Antimicrobial Resistance: The Impact from and on Society According to One Health Approach

Abstract

Antibiotics are drugs that target and destroy bacteria, and they are hailed as one of the most amazing medical breakthroughs of the 20th century. They have completely changed how we treat infections and have saved countless lives. But their usefulness is not limited to just medicine; they have also been used for many years in sectors like farming to prevent infections in animals, especially in less wealthy countries. Antimicrobial resistance (AMR) is the ability of microorganisms such as bacteria, viruses, fungi, and parasites to resist the effects of antimicrobial agents, like antibiotics, antivirals, antifungals, and antiparasitics, that were once effective in treating infections caused by these organisms. AMR presents an intricate challenge that endangers the health of both humans and animals, as well as the global economy, and the security of nations and the world at large. Because resistant bacteria are swiftly appearing and spreading among humans, animals, and the environment worldwide, AMR is acknowledged as a challenge within the framework of One Health. The One Health approach involves cooperation among various fields to attain the best possible health outcomes for humans, animals, and the environment. It acknowledges the interconnectedness of human, animal, and environmental health. AMR is not merely a scientific or medical issue; it is a societal challenge that demands collective action and awareness. In the intricate tapestry of society, every thread contributes to the fabric of AMR, and every individual holds a stake in its resolution.

1. Introduction

The discovery of antibiotics and their clinical use represented a breakthrough in 20th-century medicine, as it allowed the treatment of various infectious diseases and facilitated the execution of numerous medical techniques and procedures [1]. For several years, antibiotics were successfully employed, significantly reducing the morbidity and mortality associated with infectious diseases [2]. However, over the years, factors such as improper and excessive antibiotic use, the utilization of antibiotics as growth promoters in animal production, pharmaceutical industry pollution, lack of sanitation, and the increase in regional and international travel have led to a decrease in antimicrobial efficiency, thereby promoting bacterial resistance [3].

Since the commercialization of penicillin in 1940, antibiotics have been used in human and veterinary medicine, contributing to improving health and prolonging life expectancy. Over the years, antibiotics have been used in animals not only to treat, control, and prevent infections but also to promote growth in livestock [4]. Antimicrobial growth promoters have been used in livestock farming in the United States (US) and other developed countries for at least 50 years. The European Union banned the use of all antibiotics in feed as growth promoters in 2006 [5]; however, this restriction has not prevented the continuous increase in antibiotic resistance, and it is estimated that between 2010 and 2030, global antibiotic consumption in cattle, poultry, and pigs will increase by 67% [6,7]. Between 2012 and 2021, there was a continued increase in the use of broad-spectrum antibiotics in hospitals. The administration of these antibiotics increased by 15% over the past few years; the administration of carbapenems increased by about 34%, and the proportion of antibiotic used as a last resort for treating infections caused by multidrug-resistant bacteria doubled [8].

The misuse and overuse of antibiotics have led to the adaptation of microorganisms, resulting in antimicrobial resistance (AMR), where microbes evolve to resist treatments that once inhibited them [9]. This makes infections harder to treat and more dangerous. AMR is driven by genetic mutations, particularly in bacteria, due to widespread antibiotic use, which is a major issue globally, especially in developing countries [9]. The rise of resistant infections is now a critical public health threat, affecting health and food security worldwide. Addressing AMR is complex, involving factors across healthcare, agriculture, and global trade, making it one of the most challenging public health issues today [10].

Antibiotic susceptibility loss by bacteria can occur due not only to their excessive use and misuse, but also antibiotic use in the agricultural industry, low availability of new antibiotics, international travel, poor hygiene conditions that enhance bacterial proliferation and horizontal gene transfer mechanisms among them, and the release of unprocessed antibiotic metabolites by the body into the surrounding environment [11]. All these factors enhance the appearance of multidrug-resistant bacteria giving rise to an increasingly serious concern for public and global health, according to the World Health Organization (WHO), and for the environment and its interactions overall, considering a One Health perspective [12].

Over the past seventy-five years, concerns about antibiotic resistance have been shaped by interconnected factors, including the evolution and spread of resistant microorganisms; detection efforts; changing models and projections of resistance’s impact on future medical, social, and economic contexts; and the relationship between antibiotic use and medical and veterinary practices. Additionally, the global context of resistance, coordination of efforts, and development of infrastructure and funding to raise awareness and address antimicrobial resistance have all influenced the response to this issue [13]. Thus, epidemiological surveillance studies are essential for assessing the impact of antibiotic resistance, and infection control, and providing information on emergence and occurrence [13].

