The current imbalance between AMR programmes and reported data limit the full understanding of an integrated One Health global AMR surveillance system [
16]. In 2015, to address this issue, the Joint Tripartite formed by the Food and Agriculture Organisation of the United Nations, the World Organisation for Animal Health and the WHO adopted a Global Action Plan to ensure worldwide capacity to control and prevent AMR bacterial infectious diseases, with effective and safe medicines used responsibly and accessible to the world population [
17]. Since then, the Joint Tripartite has been working to establish an integrated surveillance system platform to collect and assemble data reported by countries related to human, animal, food and environmental health. They also assess the implementation and development of the Global Action Plan on AMR in all sectors [
17].
Moreover, the EMA categorised antimicrobials according to the risk they pose to public health and the need for their use in veterinary medicine. These are divided into four categories: Category D, which should be used with caution and as a first line of treatment whenever possible; Category C, with antimicrobials that should be used with caution and only when Category D antibiotics fail clinically; Category B, including antimicrobials that are critically important in human medicine and whose use should be restricted in veterinary medicine and adopted only when all therapeutic alternatives (D and C) have been exhausted; and finally, Category A, whose use is limited in human medicine and is not authorised in the European Union (EU) in veterinary medicine and therefore for the treatment of production animals [
20]. However, there are some exceptions in the clinical care of companion animals, because in exceptional situations, antimicrobials from category A could be dispensed and used, hence creating a serious problem [
20].
Moreover, only a few countries submit reports that include AMR in companion animals that live in close contact with humans and are considered an important potential source of AMR. These established AMR Surveillance Programmes are mainly focused on AMR prevalence in pathogenic bacteria [
10]. In this sense,
Staphylococcus pseudintermedius as well as
Staphylococcus aureus are coagulase-positive species of
Staphylococcus. These bacterial species are opportunistic pathogens found in the mucous membranes of animals as part of the commensal bacteria and have been reported to infect humans [
22]. On the other hand,
Escherichia coli is found in the normal flora of the gastrointestinal tract in both animals and humans [
23]. However, it is one of the most common aetiologies in digestive pathologies and is the most frequently isolated bacterium in kidney and urogenital tract infections (UTI) in dogs and cats [
24]. Thus,
E. coli could serve as an important source of infections and resistance genes for humans [
24,
25]. However, while bacterial species can infect animals and humans in both directions, another consideration to bear in mind is that antibiotic resistance genes are spread by animals and humans through their shared environment [
23,
25].
2.3. Programmes in Development
One of the objectives of the GLG is to develop a coordinated system to control AMR and AMC surveillance and monitoring programmes [
6]. Something similar is what the EU Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections (EU-JAMRAI) aims to achieve with the EARS-Vet network in the EU Member States [
5].
To get the programme up and running, a wide-ranging review was carried out to analyse the existing programmes in the EU. The information to establish this programme was collected from 13 EU countries, 10 of which have Monitoring and Surveillance programmes for AMR, AMC or both (the Czech Republic, Denmark, Estonia, Finland, France, Germany, Ireland, the Netherlands, Norway and Sweden), and the other 3 were in the process of setting up these programmes (Belgium, Greece and Spain). The shared information about the future scope of Belgium, Greece and Spain was defined through relevant national experts [
5]. In this case, an important step was the definition of study areas, establishing which animal species/type of production/age categories/bacterial species/specimens/antimicrobials must be monitored.
Finally, EARS-Vet chose 6 animal species, i.e., cat, cattle, chicken (broiler and laying hen), dog, swine and turkey 11 bacterial species, i.e.,
E. coli, Actinobacillus pleuropneumoniae, Klebsiella pneumoniae, Pasteurella multocida, Mannheimia haemolytica, S. aureus, S. pseudintermedius, Staphylococcus hyicus, Streptococcus suis, Streptococcus uberis and
Streptococcus dysgalactiae to be monitored [
5]. Moreover, three panels of antibiotics were suggested, covering most of the combinations of importance in veterinary antimicrobial stewardship, following the EUCAST standards, recording minimum inhibitory concentration and reading antimicrobial susceptibility testing results using Epidemiological Cut-Off Values (ECOFFs) [
5].
3. Alternatives to Antibiotic Use
As reported above, AMR represents one of the greatest threats to animal, human and environment health. In the past, antibiotics have been used not only to control infections, but also to prevent pathologies and improve the health status of the animal, without limits on their use or AMR prevalence control [
36]. Therefore, high levels of AMR and multidrug-resistant bacteria are reported worldwide, so there is an ongoing quest to develop alternatives to antibiotic use in order to minimise the harm to public health [
36]. This review describes the different strategies tested and approved to reduce infections and thus minimise the occurrence of AMR in companion animals.
