Open Veterinary Journal, (2025), Vol. 15(2): 504-518

Review Article

10.5455/OVJ.2025.v15.i2.2

Potential of the livestock industry environment as a reservoir for spreading antimicrobial resistance

Aswin Rafif Khairullah¹, Ikechukwu Benjamin Moses², Sheila Marty Yanestria³, Fidi Nur Aini Eka Puji Dameanti⁴, Mustofa Helmi Effendi^5,6*, John Yew Huat Tang⁶, Wiwiek Tyasningsih⁷, Budiastuti Budiastuti⁸, Muhammad Khaliim Jati Kusala¹, Dea Anita Ariani Kurniasih⁹, Bantari Wisynu Kusuma Wardhani¹⁰, Syahputra Wibowo¹¹, Ilma Fauziah Ma’ruf¹⁰, Ima Fauziah¹, Riza Zainuddin Ahmad1 and Latifah Latifah¹²

¹Research Center for Veterinary Science, National Research and Innovation Agency (BRIN), Bogor, Indonesia

²Department of Applied Microbiology, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria

³Faculty of Veterinary Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia

⁴Laboratory of Veterinary Microbiology and Immunology, Faculty of Veterinary Medicine, Universitas Brawijaya, Malang, Indonesia

⁵Division of Veterinary Public Health, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

⁶School of Food Industry, Faculty of Bioresources, and Food Industry, Universiti Sultan Zainal Abidin (Besut Campus), Besut, Malaysia

⁷Division of Veterinary Microbiology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

⁸Study Program of Pharmacy Science, Faculty of Health Science, Universitas Muhammadiyah Surabaya, Surabaya, Indonesia

⁹Research Center for Public Health and Nutrition, National Research and Innovation Agency (BRIN), Bogor, Indonesia

¹⁰Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency (BRIN), Bogor, Indonesia.

¹¹Eijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Bogor, Indonesia.

¹²Research Center for Animal Husbandry, National Research and Innovation Agency (BRIN), Bogor, Indonesia

*Corresponding Author: Mustofa Helmi Effendi. Division of Veterinary Public Health, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia. Email: mhelmieffendi [at] gmail.com

Submitted: 21/10/2024 Accepted: 02/01/2025 Published: 28/02/2025

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Abstract

Antimicrobial resistance (AMR) in bacteria is a global issue requiring serious attention and management. The indiscriminate use of antibiotics in livestock for growth promotion, disease prevention, and treatment has led to the dissemination of AMR bacteria and resistance genes into the environment. In addition, unethical antibiotic sales without prescriptions, poor sanitation, and improper disposal cause significant amounts of antibiotics used in livestock to enter the environment, causing the emergence of resistant bacteria. Intensive livestock farming is an important source of AMR genes, environmental bacteria contamination, and possible transfer to human pathogens. Bacteria intrinsically antibiotic resistant, which are independent of antibiotic use, further complicate AMR and increase the risk of morbidity and mortality following infections by AMR bacteria. Escherichia coli, Salmonella spp., and Staphylococcus spp. are commonly found in livestock that carry resistance genes and have a risk of human infection. The impact of AMR, if left unchecked, could lead to substantial public health burdens globally, with a predicted mortality rate higher than cancer by 2050. “One Health” integrates strategies across human, animal, and environmental health domains, including improving antibiotic stewardship in livestock, preventing infection, and raising awareness regarding the judicious use of antibiotics. The use of antibiotic alternatives, such as prebiotics, probiotics, bacteriophages, bacteriocins, and vaccinations, to control or prevent infections in livestock will help to avoid over-reliance on antibiotics. Coordinated international actions are needed to mitigate the spread of AMR through improved regulations, technology improvements, and awareness campaigns.

Keywords: AMR, Antibiotic, Environment, Livestock, Public health.

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Introduction

Ecosystems supporting livestock are crucial sites for the dissemination of antibiotic resistance (Widodo et al., 2022; Ansharieta et al., 2021). The capacity of bacteria to grow and survive in the presence of concentrations of antibacterial drugs that are usually sufficient to either kill or restrict their growth is known as antimicrobial resistance (AMR) (Salam et al., 2023). Additionally, it describes a bacteria’s capacity to fend against the effects of one or more drugs [also known as multidrug resistance (MDR)] (Tyasningsih et al., 2022). Antibiotic pollution in the environment is primarily caused by waste from livestock activities (Kraemer et al., 2019). A significant selection for resistant microbes occurs as a result of up to 90% of antibiotics used in cattle production, which eventually find their way into the environment (Polianciuc et al., 2020). The overuse and improper use of antibiotics over an extended period of time invariably results in the development of bacterial resistance (Khairullah et al., 2020).

