Antimicrobial use (AMU) is increasingly threatened by antimicrobial resistance (AMR). The FDA is implementing risk mitigation measures promoting prudent AMU in food animals. Their evaluation is crucial: the AMU/AMR relationship is complex; a suitable framework to analyze interventions is unavailable. Systems science analysis, depicting variables and their associations, would help integrate mathematics/epidemiology to evaluate the relationship. This would identify informative data and models to evaluate interventions. This National Institute for Mathematical and Biological Synthesis AMR Working Group's report proposes a system framework to address the methodological gap linking livestock AMU and AMR in foodborne bacteria. It could evaluate how AMU (and interventions) impact AMR. We will evaluate pharmacokinetic/dynamic modeling techniques for projecting AMR selection pressure on enteric bacteria. We study two methods to model phenotypic AMR changes in bacteria in the food supply and evolutionary genotypic analyses determining molecular changes in phenotypic AMR. Systems science analysis integrates the methods, showing how resistance in the food supply is explained by AMU and concurrent factors influencing the whole system. This process is updated with data and techniques to improve prediction and inform improvements for AMU/AMR surveillance. Our proposed framework reflects both the AMR system's complexity, and desire for simple, reliable conclusions.

The rise in antimicrobial resistance (AMR) poses a major threat to animal agriculture and human health. To summarize and update current and emerging AMR issues that are significant for animal health and food safety, this issue presents a virtual AMR symposium consisting of seven review papers. These reviews cover a newly described AMR mechanism in Campylobacter, effects of AMR and microbiome on Campylobacter infection, plasmid-mediated colistin resistance in food-producing animals, the impact of point source or antibiotic residues on the environmental resistome, and potential factors influencing horizontal gene transfer in the intestines of food animals. These papers also identify significant knowledge gaps in AMR research and provide new directions for the development of innovative and effective strategies to mitigate AMR in the animal production system.

Campylobacter is a major foodborne pathogen and is commonly present in food producing animals. This pathogenic organism is highly adaptable and has become increasingly resistant to various antibiotics. Recently, both the Centers for Disease Control and Prevention and the World Health Organization have designated antibiotic-resistant Campylobacter as a serious threat to public health. For the past decade, multiple mechanisms conferring resistance to clinically important antibiotics have been described in Campylobacter, and new resistance mechanisms constantly emerge in the pathogen. Some of the recent examples include the erm(B) gene conferring macrolide resistance, the cfr(C) genes mediating resistance to florfenicol and other antimicrobials, and a functionally enhanced variant of the multidrug resistance efflux pump, CmeABC. The continued emergence of new resistance mechanisms illustrates the extraordinary adaptability of Campylobacter to antibiotic selection pressure and demonstrate the need for innovative strategies to control antibiotic-resistant Campylobacter. In this review, we will briefly summarize the trends of antibiotic resistance in Campylobacter and discuss the mechanisms of resistance to antibiotics used for animal production and important for clinical therapy in humans. A special emphasis will be given to the newly discovered antibiotic resistance.

With the increase in regulations regarding the use of antibiotic growth promoters and the rise in consumer demand for poultry products from ‘Raised Without Antibiotics’ or ‘No Antibiotics Ever’ flocks, the quest for alternative products or approaches has intensified in recent years. A great deal of research has focused on the development of antibiotic alternatives to maintain or improve poultry health and performance. This review describes the potential for the various alternatives available to increase animal productivity and help poultry perform to their genetic potential under existing commercial conditions. The classes of alternatives described include probiotics, prebiotics, synbiotics, organic acids, enzymes, phytogenics, antimicrobial peptides, hyperimmune egg antibodies, bacteriophages, clay, and metals. A brief description of the mechanism of action, efficacy, and advantages and disadvantages of their uses are also presented. Though the beneficial effects of many of the alternatives developed have been well demonstrated, the general consensus is that these products lack consistency and the results vary greatly from farm to farm. Furthermore, their mode of action needs to be better defined. Optimal combinations of various alternatives coupled with good management and husbandry practices will be the key to maximize performance and maintain animal productivity, while we move forward with the ultimate goal of reducing antibiotic use in the animal industry.

Campylobacter jejuni is an important zoonotic pathogen recently designated a serious antimicrobial resistant (AR) threat. While most patients with C. jejuni experience hemorrhagic colitis, serious autoimmune conditions can follow including inflammatory bowel disease (IBD) and the acute neuropathy Guillain Barré Syndrome (GBS). This review examines inter-relationships among factors mediating C. jejuni diarrheal versus autoimmune disease especially AR C. jejuni and microbiome shifts. Because both susceptible and AR C. jejuni are acquired from animals or their products, we consider their role in harboring strains. Inter-relationships among factors mediating C. jejuni colonization, diarrheal and autoimmune disease include C. jejuni virulence factors and AR, the enteric microbiome, and host responses. Because AR C. jejuni have been suggested to affect the severity of disease, length of infections and propensity to develop GBS, it is important to understand how these interactions occur when strains are under selection by antimicrobials. More work is needed to elucidate host–pathogen interactions of AR C. jejuni compared with susceptible strains and how AR C. jejuni are maintained and evolve in animal reservoirs and the extent of transmission to humans. These knowledge gaps impair the development of effective strategies to prevent the emergence of AR C. jejuni in reservoir species and human populations.