3.1. Probiotics
Probiotics are live microorganisms that confer benefits to host health when administered in adequate doses [
37]. There are also many microorganisms that have probiotic characteristics; the most common species to date are
Lactobacillus spp.,
Streptococcus spp.,
Lactococcus spp. and
Bifidobacterium spp. [
37,
38]. Probiotics should at least be capable of modulating the immune response or some physiological parameters of the host, treating or preventing infectious and inflammatory diseases and acting as biological preventive control agents [
36,
39].
One study evaluating the benefits of a probiotic, based on canine-derived
Bifidobacterium animalis, in dogs with acute idiopathic diarrhoea showed that the use of the probiotic combined with the improvement of nutritional management reduced the need to administer metronidazole to the diseased dogs [
37].
3.2. Prebiotics
Prebiotics are non-digestible compounds that are metabolised by gut microorganisms and modulate the composition and activity of the gut microbiota, providing benefits to the host’s physiological bacteria [
40].
According to the results reported by De Souza et al. (2019), in dogs fed a mixture of fibre and prebiotics, no negative effect on nutrient digestibility and faecal quality was observed, and increased digestibility of food was reported. In addition, beneficial changes were observed in the faeces, which may indicate support of gut health. While the test substances caused slight changes in faecal microbial populations in adult healthy dogs, they had a significant effect on faecal metabolite physiology, demonstrating a possible microbial improvement in dogs fed diets supplemented with prebiotics. However, further research is needed to establish the optimal doses according to the age of the animals and the disease stages and to understand what conditions can be prevented or treated with prebiotic supplements [
41].
3.3. Symbiotics
Symbiotics can strengthen the beneficial effects that probiotics and prebiotics have on their own, as probiotics use prebiotics as food sources to extend their survival in the digestive tract, increasing the digestibility and availability of certain nutrients such as vitamins, minerals, and proteins [
42].
A study performed in dogs with acute diarrhoea, comparing the therapeutic effect of nutraceuticals and antibiotics on clinical activity, showed that the role of symbiotics in the positive effect seen in patients is unclear. Thus, more studies are needed both in vitro and in vivo, in companion animals, to further investigate the real effect of these supplements [
43].
3.4. Postbiotics
Postbiotics are metabolites generated by the fermentation of probiotic bacteria in the gut [
37]. In the last few years, they have had a great impact, as they have also been proposed as food supplements to regulate intestinal homeostasis instead of probiotics, since they reduce the possible risks of administering living bacteria [
44]. Postbiotics are present in several species of
Bifidobacterium (
B. breve, B. lactis, B. infantis),
Bacteroides fragilis,
E. coli Nissle 1917 and
Faecalibacterium prausnitzii, among others [
45], and it has been reported that they improve the integrity of the mucosal gut barrier through different mechanisms, as well as modulate the secretion of inflammatory mediators [
44,
45].
In a study evaluating the postbiotic activities of
Lactobacilli-derived factors in vitro, postbiotics were shown to have beneficial properties in relation to pathogen-induced inflammation and altered cytokine release [
45].
However, as AMR is present in animal diseases and antibiotic treatment options sometimes do not work properly, efforts are being made to develop alternative treatments for ongoing infections [
36].
3.5. Faecal Microbiota Transplantation
Faecal microbiota transplantation (FMT) involves the transfer of faeces from a healthy donor to the intestine of a diseased recipient with the aim of adjusting the gut microbiome of the diseased subject. The gut microbiota is seriously affected by the use of antibiotics or by inflammatory gastrointestinal diseases treated with antibiotics, which further aggravates a pathology [
46].
Therefore, FMT is sometimes the only and last viable option [
46,
47]. Although more studies on FMT are needed, published clinical case reports for companion animals showed the improvement and restoration of the animal microbiota [
48]. After treatment, animals recovered appetite and body weight, and the treatment might also help restore the integrity of the intestinal barrier, along with promoting the complete disappearance of the gastrointestinal and systemic symptomatology [
46,
47].
3.6. Bacteriophage Therapy
Bacteriophages (or “phages”) are viruses that possess the natural characteristic of specifically targeting and killing bacteria [
49]. One of the advantages of phages is their ability to adapt to bacterial strains due to decades of co-evolution, which is why they are considered ‘adaptive drugs’ [
49]. Moreover, their ability to lyse different bacteria strains has been reported. Although phages are considered a promising tool as an alternative to antibiotics, in veterinary medicine studies have been focused on food-producing animals, so there are only a few in vivo studies in companion animals [
49,
50].
Although most studies have been conducted in vitro, a clinical trial was carried out to study the treatment of otitis in dogs, caused by
Pseudomonas aeruginosa, with a mixture of bacteriophages [
40]. The outcome showed that bacteriophages improved the ear condition and all the dogs remained afebrile. In addition, the treatment scope for bacteriophages is limited, as the ear microbiota should be respected, so mixtures of bacteriophages are required to cover a wide range of bacteria [
51].
All the information collected in this section is summarised in Table 1.