New concepts have emerged in the past few years that help us to better understand the emergence and spread of antimicrobial resistance (AMR). These include, among others, the discovery of the mutator state and the concept of mutant selection window for resistances emerging primarily through mutations in existing genes. Our understanding of horizontal gene transfer has also evolved significantly in the past few years, and important new mechanisms of AMR transfer have been discovered, including, among others, integrative conjugative elements and ISCR (insertion sequences with common regions) elements. Simultaneously, large-scale studies have helped us to start comprehending the immense and yet untapped reservoir of both AMR genes and mobile genetic elements present in the environment. Finally, new PCR- and DNA sequencing-based techniques are being developed that will allow us to better understand the epidemiology of classical vectors of AMR genes, such as plasmids, and to monitor them in a more global and systematic way.

The vast literature on antimicrobial drug use in animals has expanded considerably recently as the antimicrobial resistance (AMR) crisis in human medicine leads to questions about all usage of antimicrobial drugs, including long-term usage in intensively managed food animals for growth promotion and disease prevention. Attention is also increasingly focusing on antimicrobial use and on bacterial resistance in companion animals, which are in intimate contact with the human population. They may share resistant bacteria with their owners, amplify resistant bacteria acquired from their owners, and act as a reservoir for human infection. Considerable effort is being made to describe the basis of AMR in bacterial pathogens of animals. Documentation of many aspects of use of antimicrobials in animals is, however, generally less developed and only a few countries can describe quantities of drugs used in animals to kg levels annually. In recent years, many national veterinary associations have produced ‘prudent use guidelines’ to try to improve antimicrobial drug use and decrease resistance, but the impact of guidelines is unknown. Within the evolving global movement for ‘antimicrobial stewardship’, there is considerable scope to improve many aspects of antimicrobial use in animals, including infection control and reduction of use, with a view to reducing resistance and its spread, and to preserving antimicrobial drugs for the future.

Large amounts of antimicrobial agents are still being used in modern swine production in many countries around the world. This facilitates the emergence and development of antimicrobial resistance. Bacteria causing infections in swine have in several cases acquired resistance to a number of the agents most commonly used for treatment, making it difficult to predict the efficacy of different antimicrobial agents without prior susceptibility testing. This review gives an overview of recent susceptibility data from different parts of the world and discusses the importance of the development of resistance not only in the treatment of infections in swine but also taking into account the human health implications of antimicrobial resistance.

This paper reviews the present state of antimicrobial resistance (AMR) in the zoonotic bacteria Salmonella, Campylobacter jejuni and Campylobacter coli, and in Escherichia coli from chickens and turkeys. For Salmonella, the frequencies and patterns of AMR vary depending on time, region, serovar, the particular farm, layers versus broilers, and the antimicrobial agent. There is usually a higher frequency of AMR in Salmonella from turkeys compared with Salmonella from chickens. Clonal and horizontal transmission of AMR occur and there is concern about the spread of transmissible plasmids that encode extended spectrum cephalosporinases. Resistance to fluoroquinolones is generally low. For Campylobacter, resistance to tetracycline is usually at moderate to high frequency, resistance to quinolones/fluoroquinolones varies from low to high, and resistance to macrolides is usually low. There are high levels of fluoroquinolone resistance in some countries. Avian pathogenic E. coli are often highly resistant, especially to tetracycline, streptomycin, and sulfonamides. Plasmid-mediated resistance is common. High levels of resistance to ciprofloxacin have been reported from China. Commensal E. coli from poultry have similar patterns of resistance but at lower frequencies. Integron associated resistance occurs commonly in Salmonella and E. coli but has not been detected in Campylobacter.

Observational studies of cattle production systems usually find that cattle from conventional dairies harbor a higher prevalence of antimicrobial resistant (AMR) enteric bacteria compared to organic dairies or beef-cow operations; given that dairies usually use more antimicrobials, this result is not unexpected. Experimental studies have usually verified that application of antimicrobials leads to at least a transient expansion of AMR bacterial populations in treated cattle. Nevertheless, on dairy farms the majority of antibiotics are used to treat mastitis and yet AMR remains relatively low in mastitis pathogens. Other studies have shown no correlation between antimicrobial use and prevalence of AMR bacteria including documented cases where the prevalence of AMR bacteria is non-responsive to antimicrobial applications or remains relatively high in the absence of antimicrobial use or any other obvious selective pressures. Thus, there are multi-factorial events and pressures that influence AMR bacterial populations in cattle production systems. We introduce a heuristic model that illustrates how repeated antimicrobial selection pressure can increase the probability of genetic linkage between AMR genes and niche- or growth-specific fitness traits. This linkage allows persistence of AMR bacteria at the herd level because subpopulations of AMR bacteria are able to reside long-term within the host animals even in the absence of antimicrobial selection pressure. This model highlights the need for multiple approaches to manage herd health so that the total amount of antimicrobials is limited in a manner that meets animal welfare and public health needs while reducing costs for producers and consumers over the long-term.

Antimicrobial resistance (AMR) is an emerging problem in companion animals, because of difficult-to-treat infections, possible pressure to use antimicrobials that are important in human medicine, and potential zoonotic transmission. The extent and importance of AMR in companion animals are poorly understood, in part because of limited surveillance; however, it is clear that resistance is problematic in many pathogens and commensals, including staphylococci, enterococci, Escherichia coli and Salmonella.