AMR represents an ecological issue marked by intricate interactions among various microbial communities, impacting the health of humans, animals, and the environment [14]. Currently, antibiotic resistance is a concern in global public health and a significant threat to healthcare systems not only in developing countries but worldwide [15]. The fact that antibiotics cannot treat common infectious diseases leads us to a state of uncertainty about the future of human, animal, and environmental health [16]. In the case of human health, infections caused by multidrug-resistant bacteria lead to the development of serious diseases, secondary and widespread infections, prolonged hospitalizations, increases in healthcare costs, and treatment failures, which can also lead to the consequent death of the individual [17]. Currently, the impact of antibiotic resistance in Europe is comparable to the impact of influenza, tuberculosis, and HIV combined [8]. It is estimated that over 35,000 individuals die every year in the European Union and European Economic Area countries due to infections caused by antibiotic-resistant bacteria. This figure adds up to over 874,000 disability-adjusted life years due to infections, both in hospital and community settings, representing over EUR 1.5 billion in direct and indirect costs [18].

Although the prevalence of antibiotic resistance in animals is not as well quantified as in humans, it is known that companion animals, livestock, and even wildlife are reservoirs of multidrug-resistant strains [19,20]. The resistance to antimicrobials in livestock animals greatly affects their health and can lead to infections caused by resistant bacteria in humans. Additionally, it diminishes the effectiveness of antimicrobial treatments, as these resistant organisms can be transmitted to humans either through the food chain or through direct contact [4].

The spread of “superbugs”, which are microorganisms resistant to most antibiotics, has escalated the threat of drug-resistant infections to a concerning level worldwide. Recognized as one of the top three major public health risks by the WHO, AMR is now the third leading cause of death, trailing only cardiovascular diseases [21]. In 2019, around 1.27 million deaths were associated with infections resistant to antimicrobials, and nearly 5 million deaths were connected to infections resistant to drugs [21,22]. These numbers are projected to soar to 10 million per year by 2050, surpassing deaths from cancer [21]. Methicillin-resistant Staphylococcus aureus (MRSA) is a bacteria strain that is resistant to several antibiotics, including methicillin and other beta-lactams. Staphylococcus aureus is a common bacterium found on the skin and in the nasal passages of healthy people, and it typically does not cause any issues. However, when it becomes resistant to antibiotics like methicillin, it can cause infections that are difficult to treat [23]. MRSA infections can range from mild skin infections to more serious and potentially life-threatening infections such as bloodstream infections, pneumonia, and surgical site infections. MRSA is a significant public health concern because it is resistant to many commonly used antibiotics, making it challenging to treat and control. MRSA has led to a significant death toll from antimicrobial-resistant infections globally [24]. Presently, at a global level, about 3.5% of people with active tuberculosis (TB) and 18% of those who have been treated for TB before are diagnosed with multidrug-resistant TB (MDR-TB). There is increasing worry about extensively drug-resistant TB (XDR-TB) among many cases of MDR-TB [25]. Despite the crucial role antibiotics play in fighting bacterial infections, their incorrect use and overuse, including wrong doses and durations over many years, have created selection pressure, leading to the emergence of bacteria that are resistant to these drugs. In addition to their impact on human health, the misuse of antibiotics in animal feed in many developing nations has significantly contributed to the emergence and spread of AMR. This calls for heightened monitoring to understand the consequences of excessive and uncontrolled antibiotic use in animal feed, aiming to reduce the prevalence of drug-resistant bacteria [26].