AMR has become a global concern for people, animals, and the environment in the twenty-first century (Tang et al., 2023). The primary factor contributing to the global spread of AMR is the overuse of antibiotics in the veterinary, medicinal, and agricultural fields (Pradika et al., 2019; Effendi et al., 2018). The problem has been exacerbated by the unethical sale of antibiotics without prescription, inadequate sanitation standards, and the discharge of antibiotic residues or unmetabolized drugs into the environment through industrial waste, manure, and excrement (Serwecińska, 2020). The elements that contribute to the environmental spread of antibiotic resistance are significantly correlated. In the absence of comprehensive action plans, the yearly death toll is predicted to surpass cancer mortality by 2050, with 10 million deaths annually (de Kraker et al., 2016).

The degree of antibiotic consumption, which is determined and controlled by a nation’s antibiotic policy, determines the patterns of antibiotic resistance in different areas and nations. Nevertheless, China is recognized as the world’s top manufacturer and user of antibiotics for both humans and animals (Xu et al., 2020). The emergence of AMR in animal products and waste, the abuse of antibiotics that leads to their eventual escape into the environment, and the absence of rigorous and efficient oversight and control over the manufacture, use, and disposal of antibiotics are the main causes of the antibiotic crisis (Muteeb et al., 2023). The emergence and dissemination of antibiotic-resistant genes in food and the environment, together with the abundance of these bacteria, have all been greatly exacerbated by human activities in reaction to industrialization (Manyi-Loh et al., 2018). This also increased the overall abundance of both bacteria and resistance genes.

The use of antibiotics in cattle and poultry has recently gained international attention, and it is predicted that by 2050, the percentage of these animals that use antibiotics will reach 67% in developing nations (Rahman et al., 2022). The cost of providing health care worldwide has increased dramatically as a result of the growing AMR issue of a worldwide scale. Although quantifying the global costs of antibiotic resistance is challenging, AMR carries a hefty financial cost (Poudel et al., 2023). The World Health Organization (WHO) has been more interested in funding research to create new antimicrobial compounds against priority pathogens because of the growing resistance of bacteria to antibiotics as a last option (WHO, 2017).

Given the lengthy history of antibiotic use in livestock, the establishment of AMR was unavoidable. However, the general public is becoming more aware of sensible measures to reduce unnecessary and overuse of antibiotics. A “One Health” strategy must be used to address AMR because of the interdependence of human, environmental, and animal health (Cella et al., 2023). Understanding how the livestock business environment might serve as a reservoir for the emergence of antibiotic resistance is a crucial topic covered in this article. This review provides fresh perspectives on how to address issues related to AMR in livestock environments.

AMR as a global problem

AMR, a global problem, is mostly caused by antibiotics and genes that confer resistance to antibiotics. However, other factors such as pollution and poor local sanitation also contribute to AMR (Graham et al., 2019). The main causes of antibiotic resistance are incorrect and insufficient use of antibiotics, ignorance leading to overuse or inappropriate use of antibiotics, poor sanitation and hygiene, excrement releasing unmetabolized antibiotics or their residues into the environment, and the use of antibiotics in poultry and livestock as growth promoters rather than infection control agents (Prestinaci et al., 2015). These factors facilitate the genetic selection pressure that influences the formation of MDR bacterial diseases in the community. The primary pathogens in this category are Salmonella spp., Staphylococcus spp., Escherichia coli, and Campylobacter spp. (Almansour et al., 2023). Furthermore, bacteria from humans or animals have been shown to exhibit similar resistance mechanisms.

In the study of resistant microbes, it is crucial to address the molecular evolution of resistance within a given organism, the mechanisms and pathways of transmission between organisms, the spread of resistant microbes between human and animal hosts, and the larger environment, including soil and water (Cycoń et al., 2019). Approximately 80% of the commercially available antibiotics are used as growth promoters or to treat infections in animals (Hosain et al., 2021). The 2010 estimate of livestock antibiotic use on the world antibiotic map was 63,151 tons (Van Boeckel et al., 2015). This predicament has the potential to cost the world economy $120 trillion ($3 trillion annually), or almost the same as the whole yearly budget that the United States currently spends on health care (Aslam et al., 2018). Antibiotic usage patterns will result in 444 million deaths by the year 2100 and a sharp decline in birth rates by the year 2050 (Tang et al., 2023).