The relative contribution of veterinary and human clinical treatments to the selection of antimicrobial resistance in zoonotic pathogens remains controversial. In this review, we consider bacterial pathogens that differ in host specificity and address their resistance profiles: pathogens that only occur in the human host, pathogens that are specific to particular food-producing animals and pathogens that occur in both host types. Compared with those pathogens restricted to a single animal host, pathogens found in both human and animal hosts appear to have higher incidences of resistance. However, the most urgent and severe resistance problems occur with pathogens exclusively infecting humans. Differences exist in the available genetic repertoire of a bacterial species and these are reflected in the observed resistance patterns; it is important to note that different bacterial species do not automatically result in similarly resistant populations when they undergo comparable selection in different host species. Thus, within a bacterial species, prevalence of resistance can differ between populations isolated from different hosts. For some species, fluctuations in dominant subpopulations, for instance particular serotypes, can be the most important factor determining resistance. The frequently expressed opinion that veterinary use of antimicrobials is at the heart of many resistance problems may be an oversimplification of the complex forces at play.

The prevention of infectious diseases of animals by vaccination has been routinely practiced for decades and has proved to be one of the most cost-effective methods of disease control. However, since the pioneering work of Pasteur in the 1880s, the composition of veterinary vaccines has changed very little from a conceptual perspective and this has, in turn, limited their application in areas such as the control of chronic infectious diseases. New technologies in the areas of vaccine formulation and delivery as well as our increased knowledge of disease pathogenesis and the host responses associated with protection from disease offer promising alternatives for vaccine formulation as well as targets for the prevention of bacterial disease. These new vaccines have the potential to lessen our reliance on antibiotics for disease control, but will only reach their full potential when used in combination with other intervention strategies.

The successful use of virulent (lytic) bacteriophages (phages) in preventing and treating neonatal enterotoxigenic Escherichia coli infections in calves, lambs and pigs has prompted investigation of other applications of phage therapy in food animals. While results have been very variable, some indicate that phage therapy is potentially useful in virulent Salmonella and E. coli infections in chickens, calves and pigs, and in control of the food-borne pathogens Salmonella and Campylobacter jejuni in chickens and E. coli O157:H7 in cattle. However, more rigorous and comprehensive research is required to determine the true potential of phage therapy. Particular challenges include the selection and characterization of phages, practical modes of administration, and development of formulations that maintain the viability of phages for administration. Also, meaningful evaluation of phage therapy will require animal studies that closely represent the intended use, and will include thorough investigation of the emergence and characteristics of phage resistant bacteria. As well, effective use will require understanding the ecology and dynamics of the endemic and therapeutic phages and their interactions with target bacteria in the farm environment. In the event that the potential of phage therapy is realized, adoption will depend on its efficacy and complementarity relative to other interventions. Another potential challenge will be regulatory approval.

The microbial population of the intestinal tract is a complex natural resource that can be utilized in an effort to reduce the impact of pathogenic bacteria that affect animal production and efficiency, as well as the safety of food products. Strategies have been devised to reduce the populations of food-borne pathogenic bacteria in animals at the on-farm stage. Many of these techniques rely on harnessing the natural competitive nature of bacteria to eliminate pathogens that negatively impact animal production or food safety. Thus feed products that are classified as probiotics, prebiotics and competitive exclusion cultures have been utilized as pathogen reduction strategies in food animals with varying degrees of success. The efficacy of these products is often due to specific microbial ecological factors that alter the competitive pressures experienced by the microbial population of the gut. A few products have been shown to be effective under field conditions and many have shown indications of effectiveness under experimental conditions and as a result probiotic products are widely used in all animal species and nearly all production systems. This review explores the ecology behind the efficacy of these products against pathogens found in food animals, including those that enter the food chain and impact human consumers.

Antimicrobial peptides (AMPs) are ubiquitous, gene-encoded natural antibiotics that have gained recent attention in the search for new antimicrobials to combat infectious disease. In multicellular organisms, AMPs, such as defensins and cathelicidins, provide a coordinated protective response against infection and are a principal component of innate immunity in vertebrates. In unicellular organisms, AMPs, such as bacteriocins, function to suppress competitor species. Because many AMPs kill bacteria by disruption of membrane integrity and are thus thought to be less likely to induce resistance, AMPs are being extensively evaluated as novel antimicrobial drugs. This review summarizes and discusses the antibiotic properties of AMPs highlighting their potential as alternatives to conventional antibiotics.

Antimicrobial resistance is a rapidly increasing problem impacting the successful treatment of bacterial infectious disease. To combat resistance, the development of new treatment options is required. Recent advances in technology have aided in the discovery of novel antibacterial agents, specifically through genome mining for novel natural product biosynthetic gene clusters and improved small molecule high-throughput screening methods. Novel targets such as lipopolysaccharide and fatty acid biosyntheses have been identified by essential gene studies, representing a shift from traditional antibiotic targets. Finally, inhibiting non-essential genes with small molecules is being explored as a method for rescuing the activity of ‘old’ antibiotics, providing a novel synergistic approach to antimicrobial discovery.