Antibiotic resistance can affect human health in terms of both treating infections and preventing them in the context of prophylaxis for clinical procedures and actions. The impact of antibiotic resistance on human health is twofold. First, there are direct consequences on treatment, which manifest as treatment failure and complications. Secondly, there are indirect consequences on prevention, which affect the availability of effective treatment for immunocompromised patients like cancer chemotherapy, advanced surgical procedures like transplantation, and invasive procedures such as intubation or catheterization [27]. Efforts to develop new synthetic and naturally derived molecules for treating antimicrobial-resistant infections starkly contrast with the growing need for such novel antimicrobials. Major pharmaceutical companies have largely withdrawn from antibiotic discovery since the 1980s. As a result, there has been minimal expansion of their antibiotic portfolios since then. The last major discovery of broad-spectrum antibiotics, such as fluoroquinolones, occurred in the 1980s, with the introduction of fluoroquinolone to the market in 1987. Since then, there has been a notable lack of new antibiotic development, with only a few new antibiotic groups currently in the development pipeline [28]. The more we use antibiotics, the more resistance develops, meaning we can reduce resistance significantly by only using antibiotics when necessary. Considering that antimicrobials are essential for treating and preventing infectious diseases, it is critical to preserve the effectiveness of the ones we currently have, especially since there have not been any major discoveries of new antibiotics in recent years.

This review was undertaken to emphasize the importance of society in AMR. Firstly, public awareness and education play a pivotal role in combating this global threat. By understanding the causes and consequences of AMR, individuals can make informed decisions about antibiotic usage, promoting responsible stewardship of these precious resources. Therefore, this literature review was undertaken following the methods described in the following section.

2. Methods

The present review includes studies published in the following databases: Science Direct, Scopus, and PubMed, which are relevant scientific databases concerning the focus of the study. The search terms used were “One Health” in “All fields” (1690), “Antimicrobial resistance development” in “Title” (235), and “Antimicrobial resistance impact on society” in “Title” OR “Abstract” OR “Keywords” (900). No language restrictions were imposed during the search. No date restrictions were imposed during the search. Therefore, all the studies fully published and in press until 29 May 2024 were considered and selected based on the most relevant information from the different aspects. From all the analyzed documents, the selection was made based on the relevance of information included in the Title, Keywords and Abstract by the author.

Articles were included based on the following criteria: (i) The study was based on the AMR influence on society (94); (ii) The study was based on the society influence on AMR (96); (iii) The study considered the explanation of AMR development (60); (iv) The study presents One Health approach on antimicrobial resistance (40). Studies may belong to more than one group (i; ii; ii, or iv) once the information is interconnected; therefore, a total of 128 studies were selected. From the 128 studies, 28 were chosen as an introduction; 96 were selected to analyze factors contributing to AMR; 92 were selected for this section to analyze strategies to combat AMR and antimicrobial resistance influence on and from society (4 were also chosen for the introduction); 16 studies were important to support discussion, conclusions, and future directions (8 were selected for this section, and 8 were also selected for the previous sections).

3. Chronology of Key Antibiotic Discoveries and the Rise of Antibiotic Resistance

The beginning of the modern antibiotic era can be traced back to Paul Ehrlich’s discovery of arsphenamine (salvarsan) and neosalvarsan in 1910, which were synthetic prodrugs used in cases of syphilis caused by Treponema pallidum [29]. In the early 20th century, scientists were fervently seeking solutions to combat infectious diseases that ravaged populations worldwide. In 1932, German chemist Gerhard Domagk and his team made a breakthrough discovery while investigating dyes. They found that a compound known as Prontosil, a red dye synthesized from azo dyes, had remarkable antibacterial properties. Further experimentation revealed that Prontosil effectively treated streptococcal infections in mice. This groundbreaking finding led to the development of the first commercially available antibiotic, which revolutionized the treatment of bacterial infections and saved countless lives. Domagk’s discovery of Prontosil laid the foundation for the subsequent development of other antibiotics, ushering in a new era in medicine and profoundly impacting global healthcare practices [29]. In 1928, Sir Alexander Fleming, a Scottish physician and microbiologist, stumbled upon the antibiotic properties of penicillin, derived from a mold called Penicillium rubens [30]. This discovery marked the beginning of the golden era of antibiotic exploration, which reached its peak in the mid-1950s. The period from the 1940s to the 1960s is often referred to as the “Golden Age” of antibiotic discovery, during which most of the antibiotics still in use today were found [28]. However, since then, there has been a gradual decline in the discovery of new antibiotics, accompanied by the emergence of drug-resistant bacteria. The problem of bacteria becoming resistant to antibiotics has been acknowledged almost since the beginning of the antibiotic era [28]. A few years before penicillin became widely used as a treatment in 1940, scientists identified the first strain of Staphylococcus bacteria that was resistant to penicillin. Then, in 1959, methicillin was introduced as a new type of penicillin that was resistant to penicillinase. In 1960, just a year after methicillin was introduced, a strain of Staphylococcus bacteria that was resistant to methicillin was reported [31].