Use of antibiotics in livestock farming

For many years, antibiotics have been used in agriculture for growth promotion, prevention, and therapeutic purposes (Van et al., 2020). Presently, the pig, chicken, and cow industries use thousands of tons of antibiotics every year. The most widely used medications include penicillin, chlortetracycline, oxytetracycline, phospholipid flavoring, and bacitracin, according to reports from European countries (EFSA et al., 2021). Many studies have shown that broad-spectrum antibiotics, as listed in Table 1, such as sulfamethazine (Awaisheh et al., 2019), tylosin (Murray et al., 2022), netilmicin (Dimitrova et al., 2022), lincomycin (Wijayanti et al., 2024), chloramphenicol (Widodo et al., 2023), ciprofloxacin (Dameanti et al., 2023), sulfamethoxazole (Stastny et al., 2023), chlortetracycline (Yu et al., 2022), tetracycline (Khairullah et al., 2023a), doxycycline (Castro et al., 2009), florfenicol (Bardhi et al., 2023), oxytetracycline (Yanestria et al., 2024), sulfadiazine (Hahne et al., 2023), enrofloxacin (Guo et al., 2023), norfloxacin (Al-Mustafa and Al-Ghamdi, 2000), erythromycin (Khairullah et al., 2024a), monensin (Arikan et al., 2018), and trimethoprim (Jang et al., 2015) are found in livestock ecosystems across several continents. Genes indicating resistance to tetracycline and macrolide antibiotics are the most commonly identified because of the lengthy history of usage of these antibiotic families in cattle husbandry (Zhuang et al., 2021).

Antibiotics are used prophylactically (e.g., to prevent the spread of an infection that is present in a specific area) and therapeutically (e.g., administering antibiotics to the entire herd as a metaphylactic treatment to treat sick animals and prevent the spread of disease) (Rahman et al., 2022). The age and breeding stage of the animal determine the type and quantity of antibiotics used; for example, antibiotics are typically administered during breastfeeding and after weaning. In Belgium, preventive measures account for approximately 90% of the total antibiotic use in pig production (Postma et al., 2016).

Antibiotics are currently prohibited from being used as growth promoters in many nations, and attempts are being made to restrict their usage in preventive medicine (Kongsted and Mc Loughlin, 2023). Therefore, the general quantitative consumption levels of these medications were not considerably affected by the prohibition against the use of antibiotics as growth promoters. Antibiotics used in animal agriculture are significantly more common than those used in human medicine. For instance, the Netherlands uses approximately 100 tons of antibiotics annually for the treatment of animals (Mevius and Heederik, 2014). Cross-resistance may develop because many antibiotics used in animal husbandry share structural similarities with those used in human medicine (Wibisono et al., 2022).

Livestock as AMR reservoir

One of the reasons for the environmental spread of antibiotic resistance is intensive livestock production (Karwowska, 2024). Livestock facilities are seen as hotspots for antibiotic resistance, and livestock itself is thought to be a significant reservoir of genes and microorganisms resistant to antibiotics (Yanestria et al., 2022). Bacteria with heightened antibiotic resistance can also be found in livestock (Wibisono et al., 2021). Animal isolates may be more likely than human strains to have multiresistant Escherichia coli strains and to be resistant to extended-spectrum β-lactam antibiotics (Xiao et al., 2024). Farm animals are often brought up on cattle and goat farms where antibiotics and their phage are in plentiful supply (Fig. 1). Irrationally excessive antibiotic administration in animal husbandry leads to the acquisition of resistant strains of bacteria (Khairullah et al., 2024b). These resistant bacteria or their genetic material may be disseminated into the environment via several pathways. These pathways include waste materials from farming animals, watersheds, stormwater, and the discharge of antibiotics and resistant bacteria during industrial activity (Kunhikannan et al., 2021). Resistant strains are further distributed to urban and agricultural areas via dirty water (Reddy et al., 2022). This phenomenon perpetuates the cycle of advanced microbial-resistant strains in ecosystems. Urbanization, agricultural development, and industrialization are important factors in the progression of AMR (Mshana et al., 2021).

