained neutrophilia, lasting nearly 3 weeks, which may be beneficial to prevent bacterial diseases during times of peak incidence. In a pilot study using the vectored G-CSF with a Caesarian-derived, colostrum-deprived (CDCD) pig model of Streptococcus suis disease, only 1 of 4 pigs given G-CSF developed disease, while 3 of 4 non-treated pigs developed Streptococcal disease. In a subsequent study using a larger number of pigs, although there was no difference in overall survival, there was a longer mean survival time in G-CSF treated pigs. S. suis infection is more severe in CDCD pigs than conventionally raised pigs, consequently results in the field may be superior to the ones reported in this study. Although there were positive effects from the use of G-CSF in this study, further research is needed to determine if improved clinical outcomes could be achieved under field conditions and whether the use of G-CSF in pigs to induce a sustained increase in circulating neutrophil numbers may be useful as an adjunct to antibiotics to diminish the severity of Streptococcal disease, especially during times of stress and pathogen exposure such as post-weaning.

Effects of innate immune stimulation on naturally occurring respiratory disease in beef calves

Stress- and virus-induced immunosuppression are considered major risk factors for the development of bovine respiratory disease (BRD) in beef calves. Although vaccines and the metaphylactic use of antibiotics are available to minimize BRD in herds, it continues to be the leading cause of morbidity in feedlot calves. Research in mice found that lethal bacterial pneumonia was prevented by stimulating the innate immune system. The purpose of this study was to determine if stimulation of innate immune responses on arrival to a feedlot could decrease the prevalence and severity of naturally occurring BRD in beef calves.

A mixed treatment comparison meta-analysis of metaphylaxis treatments for bovine respiratory disease in beef cattle.

The objective of this project was to evaluate the effects of antimicrobials approved for parenteral metaphylactic use in feeder and stocker calves on morbidity and mortality for bovine respiratory disease with the use of a mixed treatment comparison meta-analysis. An initial literature review was conducted in April 2016 through Pubmed, Agricola, and CAB (Commonwealth Agricultural Bureau) for randomized controlled trials for metaphylaxis antimicrobial administered parentally to incoming feedlot or stocker calves within 48 h of arrival. The final list of publications included 29 studies, with a total of 37 trials. There were 8 different metaphylactic antimicrobials. Final event outcomes were categorized into bovine respiratory disease (BRD) morbidity cumulative incidence d 1 to ≤ 60 of the feeding period, BRD morbidity cumulative incidence d 1 to closeout of the feeding period, BRD mortality cumulative incidence d 1 to closeout of the feeding period, and BRD retreatment cumulative incidence morbidity d 1 to closeout of the feeding period. Network meta-analysis combined direct and indirect evidence for all the event outcomes to determine mean odds ratio (OR) with 95% credibility intervals (CrIs) for all metaphylactic antimicrobial comparisons. The "upper tier" treatment arms for morbidity d 1 to ≤ 60 included tulathromycin, gamithromycin, and tilmicosin. For BRD mortality cumulative incidence d 1 to closeout and BRD retreatment morbidity d 1 to closeout, classifying the treatment arms into tiers was not possible due to overlapping 95% CrIs. The results of this project accurately identified differences between metaphylactic antimicrobials, and metaphylactic antimicrobial options appear to offer different outcomes on BRD morbidity and mortality odds in feedlot cattle.

Implementation of a vaccine against Shigatoxin 2e in a piglet producing farm with problems of Oedema disease: case study.

Oedema disease is one of the major diseases in pigs during the nursery period. It is caused by Shigatoxin 2e producing strains of Escherichia coli. In order to combat the disease, the metaphylactic use of colistin sulphate and zinc oxide is widely spread. Additionally, special feeding regimens such as the reduction of the amount of crude protein and the increase of the amount of crude fibre are applied. The goal of this study was to test the efficacy of a vaccine against Oedema disease caused by Shigatoxin 2e in a field trial on a farm with a history of Oedema disease in nursery pigs.The study was carried out on a Dutch farm with 600 sows and a one-week farrowing rhythm and lasted for the time of one year. During this time all piglets were vaccinated with 1 ml ECOPORC SHIGA at the average age of 4 days. The parameters Overall mortality, use of antimicrobials in general, calculated as defined daily dose per animal, use of colistin sulphate and the weight gain were evaluated for all nursery pigs and compared to historical data of animals from the same period of time directly prior to the study serving as a historical control group.The previous mortality in the nursery of 7.7% was significantly reduced to 1.3% after vaccination. The metaphylactic use of colistin sulphate during the nursery period was stopped during the study because no deaths due to Oedema disease had occurred anymore after beginning of vaccination. The defined daily dose per animal per month was significantly reduced from a mean of 1.050 in the year 2012 to a mean of 0.215 in the year 2013. The defined daily dose per animal per year was therefore relevantly reduced from 12.6 in 2012 to 2.6 in 2013.These results show that on this farm Oedema disease can not only be controlled successfully by vaccination but also that vaccination can significantly reduce the use of antimicrobials in the nursery period.

Non-inferiority of nitric oxide releasing intranasal spray compared to sub-therapeutic antibiotics to reduce incidence of undifferentiated fever and bovine respiratory disease complex in low to moderate risk beef cattle arriving at a commercial feedlot

Undifferentiated fever, or bovine respiratory disease complex (BRDc), is a challenging multi-factorial health issue caused by viral/bacterial pathogens and stressors linked to the transport and mixing of cattle, negatively impacting the cattle feedlot industry. Common practice during processing at feedlots is administration of antibiotic metaphylaxis to reduce the incidence of BRDc. Nitric oxide (NO) is a naturally occurring nano-molecule with a wide range of physiological attributes. This study evaluated the metaphylactic use of intranasal NO releasing spray (NORS) to control BRDc incidence in calves at low-moderate risk of developing BRDc, arriving at a commercial feedlot as compared to conventional antibiotic metaphylaxis. One thousand and eighty crossbred, multiple-sourced, commingled, commercial, weaned beef calves were screened, enrolled, randomized and treated upon arrival. Animals appearing sick were pulled (from their pen) by blinded pen keepers then assessed for BRDc symptoms; blood samples were taken for haptoglobin quantification and the animals were rescued with an antibiotic. After 35 days both groups showed no significant difference in BRDc incidence (5.2% of animals from NORS group and 3.2% from antibiotic group). Average daily weight gain of animals at day 150 for the NORS cohort was 1.17kg compared to 1.18kg for the antibiotic group (p>0.05). There was no significant difference in mortality in the first 35 days (p=0.7552), however, general mortality over 150 days trended higher in the antibiotic cohort. NORS treatment was shown to be safe, causing neither distress nor adverse effects on the animals. This large randomized controlled study in low-moderate BRDc incidence risk calves demonstrates that NORS treatment, as compared to conventional metaphylactic antibiotics, is non-inferior based on BRDc incidence and other metrics like weight and mortality. These data justify further studies in higher BRDc incidence risk populations to evaluate NORS as an alternative strategy to reduce sub-therapeutic metaphylaxis antibiotic use in beef cattle production.