The discovery of vancomycin stands as a testament to the ingenuity of scientific inquiry. In the mid-20th century, as bacterial resistance to antibiotics became increasingly problematic, researchers intensified their efforts to discover new antimicrobial agents. In 1953, Edmund Kornfeld and colleagues at Eli Lilly and Company isolated vancomycin, a glycopeptide, from a soil sample collected in Borneo. Initially, its potential as an antibiotic was overlooked due to its toxicity and narrow spectrum of activity. However, in the early 1960s, it was rediscovered and found to be remarkably effective against certain antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus and Enterococcus species [28]. Vancomycin’s unique mechanism of action, which disrupts bacterial cell wall synthesis, made it a valuable tool in combating infections that were resistant to other antibiotics. The emergence of strains of vancomycin-resistant coagulase-negative Staphylococci (CoNS) around 1979 presented a concerning development in the realm of antimicrobial resistance. CoNS, once considered relatively innocuous compared to their more virulent counterparts like Staphylococcus aureus, have now become increasingly problematic due to their ability to acquire resistance to multiple antibiotics, including vancomycin. Ten years later, vancomycin-resistant Enterococcus (VRE) was described [32]. Enterococcus species once considered relatively harmless inhabitants of the human gastrointestinal tract, began to pose a formidable challenge in healthcare settings due to their ability to acquire resistance to multiple antibiotics, including vancomycin. The first documented case of VRE was reported in Europe in the late 1980s, followed by a rapid spread across the globe. This emergence of VRE strains presented a serious threat, particularly in hospitals and long-term care facilities, where vulnerable patients are at heightened risk of infection. The rise of VRE highlighted the urgent need for enhanced infection control measures, prudent antibiotic use, and the development of novel antimicrobial agents to combat resistant bacteria [33]. Despite these challenges, ongoing research and collaborative efforts continue in the pursuit of effective strategies to mitigate the impact of VRE and other antimicrobial-resistant pathogens on public health. Over time, the effectiveness of vancomycin against Staphylococcus aureus decreased, with reports of vancomycin-intermediate Staphylococcus aureus (VISA) in 1997 and vancomycin-resistant Staphylococcus aureus (VRSA) in 2002 [34].

In 1945, cephalosporin, an antibiotic belonging to the β-lactam class, was discovered, and it was first used in clinical settings in 1964 to address cases of bacteria resistant to penicillin. Since then, there have been several advancements in cephalosporins, leading to the development of multiple generations, with the fifth generation being the most recent one currently accessible. Initially, cephalosporin showed outstanding effectiveness, particularly against Gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs) [21]. However, until recently, resistance has emerged up to the fourth generation of cephalosporins.

Another significant antibiotic is tetracycline, which was identified in 1950 and proven effective against various common infections, including gastrointestinal illnesses. However, over time, bacteria have developed mechanisms to evade the effects of tetracycline, rendering it less effective or ineffective in combating infections. One of the primary mechanisms of resistance involves the production of proteins that actively pump tetracycline out of bacterial cells, preventing its accumulation at concentrations necessary for bactericidal or bacteriostatic effects. Additionally, bacteria may acquire genetic mutations that alter the structure of the ribosomal binding sites targeted by tetracycline, reducing its affinity for these sites and diminishing its ability to inhibit protein synthesis. The widespread use of tetracycline in agriculture, veterinary medicine, and human healthcare has contributed to the selection pressure driving the evolution of resistance in bacterial populations. As a result, infections caused by tetracycline-resistant bacteria pose challenges for clinicians seeking effective treatment options [35].

Levofloxacin, a third-generation fluoroquinolone antibiotic, was introduced to the list of antibiotics in 1996, but unfortunately, in the same year, cases of Pneumococcus bacteria resistant to levofloxacin were reported [36]. Carbapenem, a class of β-lactam antibiotics, was introduced in 1980 and reserved as a last-resort medication for treating infections caused by enterobacterales, particularly in cases where cephalosporins were ineffective. As its usage grew from the 1990s to the 2000s, instances of carbapenem-resistant enterobacterales (CREs) began to emerge, with reports from various countries surfacing since 2006 [37]. Looking at the timeline of antibiotic discovery, it is clear that pharmaceutical companies introduced new classes of antibiotics for only about two decades, spanning from 1960 to 1980. After that, the pace of discovery dramatically slowed down until recent times. This stark contrast between the emergence of drug-resistant pathogens and the development of new antibiotics has led critics to predict the looming arrival of a post-antibiotic era [21]. The timeline illustrating the discovery of major antibiotics and their resistances, as well as the appearance of important resistant microorganisms, is presented in Figure 1.