Zhu et al. (2013) found that three large-scale industrial pig farms in China that use antibiotics for farming have 149 distinct genes that cause antibiotic resistance. According to Effendi et al. (2022), the gene blaCTX-M-1 encodes an extended spectrum β-lactamase (ESBL) that is frequently expressed in livestock. It has been discovered that tetracycline resistance genes are present in pig farm animals as well as in the soil or water (Monger et al., 2021). Lau et al. (2017) reported up to 34 novel antibiotic resistance genes in soil samples contaminated with antibiotics used in animal production, such as chlortetracycline, sulfamethazine, and tylosin.

The relationship between drug resistance and the use of antibiotics in cattle husbandry is not fully understood. On the one hand, there is no question that the use of antibiotics and the existence of bacteria resistant to the drugs, as well as genes that determine antibiotic resistance, are related (Muteeb et al., 2023). According to studies by Caneschi et al. (2023), using antibiotics in pig production can cause a three- to four-fold increase in the frequency of drug resistance genes. On the other hand, Khairullah et al. (2023b) reported data supporting the presence of antibiotic resistance in pig farms without antibiotic use, suggesting that antibiotic resistance is a naturally occurring source of antibiotic resistance. An unexpected discovery was made by Salerno et al. (2022) that the antibiotic resistance genes blaTEM, sul2, qnrS, and tetA were detected in broiler farms that did not use antibiotics. Their relative abundance was determined to be similar to that of industrial farms as a whole. In addition, studies conducted on chicken farms by Liu et al. (2020a) showed that antibiotic resistance genes were present in broiler farms that used antibiotics as well as those that did not.

Table 1. Antibiotic use in livestock farming.

Fig. 1. Pathways of AMR transmission from livestock to the environment.

There is evidence to suggest that certain bacteria in the digestive tracts of animals may naturally withstand antibiotics, independent of the stress brought on by antibiotic use (Kim et al., 2017). Through selection in the presence of antibiotics provided to feed or through contact with drug-resistant microflora in the surrounding environment, such as during grazing, antibiotic-resistant bacteria can colonize livestock species (Xu et al., 2022). This suggests that limiting the use of antibiotics in cattle ranching alone may not be sufficient to curb the spread of drug resistance in livestock. Nonetheless, a correlation has been noted between the antibiotic resistance profile of the bacteria and the makeup and organization of the intestinal microflora in pigs, chickens, and cattle (Wickramasuriya et al., 2022).

Antibiotic use as a preventive measure is justified by the fact that intensive farming involves the concentration of a high number of people in a comparatively small area, increasing the risk of infectious disease transmission (Rahman et al., 2022). This is crucial, particularly for large-scale poultry breeding. Concurrently, an Ecuadorian study verified that industrially raised chickens exhibit a higher prevalence of bacterial antibiotic resistance than domestically raised birds (resistance to tetracycline, 78% and 34%, respectively, to sulfisoxazole, 69% and 20%, and to trimethoprim/sulfamethoxazole, 63% and 17%, respectively) (Braykov et al., 2016). Furthermore, it is suggested that the size of the herd, the degree of interpersonal contact, the availability of open areas and pens, and feeding practices all play a role in the development and dissemination of antibiotic resistance in pigs (Redman-White et al., 2023). Österberg et al. (2016) evaluated the prevalence of antibiotic-resistant E. coli bacteria in the digestive tracts of slaughtered pigs from conventional and organic farms in Denmark, Sweden, France, and Italy. The authors discovered that tetracycline, ampicillin, streptomycin, sulfonamides, trimethoprim, ciprofloxacin, nalidixic acid, and gentamicin caused far less antibiotic resistance when farming organically (Iwu et al., 2020).

AMR transmission in livestock

Livestock excrement contains some of the antibiotics used in livestock production. The body’s ability to metabolize antibiotics varies greatly, from 10% to 90% of the amount taken; this variability is probably influenced by the animal’s age and species (Manyi-Loh et al., 2018). Antibiotics themselves as well as their metabolic byproducts are thus present in the feces. According to a study, animal production solid waste included roughly 12 mg/kg of doxycycline and 241 mg/kg of ciprofloxacin. The antibiotic values for liquid waste were 0.006 and 0.505 mg/l, respectively (Haenni et al., 2022). By comparing these values with concentrations of antibiotics suspected of inducing resistance selection (0.064 µg/l for ciprofloxacin and 2 µg/l for doxycycline), it can be argued that this waste actually threatens the resident microflora’s ability to resist antibiotics (Bengtsson-Palme and Larsson, 2016).