For several billion years, bacteria have developed mechanisms to resist antibacterial substances. In modern time, antibiotics are frequently used in veterinary and human medicine for prevention and treatment of diseases, globally still also for their growth promoting effects as feed additives. This complex situation has evolved in accelerating development and prevalence of multi-drug resistant bacteria in livestock and people. Extended-spectrum beta-lactamase (ESBL) producing bacteria are resistant to a wide range of ß-lactam antibiotics. They are currently considered as one of the main threats for the treatment of infections in humans and animals. In livestock and animal products, poultry and poultry products show the highest prevalence of ESBL-producers with CTX-M-1, TEM-52 and SHV-12 being the most common ESBL-types in poultry. Escherichia coli and Salmonella spp. are the bacteria in poultry, which carry ESBL-genes most frequently. ESBL-producing bacteria are present at every level of the poultry production pyramid and can be detected even in the meconium of newly hatched chicks. The environment close to poultry barns shows high prevalence rates of these bacteria and contributes to an ongoing infection pressure with further ESBL-types. Probiotics have been shown to successfully reduce ESBL-producers in chicken, as well as ESBL-gene transfer. Other feed additives, such as zinc and copper, increase the prevalence of ESBL-producing bacteria when fed to animals. To our best knowledge, this is the first publication presenting a comparative overview of the prevalence of ESBL-types using data from different countries. To reduce the hazard for public health from poultry carrying high numbers of ESBL-producers, preventive measurements must include the surrounding environment and avoidance of antibiotic usage at all levels of the production pyramid. The first results, of the research on the impact of feed additives on the spread of ESBL-genes, indicate the diet as a further, possible magnitude of influence.

There is a growing concern about the role of the environment in the dissemination of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this systematic review, we summarize evidence for increases of ARG in the natural environment associated with potential sources of ARB and ARG such as agricultural facilities and wastewater treatment plants. A total of 5247 citations were identified, including studies that ascertained both ARG and ARB outcomes. All studies were screened for relevance to the question and methodology. This paper summarizes the evidence only for those studies with ARG outcomes (n = 24). Sixteen studies were at high (n = 3) or at unclear (n = 13) risk of bias in the estimation of source effects due to lack of information or failure to control for confounders. Statistical methods were used in nine studies; three studies assessed the effect of multiple sources using modeling approaches, and none reported effect measures. Most studies reported higher ARG concentration downstream/near the source, but heterogeneous findings hindered making any sound conclusions. To quantify increases of ARG in the environment due to specific point sources, there is a need for studies that emphasize analytic or design control of confounding, and that provide effect measure estimates.

Bovine mastitis is an important animal production disease that affects the dairy industry globally. Studies have estimated the prevalence of this disease in approximately 30% of African countries, with the highest prevalence found in Ethiopia. This is despite the wide cattle distribution in Africa, and the largest number of dairy farms and herds in countries such as South Africa, Kenya and Uganda. Furthermore, the estimated financial losses due to direct and indirect impacts of bovine mastitis are lacking in this continent. Therefore, intensive research efforts will help determine the continent-wide economic impacts and advance careful monitoring of disease prevalence and epidemiology. Here, published cases supporting the occurrence and importance of bovine mastitis in certain regions of Africa are outlined.

Emergence and spread of antimicrobial-resistant bacteria, including extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, have become serious problems worldwide. Recent studies conducted in Vietnam revealed that ESBL-producing E. coli are widely distributed in food animals and people. CTX-M-9 and CTX-M-1 are the most prevalent β-lactamases among the identified ESBLs. Furthermore, most of the ESBL-producing E. coli isolates were multi-drug resistant. Residual antimicrobials such as sulfamethoxazole, trimethoprim, sulfadimidine, cephalexin, and sulfadiazine were also detected at a high level in both animal meats and environmental water collected from several cities, including Ho Chi Minh city and Can Tho city. These recent studies indicated that improper use of antimicrobials in animal-originated food production might contribute to the emergence and high prevalence of ESBL-producing E. coli in Vietnam. Although clonal ESBL-producing E. coli was not identified, CTX-M-55 gene-carrying plasmids with similar sizes (105–139 kb) have been commonly detected in the ESBL-producing E. coli strains isolated from various food animals and human beings. This finding strongly suggests that horizontal transfer of the CTX-M plasmid among various E. coli strains played a critical role in the emergence and high prevalence of ESBL-producing E. coli in Vietnam.

The poultry industry faces challenge amidst global food security crisis. Infectious bronchitis is one of the most important viral infections that cause huge economic loss to the poultry industry worldwide. The causative agent, infectious bronchitis virus (IBV) is an RNA virus with great ability for mutation and recombination; thus, capable of generating new virus strains that are difficult to control. There are many IBV strains found worldwide, including the Massachusetts, 4/91, D274, and QX-like strains that can be grouped under the classic or variant serotypes. Currently, information on the epidemiology, strain diversity, and global distribution of IBV has not been comprehensively reported. This review is an update of current knowledge on the distribution, genetic relationship, and diversity of the IBV strains found worldwide.

