Fine-tuning of post-weaning pig microbiome structure and functionality by in-feed zinc oxide and antibiotics use.

Introduction: Post-weaning diarrhoea (PWD) is a multifactorial disease that affects piglets after weaning, contributing to productive and economic losses. Its control includes the use of in-feed prophylactic antibiotics and therapeutic zinc oxide (ZnO), treatments that, since 2022, are no longer permitted in the European Union due to spread of antimicrobial resistance genes and pollution of soil with heavy metals. A dysbiosis in the microbiota has been suggested as a potential risk factor of PWD onset. Understanding pig's microbiota development around weaning and its changes in response to ZnO and antibiotics is crucial to develop feasible alternatives to prophylactic and metaphylactic antimicrobial use. Methods: This study used shotgun metagenomic sequencing to investigate the environmental and faecal microbiota on 10 farms using (Treated) or not using (ZnO-free) in-feed antibiotics and ZnO during the first 14 days post-weaning (dpw). Environmental samples from clean pens were collected at weaning day (0dpw), and faecal samples at 0, 7 and 14dpw. Diarrhoeic faecal samples were collected at 7dpw when available. Results: The analysis of data revealed that the faecal microbiota composition and its functionality was impacted by the sampling time point (microbiota maturation after weaning) but not by the farm environment. Treatment with antibiotics and ZnO showed no effects on diversity indices while the analyses of microbiota taxonomic and functional profiles revealed increased abundance of taxa and metabolic functions associated with Phascolarctobacterium succinatutens or different species of Prevotella spp. on the Treated farms, and with Megasphaera elsdenii and Escherichia coli on the ZnO-free farms. The analysis of diarrhoea samples revealed that the treatment favoured the microbiota transition or maturation from 0dpw to 14dpw in Treated farms, resembling the composition of healthy animals, when compared to diarrhoea from ZnO-free farms, which were linked in composition to 0dpw samples. Discussion: The results provide a comprehensive overview of the beneficial effects of ZnO and antibiotics in PWD in the microbiota transition after weaning, preventing the overgrowth of pathogens such as pathogenic E. coli and revealing the key aspects in microbiota maturation that antibiotics or ZnO alternatives should fulfil.

Antimicrobial Resistance in Commensal Escherichia coli of the Porcine Gastrointestinal Tract.

Antimicrobial resistance (AMR) in Escherichia coli of animal origin presents a threat to human health. Although animals are not the primary source of human infections, humans may be exposed to AMR E. coli of animal origin and their AMR genes through the food chain, direct contact with animals, and via the environment. For this reason, AMR in E. coli from food producing animals is included in most national and international AMR monitoring programmes and is the subject of a large body of research. As pig farming is one of the largest livestock sectors and the one with the highest antimicrobial use, there is considerable interest in the epidemiology of AMR in E. coli of porcine origin. This literature review presents an overview and appraisal of current knowledge of AMR in commensal E. coli of the porcine gastrointestinal tract with a focus on its evolution during the pig lifecycle and the relationship with antimicrobial use. It also presents an overview of the epidemiology of resistance to extended spectrum cephalosporins, fluoroquinolones, and colistin in pig production. The review highlights the widespread nature of AMR in the porcine commensal E. coli population, especially to the most-used classes in pig farming and discusses the complex interplay between age and antimicrobial use during the pig lifecycle.

Antimicrobial resistance in Escherichia coli isolated from on-farm and conventional hatching broiler farms in Ireland.

BACKGROUND: On-farm hatching (OH) systems are becoming more common in broiler production. Hatching conditions differ from conventional farms as OH chicks avoid exposure to handling, transport, post-hatch water and feed deprivation. In contrast, chicks in conventional hatching conditions (CH) are exposed to standard hatchery procedures and transported post hatching. The objectives of this pilot study were to investigate the prevalence and frequency of Escherichia coli resistant to antimicrobials, including presumptive ESBL/AmpC-producing E. coli, isolated from environmental and faecal samples from OH versus CH hatching systems, and to investigate the presence of ESBL/AmpC-producing encoding genes. RESULTS: Environmental samples were collected from one flock in 10 poultry farms (5 OH farms, 5 CH farms) on day 0 post disinfection of the facilities to assess hygiene standards. On D10 and D21 post egg/chick arrival onto the farm, samples of faeces, boot swabs and water drinker lines were collected. E. coli were isolated on MacConkey agar (MC) and MacConkey supplemented with cefotaxime (MC+). Few E. coli were detected on D0. However, on D10 and D21 E. coli isolates were recovered from faeces and boot swabs. Water samples had minimal contamination. In this study, 100% of cefotaxime resistant E. coli isolates (n=33) detected on selective media and 44% of E. coli isolates (84/192) detected on nonselective media were multidrug resistant (MDR). The antimicrobial resistance (AMR) genotype for the 15 ESBL/AmpC producing isolates was determined using multiplex PCR. Six of these were selected for Sanger sequencing of which two were positive for blaCMY-2, two for blaTEM-1 and two were positive for both genes. CONCLUSIONS: There was no difference in E. coli isolation rates or prevalence of AMR found between the OH versus CH systems, suggesting that the OH system may not be an additional risk of resistant E. coli dissemination to broilers compared to the CH systems. The frequency of ß-lactam resistant E. coli in boot swab and faeces samples across both OH (24/33 (73%)) and CH (9/33 (27%)) systems may indicate that hatcheries could be a reservoir and major contributor to the transmission of AMR bacteria to flocks after entry to the rearing farms.