Bacteria isolated from animal excrement exhibit antibiotic resistance (Galler et al., 2021). Drug-resistant bacteria are more prevalent in animal feces and the intestinal microflora when antibiotics are administered to feed for therapeutic or prophylactic purposes (Putri et al., 2023). Therefore, it is common to identify agents responsible for antibiotic resistance in animal feces.

According to Lima et al. (2020), a number of factors affect the potential role of manure as a hotspot for horizontal gene transfer of traits related to antibiotic resistance, including the abundance of nutrients, the presence of antibiotic residues that may act as selection factors, and the diversity and quantity of microorganisms. Antibiotic resistance genes can be up to 10% more prevalent in manure than 16S rRNA genes. Livestock manure has been found to include a variety of harmful bacteria, including Klebsiella pneumoniae and bacteria with antibiotic resistance traits from the genera Listeria, Salmonella, Coxiella, Campylobacter, and Mycobacterium. The use of manure from livestock farms that have administered antibiotics to their animals as fertilizer is one of the primary drivers of drug resistance in the soil environment (Tian et al., 2021). Research has verified that soil treated with manure contains genes that are resistant to tetracycline, fluoroquinolone, sulfonamide, and chloramphenicol (Wang et al., 2023).

In an investigation of antibiotic resistance on Finnish pig and cattle farms, Ruuskanen et al. (2016) discovered that manured soil had high concentrations of resistance genes to tetracyclines (tetM), sulfonamides (sul1), and carbapenems (blaOXA-58), even in situations where animal husbandry typically used very small amounts of antibiotics. It has been noted that germs resistant to antibiotics can endure in the environment for a considerable amount of time. The soil type, composition, frequency of fertilization, and type of microflora are all conditioning factors (Rad et al., 2022). The possibility of additional environmental transmission of antibiotic resistance is another factor. One fascinating phenomenon that may indicate the environmental dissemination of these genes is the discovery of additional antibiotic resistance genes in soil following manure fertilization (Han et al., 2022). Antibiotic resistance in soil microorganisms may be further promoted by antibiotics present in manure (Huygens et al., 2021). The study conducted by Kousar et al. (2021) evaluated the prevalence of antibiotic resistance in Pseudomonas aeruginosa strains isolated from the topsoil of poultry farms where antibiotics were used to grow birds and bacteria of this species from regions at least 500 meters from the closest poultry farm. The samples obtained from both sites showed signs of antibiotic resistance. Fascinatingly, strains of E. coli resistant to florfenicol were identified from farms that were geographically separated.

There is evidence that the periodic rise in antibiotic resistance-granting genes in soil environments is caused by manure fertilization (Lima et al., 2020). Additionally, resistance genes might gradually become less common in soil environments. A study by Muurinen et al. (2017) on pig and dairy farms in Finland revealed that although some resistance genes were present in manure, the amount of these genes steadily decreased in soil treated with manure. Baker et al. (2022) found a strikingly similar result for stored manure: a gradual decline in antibiotic-resistant bacteria. It should be noted, nevertheless, that 163 genes related to antibiotic resistance were also found in unfertilized soil, whereas 230–245 genes were found in manured soil, depending on the type of animal.

It should be mentioned that using composting is a strategy to lessen the spread of antibiotic resistance caused by the use of natural fertilizers. Antibiotic residues can be removed from samples by up to 50%–99% through manure composting; the greatest results are achieved at higher temperatures and longer thermophilic phases (Li et al., 2020). Regretfully, under composting conditions, certain antibiotics, such as ciprofloxacin, ofloxacin, and sulfamethazine, might not break down while their concentrations in the finished product are still high (Narciso et al., 2023). There is evidence to support the claim that composting manure can effectively reduce the levels of resistance-conditioning genes and bacteria resistant to antibiotics (Huang et al., 2021; Qiu et al., 2021).

Composting pig manure at the right temperature and pH can potentially slow the propagation of genes that cause antibiotic resistance, as shown by Liu et al. (2020b). Nevertheless, it was discovered that conventional composting methods were ineffective in managing antibiotic resistance. During the thermophilic phase, even raising the temperature causes a cyclical decrease in the number of resistance-determining genes. Furthermore, our findings suggest that the amount of antibiotic resistance in the composted material may decrease, stabilize, or even grow during composting. Wang et al. (2021) found a nine-fold increase in the number of antibiotic resistance genes (namely, sul1, sul2, tetQ, and tetX genes) in aerobic pile composting of sheep manure.