Colistin, a peptide antibiotic belonging to the polymyxin family, is one of the last effective drugs for the treatment of multidrug resistant Gram-negative infections. Recent discovery of a novel mobile colistin resistance gene, mcr-1, from people and food animals has caused a significant public health concern and drawn worldwide attention. Extensive usage of colistin in food animals has been proposed as a major driving force for the emergence and transmission of mcr-1; thus, there is a worldwide trend to limit colistin usage in animal production. However, despite lack of colistin usage in food animals in the USA, mcr-1-positive Escherichia coli isolates were still isolated from swine. In this paper, we provided an overview of colistin usage and epidemiology of mcr-1 in food animals, and summarized the current status of mechanistic and evolutionary studies of the plasmid-mediated colistin resistance. Based on published information, we further discussed several non-colistin usage risk factors that may contribute to the persistence, transmission, and emergence of colistin resistance in an animal production system. Filling the knowledge gaps identified in this review is critical for risk assessment and risk management of colistin resistance, which will facilitate proactive and effective strategies to mitigate colistin resistance in future animal production systems.

Antibiotic resistance (AR) is ancient. Use of antibiotics is a selective driving force that enriches AR genes and promotes the emergence of resistant pathogens. It also has been widely accepted that horizontal gene transfer (HGT) occurs everywhere and plays a critical role in the transmission of AR genes among bacteria. However, our understanding of HGT processes primarily build on extensive in vitro studies; to date, there is still a significant knowledge gap regarding in situ HGT events as well as the factors that influence HGT in different ecological niches. This review is focused on the HGT process in the intestinal tract, a ‘melting pot’ for gene exchange. Several factors that potentially influence in vivo HGT efficiency in the intestine are identified and summarized, which include SOS-inducing agents, stress hormones, microbiota and microbiota-derived factors. We highlight recent discoveries demonstrating that certain antibiotics, which are widely used in animal industry, can enhance HGT in the intestine by serving as DNA-damaging, SOS-inducing agents. Despite recent progress, research on in vivo HGT events is still in its infancy. A better understanding of the factors influencing HGT in the intestine is highly warranted for developing effective strategies to mitigate AR in animal production as well as in future agricultural ecosystems.

Addition of sub-therapeutic antibiotics to the feed of food-producing animals for growth promotion and disease prevention has become a common agricultural practice in many countries. The emergence of antibiotic-resistant pathogens is a looming concern associated with the use of antibiotic growth promoters (AGPs) around the world. In addition, some studies have shown that AGPs may not only affect antibiotic resistance but may also stimulate the dissemination of virulence factors via bacteriophages. Although only a few studies are currently available in the literature regarding this topic, in this article we endeavor to provide a perspective about how AGPs would impact the transmission of virulence factors by horizontal gene transfer via phages in a few pathogenic bacterial species significant to livestock production.

The supplementation of livestock rations with herbs containing bioactive components, such as rosmarinic acid (RA), have shown promising results as a natural feed additive in promoting growth, productive and reproductive performance, feed utilization, fertility, anti-oxidant status and immunologic indices. Furthermore, RA reportedly reduces the risks of various animal diseases and mitigates side effects of chemical and synthetic drugs. RA is a natural polyphenol present in several Lamiaceae herbs like Perilla frutescens, and RA is becoming an integral component of animal nutrition as it counters the effect of reactive oxygen species induced in the body as a consequence of different kinds of stressors. Studies have further ascertained the capability of RA to work as an anti-microbial, immunomodulatory, anti-diabetic, anti-allergic, anti-inflammatory, hepato- and renal-protectant agent, as well as to have beneficial effects during skin afflictions. Additionally, RA is favored in meat industries due to enhancing the quality of meat products by reportedly improving shelf-life and imparting desirable flavor. This review describes the beneficial applications and recent findings with RA, including its natural sources, modes of action and various useful applications in safeguarding livestock health as well as important aspects of human health.

Acupuncture has become increasingly popular in veterinary medicine. Within the scientific literature there is debate regarding its efficacy. Due to the complex nature of acupuncture, a scoping review was undertaken to identify and categorize the evidence related to acupuncture in companion animals (dogs, cats, and horses). Our search identified 843 relevant citations. Narrative reviews represented the largest proportion of studies (43%). We identified 179 experimental studies and 175 case reports/case series that examined the efficacy of acupuncture. Dogs were the most common subjects in the experimental trials. The most common indication for use was musculoskeletal conditions, and the most commonly evaluated outcome categories among experimental trials were pain and cardiovascular parameters. The limited number of controlled trials and the breadth of indications for use, outcome categories, and types of acupuncture evaluated present challenges for future systematic reviews or meta-analyses. There is a need for high-quality randomized controlled trials addressing the most common clinical uses of acupuncture, and using consistent and clinically relevant outcomes, to inform conclusions regarding the efficacy of acupuncture in companion animals.