Antimicrobial resistance (AMR) is a critical factor in the emergence of superbugs, bacteria that have evolved to resist multiple antibiotics, making infections difficult or impossible to treat. Overuse and misuse of antibiotics accelerate this resistance, allowing bacteria to survive and adapt. The accumulation of resistance leads to the appearance of superbugs through a process of natural selection and genetic adaptation. Superbugs are microorganisms that have developed resistance to the antimicrobial treatments typically used against them, encompassing bacteria and fungi that resist multiple or all available drugs. Unfortunately, there are often limited or no effective treatment options for infections caused by superbugs. In hospitals, healthcare-associated infection (HAI) bacteria are considered superbugs because most available antibiotics are ineffective against them. Infections caused by superbugs significantly increase both the likelihood of illness and death, as treatment options for these infections are severely limited. Moreover, treating these infections often incurs high costs and necessitates prolonged hospital stays [38].

4. Factors Contributing to AMR

AMR is influenced by various complex elements, encompassing inherent characteristics of microorganisms as well as numerous environmental elements involving both medical practitioners and the general public. Environmental elements include aspects such as population density and overcrowding, rapid transmission facilitated by mass travel, poor sanitation conditions, ineffective infection control measures, and extensive use of antimicrobials in livestock. Drug-related elements encompass issues like the presence of counterfeit or substandard drugs in the market, as well as the unrestricted availability of antimicrobial medications without prescription. Patient-related elements involve behaviors such as poor adherence to prescribed treatments, socioeconomic challenges like poverty and lack of education, self-medication practices, and misconceptions about antibiotic use. Physician-related elements encompass aspects such as inappropriate prescribing practices, inadequate dosing of medications, and gaps in knowledge or training among healthcare providers [39].

These elements are interconnected and usually organized into six AMR contributor factors: (i) antibiotic misuse; (ii) inappropriate prescription practices; (iii) scarcity of next-generation antibiotics; (iv) livestock use of antibiotics; (v) mobility, and (vi) lack of knowledge [16,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71].

4.1. Antibiotic Misuse

Excessive and incorrect use of antibiotics in humans and animals has sped up the development of antibiotic resistance. Studies have shown a clear link between overuse and the rise of resistance in bacteria. Despite repeated warnings from health authorities, the problem persists globally, and it appears we are reaching a critical stage where reversing this trend is becoming increasingly difficult [47]. Each of these factors contributes to the emergence and spread of antimicrobial resistance, underscoring the need for comprehensive strategies to address this global health challenge.

Studies have found that many people worldwide, especially those without formal education, hold misconceptions about antibiotics. For instance, some believe antibiotics can treat viral illnesses like the cold or flu. Additionally, antibiotics are often prescribed quite frequently for patient care, especially in many developing nations where diagnostic resources are limited [16]. The use of antibiotics without a clear need is a prime example of how antibiotics are often misused. This misuse is exacerbated when antibiotics are available without a prescription for both humans and animals, as over-the-counter drugs. The lack of clear antibiotic policies and treatment guidelines, especially common in developing nations, also contributes to this problem. Additionally, health workers, pharmacists, and veterinarians in many underdeveloped areas tend to overprescribe antibiotics. In some cases, poor-quality antibiotics in the supply chain worsen the situation of antibiotic resistance [16,47,48,64,65,67,69].

4.2. Inappropriate Prescription Practices

Improperly prescribed antibiotics play a significant role in promoting antimicrobial resistance (AMR) [40,41,44,52,59,60,62,63,66]. This refers to situations where antibiotics are prescribed when they are not needed, the wrong type of antibiotic is chosen, or the dosage and duration are incorrect [50]. Research indicates that about half of hospitalized patients receive at least one unnecessary antibiotic during their stay. While it is ideal for antibiotics to be prescribed based on bacterial isolation and susceptibility testing, a Centers for Disease Control and Prevention (CDC) report from 2017 found that about a third of hospital patients received antibiotics without adequate testing, and these prescriptions often continued for longer than necessary [45]. The situation is even more concerning in nursing homes, where 25–75% of antibiotic prescriptions are incorrect or inappropriate in terms of dosage and duration [53]. Furthermore, doctors sometimes unnecessarily prescribe long courses of antibiotics or give inappropriate doses, either due to financial incentives from pharmaceutical companies or to meet patient expectations, especially in developing countries [53].