Wang et al. (2022a) reported that the frequency of antibiotic resistance genes increased 44-fold during pile composting, with macrolide antibiotic resistance being the most common type. On the other hand, during composting under thermophilic conditions, tetracycline resistance genes increased to 97%, leading to a 92% decrease in antibiotic resistance genes. Tetracycline resistance gene abundance varies depending on the activity of microflora and environmental conditions (pH, moisture content, and C/N ratio) during composting. The survival of antibiotic-resistant bacteria in manure and compost, as well as the retention of antibiotic resistance genes in microbial communities, may be affected by the presence of heavy metals and drug residues (Shen et al., 2023).

Impact of AMR on public health

The worldwide health care system is financially impacted by the careless discharge of antibiotics into the environment (Polianciuc et al., 2020). The European Center for Disease Control (ECDC, 2018) estimates that 25,000 people die each year from antibiotic-resistant bacterial infections, which affect roughly 2 million Americans annually. The characteristics of AMR include recurrent infections, treatment delays, and resistance spreading to other species (Huemer et al., 2020). Multidrug-resistant health care infections and AMR have given rise to a range of clinical issues. According to the Centers for Disease Control (CDC) estimates, hospitalized patients in the United States have approximately 32,600 cases of MDR Pseudomonas aeruginosa, 197,400 cases of ESBL-producing Enterobacteriaceae, and 223,900 cases of Clostridium difficile annually (CDC, 2019). Given the current situation, more attention should be given to the widespread use of antibiotics and the evaluation of the risks associated with antibiotic residues on human health. Four primary domains, including risk characterization, exposure assessment, hazard identification, and dose–response relationships, should be included in the evaluation of antibiotic-resistant bacterial risks (Murray et al., 2020). Human antibiotic resistance is believed to be caused by changes in the human microbiome caused by antibiotic residues in the environment, which lead to the appearance and selection of resistant bacteria in the human gut (Muteeb et al., 2023). Environmental antibiotic resistance can occasionally result from selective pressure on the environmental microbiome, which serves as a reservoir of antibiotic-resistant bacteria and antimicrobial resistance genes (ARGs) (Larsson and Flach, 2022).

In addition to true pathogens such as Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Campylobacter jejuni, and Salmonella spp., Gram-negative pathogens that cause nosocomial infections include Pseudomonas aeruginosa, Clostridium difficile, Burkholderia cepacia, and Acinetobacter baumannii (Davies and Davies, 2010). This infection causes a number of illnesses in humans and animals. According to estimates from the US CDC and Prevention, antibiotic-resistant illnesses claim the lives of 23,000 Americans annually (Thorpe et al., 2018). The first-line antibiotics cannot treat many common diseases, and the germs that cause these infections can also be found in cattle. It is a difficult task to investigate the connections between hazards to human health and the use of antibiotics in livestock husbandry (Bava et al., 2024). There is no straightforward model that explains how resistant microorganisms evolve for epidemiological reasons in terms of the dynamics of antibiotic resistance. It is unknown how much each type of antibiotic contributes to the overall problem of antibiotic resistance.

One health approach to AMR management

Microorganisms are omnipresent and encompass a range of AMR properties in all ecological contexts. AMR between humans, animals, and the environment is becoming more widespread because of the intricate web of interactions that take place between microbial specimens from various “environments,” which promotes gene flow (Palma et al., 2020). This creates a multifaceted issue. Thus, it is preferable to investigate and handle this warning phenomenon using a coordinated multisectoral strategy such as One Health (Velazquez-Meza et al., 2022). To achieve the best possible health for humans, animals, plants, and the environment, One Health is described as “a collaborative effort of multiple health science professions, along with related disciplines and institutions—working locally, nationally, and globally.” (Nzietchueng et al., 2023). According to such a thorough analysis, the primary causes of AMR are the use of antibiotics in the human, animal, and environmental sectors, as well as the global-scale resistance mechanisms that are spreading within and between these sectors (Salam et al., 2023).

