Combating Antimicrobial Resistance (AMR) – Increasing the Effectiveness of Antibiotics, Inventing Alternatives and Microbiome-Based Interventions

Since their introduction into clinical and veterinary medicine, antibiotics have become indispensable for treating bacterial infections, protecting animal welfare and preventing economic losses in animal production. However, their use can develop and spread antimicrobial resistance (AMR). Within the One Health framework, the spread of resistant pathogenic bacteria is a multidirectional process as resistant bacteria and resistance determinants circulate among animals, humans, food and the environment, making the preservation of existing antibiotics essential for both human and animal health.

Because the discovery and approval of new antimicrobials remains slow, several complementary strategies are needed: prudent and responsible antibiotic use, infection prevention, optimization of existing treatments and the development of safe, effective alternatives. These strategies must account for differences among target animals, including food-producing animals such as livestock, poultry and aquaculture species, as well as sport and companion animals, since species, physiology, disease and production system all influence drug exposure and response.

Optimizing antibiotic therapy requires evidence-based dosing supported by bioavailability and pharmacokinetic/pharmacodynamic (PK/PD) studies. PK/PD relationships and targets must be established for the relevant bacterial pathogen in each disease process, taking into account pathogen susceptibility, the infection site and the treated animal species. Studies may address oral, in-feed, drinking-water, intramuscular, intravenous, subcutaneous, intramammary, topical, inhalational or other clinically relevant routes, and research linking drug exposure to microbiological and clinical outcomes is particularly encouraged.

Novel formulations, including nanoformulations, may improve the stability, bioavailability, tissue distribution, targeted delivery or barrier penetration of antibiotics and alternative products. However, claimed improvements in absorption and distribution must be demonstrated through appropriate pharmacokinetic and toxicokinetic studies, and improved efficacy should be supported by PK/PD, dose-response and safety data, including residue-depletion evidence where relevant to food-producing animals. Orally administered nanomaterials should be assessed for gastrointestinal stability, absorption, effects on the gut microbiota and systemic exposure. Other routes should be evaluated according to their intended veterinary application.

Potential alternatives and complementary interventions include bacteriophages, enzymes, organic acids, probiotics, prebiotics, synbiotics, postbiotics, herbal and other natural products, and novel antimicrobial compounds. These should be characterized from ADME through to translational application. For locally acting and non-absorbed products, site-specific measures of exposure, persistence and activity may be used instead. Relevant data include composition, mechanism of action, antibacterial spectrum, effective concentration, dose-response, safety and toxicity. Efficacy should be demonstrated at practicable and safe concentrations rather than inferred from preliminary in vitro activity alone.

The effects of these alternatives on the gut microbiome also deserve attention in their own right. Unlike conventional antibiotics, which often broadly disrupt the intestinal microbial community, many alternatives may help preserve or restore microbial balance. The extent and direction of these effects depend on the product, animal species, age, diet, physiological status, and environmental and management conditions. Reported mechanisms include enrichment of beneficial taxa, greater microbial diversity and ecosystem stability, competitive exclusion of pathogens, improved gut barrier integrity, immune modulation and increased production of short-chain fatty acids (SCFAs). We especially welcome studies linking microbiome changes to animal health, performance or clinical outcomes, rather than reporting compositional shifts alone.

Studies investigating combinations are also encouraged, including antibiotics combined with any of the interventions above, or non-antibiotic combinations. Such studies should determine whether the components act synergistically, additively or antagonistically, and whether they improve efficacy, reduce the required antibiotic exposure, overcome resistance or limit adverse effects, with a clear rationale for the selected combination and dosing.

The scope of this Research Topic is to advance pharmacologically robust strategies for preventing and controlling bacterial infections while reducing unnecessary antibiotic use across food-producing, sport and companion animals, and preserving antibiotics for severe infections. Prudent antimicrobial stewardship and infection prevention, through vaccination, biosecurity, hygiene, husbandry, nutrition, surveillance and rapid diagnosis should be considered alongside therapeutic innovation.

We welcome Original Research and Review articles addressing topics including, but not limited to:

· Optimization of veterinary antibiotics through species- and pathogen-specific PK/PD studies;

· Bioavailability, pharmacokinetics, toxicokinetics and dose optimization of novel formulations, including nanoformulations, and their routes of administration;

· Bacteriophages and phage-derived antimicrobial products;

· Enzymes with antibacterial, antivirulence or antibiofilm activity;

· Organic acids and related nutritional or feed-associated interventions;

· Probiotics, prebiotics, synbiotics and postbiotics, and their effects on pathogens, host health and microbial communities;

· Herbal products and other natural products, including essential oils and flavonoids;

· Novel antimicrobial compounds and advanced delivery systems;

· ADME or site-specific disposition, mechanisms of action, antibacterial activity, safety, toxicity and residues;

· Synergistic combinations that enhance antimicrobial efficacy or help overcome resistance;

· Microbiome-based interventions and the effects of antibiotic alternatives on gastrointestinal microbial communities, microbial metabolites and the resistome;

· Modulation of microbial diversity, colonization resistance, gut barrier integrity and immune responses, and the host, dietary and management factors shaping these effects;

· Prudent antibiotic use and infection-prevention strategies across the different animal categories.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Systematic Review
• Technology and Code

Keywords: Antimicrobial resistance, Antibiotic alternatives, Nanoformulation, One Health, Phage therapy, Probiotics and synbiotics, Essential oils and flavonoids, Gut microbiota, Animal farming, Synergistic antimicrobial combinations

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.