Risk Factors for Antimicrobial Use on Irish Pig Farms.

The threat to public health posed by antimicrobial resistance in livestock production means that the pig sector is a particular focus for efforts to reduce antimicrobial use (AMU). This study sought to investigate the risk factors for AMU in Irish pig production. Antimicrobial use data were collected from 52 farrow-to-finish farms. The risk factors investigated were farm characteristics and performance, biosecurity practices, prevalence of pluck lesions at slaughter and serological status for four common respiratory pathogens and vaccination and prophylactic AMU practices. Linear regression models were used for quantitative AMU analysis and risk factors for specific AMU practices were investigated using logistic regression. Farms that milled their own feed had lower total AMU (p < 0.001), whereas higher finisher mortality (p = 0.043) and vaccinating for swine influenza (p < 0.001) increased AMU. Farms with higher prevalence of pericarditis (p = 0.037) and lung abscesses (p = 0.046) used more group treatments. Farms with higher prevalence of liver milk spot lesions (p = 0.018) and farms practising prophylactic AMU in piglets (p = 0.03) had higher numbers of individual treatments. Farms practising prophylactic AMU in piglets (p = 0.002) or sows (p = 0.062) had higher use of cephalosporins and fluoroquinolones. This study identified prophylactic use and respiratory disease as the main drivers for AMU in Irish pig production. These findings highlight areas of farm management where interventions may aid in reducing AMU on Irish pig farms.

Informing National Health Service patients about participation in clinical research: A comparison of opt-in and opt-out approaches across the United Kingdom.

OBJECTIVE: Recruitment to clinical research in the National Health Service remains challenging. One barrier is accessing patients to discuss research participation. Two general approaches are used in the United Kingdom to facilitate this: an 'opt-in' approach (when clinicians communicate research opportunities to patients) and an 'opt-out' approach (all patients have the right to be informed of relevant research opportunities). No evidence-based data are available, however, to inform the decision about which approach is preferable. This study aimed to collect information from 'opt-in' and 'opt-out' Trusts and identify which of the two approaches is optimal for ensuring National Health Service patients are given opportunities to discuss research participation. METHOD: This sequential mixed methods study comprised three phases: (1) an Appreciative Inquiry across UK Trusts, (2) online surveys and (3) focus groups with National Health Service staff and patients at a representative mental health Trust. RESULTS: The study was conducted between June and October 2019. Out of seven National Health Service Mental Health Trusts contacted (three 'opt-out' and four 'opt-in'), only four took part in phase 1 of the study and three of them were 'opt-out' Trusts. Benefits of an 'opt-out' approach included greater inclusivity of patients and the removal of research gatekeepers, while the involvement of research-active clinicians and established patient-clinician relationships were cited as important to 'opt-in' success. Phases 2 and 3 were conducted at a different Trust (Oxford Health NHS Foundation Trust) which was using an 'opt-in' approach. Of 333 staff and member survey responders, 267 (80.2%) favoured moving to an 'opt-out' approach (phase 2). Nineteen staff and 16 patients and carers participated in focus groups (phase 3). Concern was raised by staff regarding the lack of time for clinical research, with clinical work taking precedence over research; patients were concerned about a lack of research activity; all considered research to be beneficial and were supportive of a move to 'opt-out'. CONCLUSION: Findings suggest that 'opt-out' is more beneficial than 'opt-in', with the potential to vastly increase patient access to research opportunities and to enable greater equality of information provision for currently marginalised groups. This should ensure that healthcare research is more representative of the entire population, including those with a mental health diagnosis.

Does the Use of Different Indicators to Benchmark Antimicrobial Use Affect Farm Ranking?