Because the veterinary and human health care industries share the majority of the same class of drugs, bacteria are subject to cumulative selective pressure, which lowers the effectiveness of antimicrobial-based treatments in the human, veterinary, and environmental domains (Majumder et al., 2020). Increasing awareness when prescribing antibiotic therapy, preventing overprescription, and enhancing hygienic conditions and infection control programs are some of the major steps that the One Health approach has made in the human sector (Muteeb et al., 2023). To lessen the general transmission of AMR features across sectors, One Health initiatives related to the environmental sector include proper handling of industrial, civic, and livestock waste (Chua et al., 2021). Given the complexity and breadth of the One Health approach, the livestock industry should focus on actions fueled by this strategy. In addition to the necessity for international regulations restricting the use of antibiotics as growth promoters in various animal-producing nations, this involves assessing the effects of domestic animal populations and human–animal relationships, the environmental effects of aquaculture, the effectiveness of human and animal treatments, and the reduction of the mass treatment of animal herds (Caneschi et al., 2023).

Alternatives to antibiotics

The range of effective substitutes for antibiotics in livestock is largely comparable to that in human medicine. Today, prebiotics and probiotics are widely available; nevertheless, their efficacy is unknown and may vary. It has also been proposed to combine the two, which are referred to as “synbiotics.” The use of bacteriophages and bacteriocins is another alternative (Batista et al., 2020). Bacteriophages exploit bacterial cells for their replication (Secor and Dandekar, 2020). Treatment for Salmonella typhimurium in pigs and poultry has been demonstrated to be beneficial with phage therapy; however, this approach necessitates quick phage delivery and selection (Abd-El Wahab et al., 2023). Two commercial Listeria phage products, Listex P100 and ListeShield, have been approved for use as food preservatives (Kawacka et al., 2020). Numerous studies have investigated how well this new product works against Listeria monocytogenes. For instance, Soni and Nannapaneni (2010) observed a 5-log reduction in L monocytogenes following 24-h, room temperature treatment with Listex P100. Additionally, this substance was tested against developed biofilms of L monocytogenes. Following a 24-h application of Listex P100 at 20°C, Iacumin et al. (2016) observed total disintegration of the biofilm of Listeria monocytogenes on stainless steel wafers. Other authors reported only a 2-log reduction in Listeria during a 2-h treatment period (Sadekuzzaman et al., 2017).

One potential antibiotic substitute is the use of bacteriocins, which are antibacterial proteins or peptides generated by ribosomes (Yang et al., 2014). Bacteriocins have attracted considerable interest in the field of antimicrobial research during the past 10 years because of their unique mode of action. These antimicrobial peptides or proteins may have bacteriostatic (i.e., halting cell growth) or bactericidal (i.e., inducing cell death) effects, depending on the type of bacteriocin (Simons et al., 2020). To prevent the synthesis of peptidoglycans, several bacteriocins specifically target lipid II, an integrative molecule found in bacterial cell membranes (Malin and de Leeuw, 2019). Another type of bacteriocin with a binding affinity for lipid II causes the formation of a pore in the bacterial cell membrane. This leads to a reduction in turgor, disruption of electrochemical gradients, and, eventually, cellular demise (Pérez-Ramos et al., 2021).

In addition to targeting the bacterial cell wall envelope, several classes of bacteriocins can disrupt essential metabolic processes such as protein synthesis, DNA replication, and gene expression (Darbandi et al., 2020). Lactic acid bacteria (LAB) are the most well-known bacteria that produce bacteriocins, whereas many other species of bacteria can also produce these antimicrobial peptides. Gómez et al. (2016) evaluated the biofilms of three LAB species (Lactococcus lactis, Lactobacillus curvatus, and Lactobacillus sakei) against significant foodborne pathogens, namely L. monocytogenes, E. coli, and Salmonella typhimurium serovar enterica. A different research team by Minei et al. (2008) found a 3.5 log reduction in the attack of L. monocytogenes biofilms within 48 hours after using nisin, a bacteriocin licensed for commercial use, for 9 hours. The variation in bacteriocin is rather high. Alverz-Sieiro et al. (2016) reported that LAB can create over 230 distinct bacteriocins. To some extent, this intriguing antimicrobial peptide has been studied. Nevertheless, none of the aforementioned solutions has widespread commercial availability to treat the entire spectrum of microbial illnesses affecting livestock.

Currently, expanding the alternatives for animal immunization might be a more practical strategy. Although vaccines exist for many of the major viral diseases affecting cattle, they are not now routinely used to prevent bacterial infections and diseases (Choudhury et al., 2021). Although the vaccine is not widely used, a trial on live oral Lawsonia inoculation in pigs revealed an 80% reduction in oxytetracycline consumption and enhanced productivity (Bak and Rathkjen, 2009). A long-term plan to reduce antibiotic use in livestock might involve the use of genetically modified animals that are resistant to disease (Mann et al., 2021). An early success in this field is the development of transgenic hens that are unable to spread avian influenza (Lyall et al., 2011). Apart from the previously discussed strategies, there has been positive success in using combinations of molecules to take advantage of the weaknesses of bacteria that would not otherwise respond well to antibiotics. According to Harrison et al. (2019), penicillin can be effective against a considerable proportion of MRSA isolates, including those belonging to the USA300 lineage, when treated with clavulanic acid, a β-lactamase inhibitor.