The need to reduce antimicrobial use (AMU) in livestock production has led to the establishment of national AMU data collection systems in several countries. However, there is currently no consensus on which AMU indicator should be used and many of the systems have defined their own indicators. This study sought to explore the effect of using different internationally recognized indicators on AMU data collected from Irish pig farms and to determine if they influenced the ranking of farms in a benchmarking system. AMU data for 2016 was collected from 67 pig farms (c. 35% of Irish pig production). Benchmarks were defined using seven AMU indicators: two based on weight of active ingredient; four based on the defined daily doses (DDD) used by the European Medicines Agency and the national monitoring systems of Denmark and the Netherlands; and one based on the treatment incidence (TI200) used in several published studies. An arbitrary "action zone," characterized by farms above an acceptable level of AMU, was set to the upper quartile (i.e., the top 25% of users, n = 17). Each pair of indicators was compared by calculating the Spearman rank correlation and assessing if farms above the threshold for one indicator were also above it for the comparison indicator. The action zone was broadly conserved across all indicators; even when using weight-based indicators. The lowest correlation between indicators was 0.94. Fifteen farms were above the action threshold for at least 6 of the 7 indicators while 10 farms were above the threshold for all indicators. However, there were important differences noted for individual farms between most pairs of indicators. The biggest discrepancies were seen when comparing the TI200 to the weight-based indicators and the TI200 to the DDDANED (as used by Dutch AMU monitoring system). Indicators using the same numerator were the most similar. All indicators used in this study identified the majority of high users. However, the discrepancies noted highlight the fact that different methods of measuring AMU can affect a benchmarking system. Therefore, careful consideration should be given to the limitations of any indicator chosen for use in an AMU monitoring system.

Quantification, description and international comparison of antimicrobial use on Irish pig farms.

BACKGROUND: There is concern that the use of antimicrobials in livestock production has a role in the emergence and dissemination of antimicrobial resistance in animals and humans. Consequently, there are increasing efforts to reduce antimicrobial use (AMU) in agriculture. As the largest consumer of veterinary antimicrobials in several countries, the pig sector is a particular focus of these efforts. Data on AMU in pig production in Ireland are lacking. This study aimed to quantify AMU on Irish pig farms, to identify the major patterns of use employed and to compare the results obtained to those from other published reports and studies. RESULTS: Antimicrobial use data for 2016 was collected from 67 Irish pig farms which represented c. 35% of national production. The combined sample population consumed 14.5 t of antimicrobial by weight of active ingredient suggesting that the pig sector accounted for approximately 40% of veterinary AMU in Ireland in 2016. At farm level, median AMU measured in milligram per population correction unit (mg/PCU) was 93.9 (range: 1.0-1196.0). When measured in terms of treatment incidence (TI200), median AMU was 15.4 (range: 0.2-169.2). Oral treatments accounted for 97.5% of all AMU by weight of active ingredient and were primarily administered via medicated feed to pigs in the post weaning stages of production. AMU in Irish pig production in 2016 was higher than results obtained from the national reports of Sweden, Denmark, the Netherlands and France but lower than the United Kingdom. CONCLUSIONS: Pig production in Ireland is an important consumer of veterinary antimicrobials. The quantities and patterns of AMU on Irish pig farms are comparable to pig production in other European countries but higher than some countries with more advanced AMU reduction strategies. This AMU is characterised by a high proportion of prophylactic use and is primarily administered to pigs post weaning via medicated feed. Further studies to better understand the reasons for AMU on Irish pig farms and strategies to improve health among weaner pigs will be of benefit in the effort to reduce AMU.

Current antimicrobial use in farm animals in the Republic of Ireland.

Antimicrobial resistance has been recognised as one of the most difficult challenges facing human and animal health in recent decades. The surveillance of antimicrobial use in animal health plays a major role in dealing with the growing issue of resistance. This paper reviews current data available on antimicrobial use in farmed animals in the Republic of Ireland, including each of the major livestock production sectors; pigs, poultry, dairy, beef and sheep. A systematic literature search was conducted to identify relevant published literature, and ongoing research was identified through the network of authors and searches of each of the research databases of the main agriculture funding bodies in Ireland. The varying quantities and quality of data available across each livestock sector underlines the need for harmonisation of data collection methods. This review highlights the progress that has been made regarding data collection in the intensive production sectors such as pigs and poultry, however, it is clear there are significant knowledge gaps in less intensive industries such as dairy, beef and sheep. To comply with European regulations an antimicrobial data collection system is due to be developed for all food-producing animals in the future, however in the short-term surveillance studies have allowed us to build a picture of current use within the Republic of Ireland. Further studies will allow us to fill current knowledge gaps and build a more comprehensive overview of antimicrobial use in farm animals in Ireland.