AMR control mitigation

Numerous European nations have implemented measures to mitigate the occurrence and dissemination of antibiotic resistance through the prudent administration of antimicrobial medications (Shelke et al., 2023). The US Food and Drug Administration has unveiled a strategy to monitor AMR. AMR has been successfully addressed by nations that have created integrated national programs. The prudent use of antibiotics, the “One Health Approach” for monitoring antibiotics, improvements in health care systems, the creation of health insurance policies, the restriction of medication advertising, well-thought-out disease control guidelines, and community management plans are important variables (Rahman et al., 2022). These tactics also call for a great deal of endurance, time for planning, and adequate government funding. Antibiotic resistance is actively controlled by international organizations such as the Food and Agriculture Organization, the Centers for Disease Control and Prevention, Office International des Epizooties, and the WHO Global AMR Surveillance System. The Global Health Security Agenda (GHSA) and the AMR Action Package (GHSA Prevent-1 Action Package) are two additional initiatives aimed at tackling the worldwide threat of antibiotic resistance.

Another pressing issue is diagnostics, particularly in underdeveloped nations where the identification of bacteria is still performed using antiquated microbiology equipment (Wang et al., 2022b). Personalized treatment based on updated and enhanced molecular diagnostic techniques for the necessary antibiotic therapy can close this gap. Research on the interactions between humans and animals and the creation of novel screening instruments can be greatly aided by the One Health approach (Velazquez-Meza et al., 2022). The mechanisms of AMR transmission among all constituents (human, animal, and environment) of a single health system have been uncovered, making this topic extremely relevant and worthy of serious consideration. One of the main causes of AMR, particularly in low- and middle-income countries (LMIC), is the careless and inappropriate use of antibiotics (Otaigbe and Elikwu, 2023). Antibiotics are overprescribed for a number of reasons, including inaccurate diagnoses, especially in poor nations, patient satisfaction with the physician’s prescription, and the bothersome challenges that pharmaceutical businesses face (Thakolkaran et al., 2017). There is an urgent need for advancement in combination therapy, technical innovation, and antibiotic development because the absence of new antibiotics may make it more difficult to investigate this issue (Gupta et al., 2022). AMR and its effects on human and animal health, the role of various factors in its development, the impact of anthropogenic inputs from organizations, and, most importantly, technological, social, and financial initiatives for reducing environmental AMR should be the main areas of focus for future research.

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Conclusion

There is growing concern about AMR bacteria originating from the livestock industry, which poses a significant threat to humans, animals, and the environment. The livestock industry has become a major reservoir of AMR bacteria and resistance genes due to the indiscriminate use of antibiotics. Resistant pathogens can be transferred to humans through food, water, or direct contact. “One Health” approach highlights the importance of the interconnectedness of human, animal, and environmental health to address AMR. Improved antibiotic stewardship and reduced antibiotic usage in livestock while employing alternatives to promote the growth of good bacteria, such as prebiotics and probiotics, to control pathogen colonization. AMR problems can only be successfully managed through coordinated international action, technology advancement, improved public awareness, and continuous research. Without significant strategies and action to control AMR bacteria, there will be serious consequences in years to come, such as ineffective medical treatment for simple infections.

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Acknowledgments

The authors would like to thank Universitas Airlangga.

Conflict of interest

The authors declare no conflict of interest.

Funding

This study was partly supported by the International Research Consortium, Lembaga Penelitian dan Pengabdian Masyarakat, Universitas Airlangga, Surabaya, Indonesia, in 2024 (grant number: 171/UN3.LPPM/PT.01.03/2024).

Author’s contributions

ARK, BWKW, SMY, and SW drafted the manuscript. LL, FNAEPD, MHE, and IBM revised and edited the manuscript. JYHT, DAAK, WT, and IFM participated in preparing and critical checking this manuscript. IF, RZA, BB, and MKJK edited the references. All authors have read and approved the final manuscript.

Data availability

All references are open-access, so data can be obtained from the online literature.

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