4.3. Scarcity of Next-Generation Antibiotics

The pressing issue of antibiotic resistance calls for immediate action from pharmaceutical companies to develop new and innovative antibiotics [44]. Despite repeated appeals from the WHO, there has been a notable lack of progress in this area. Alarmingly, of the 51 recently developed antibiotics, only 8 are genuinely innovative in treating infections caused by resistant bacteria; the rest are essentially modifications of existing drugs. Consequently, there is concern that these new drugs may soon become ineffective due to resistance. This scarcity of novel antibiotics has severely compromised the management of drug-resistant conditions like tuberculosis, urinary tract infections, pneumonia, and certain Gram-negative infections, particularly affecting vulnerable populations such as the elderly [41]. Regulatory hurdles and financial risks are cited by pharmaceutical companies as major obstacles to the production of new antibiotics, leading many to scale back their investments in research and innovation. Several pharmaceutical companies have ceased antibiotic production altogether. Focusing on profitability, these companies have shifted their focus toward producing drugs for chronic diseases rather than infectious ones [41,52,56,58,60].

4.4. Livestock Use of Antibiotics

The increase in antimicrobial resistance in livestock influences human health by facilitating the transfer of resistant bacteria and resistance genes, creating a reservoir of resistance that can spread through direct contact, food consumption, environmental pathways, and global trade, thereby complicating the treatment of infections in humans [72].

The use of antibiotics in raising livestock has seen a significant rise in many developing nations, primarily driven by the growing demand for animal protein. However, this practice is exacerbating AMR due to the presence of antibiotic residues in animal-derived products such as meat, milk, and eggs as well as in excretory products. Antibiotics are being administered indiscriminately for various purposes, including treating animal diseases, promoting growth, improving feed conversion efficiency, and preventing illnesses [60]. This trend is more pronounced in developing countries, driven by the desire to increase profits from food animal farms and exacerbated by the lack of government regulations. In the United States, around 70% of medically important antibiotics are sold for use in animals, raising significant concerns. Moreover, the antibiotic used in veterinary practice often overlap with those prescribed for human use, creating a worrisome connection between animal and human antibiotic usage [26,43,46,49,63].

4.5. Mobility

Human mobility plays a significant role in the rise and widespread dissemination of antibiotic-resistant bacteria, shaping the landscape of antimicrobial resistance on a global scale. The easy accessibility of modern transportation routes not only by humans but also by animals and goods significantly impacts the spread of AMR. As people travel for various reasons such as tourism, business, migration, and healthcare, they inadvertently carry bacteria, including resistant strains, with them to different regions and communities [51,55,57]. This movement facilitates the spread of resistant bacteria beyond local boundaries, contributing to the globalization of antimicrobial resistance. Travel-related factors such as international air travel, mass transit, and tourism hubs create high-density environments where bacteria can easily transfer between individuals and surfaces. Additionally, medical tourism, where individuals seek healthcare services in countries with different antimicrobial prescribing practices, can introduce resistant bacteria to new settings. Furthermore, migration and displacement due to conflicts, natural disasters, or economic reasons can lead to the mixing of bacterial populations and the transmission of resistant strains between populations. Once introduced into new environments, antibiotic-resistant bacteria can establish reservoirs and disseminate through various pathways, including person-to-person contact, contaminated food and water, healthcare settings, and environmental sources. Inadequate sanitation, poor infection control practices, and overuse or misuse of antibiotics further exacerbate the problem, creating ideal conditions for the selection and spread of resistant bacteria. The interconnectedness of global travel networks and the movement of people underscore the need for coordinated international efforts to combat antimicrobial resistance. Strategies such as surveillance systems to monitor resistance patterns, improved infection control measures, judicious antibiotic use, and public awareness campaigns are essential for mitigating the impact of human mobility on the spread of antibiotic-resistant bacteria. By addressing antimicrobial resistance as a global health priority, we can work toward preserving the effectiveness of antibiotics for future generations [46]. Travelers, upon returning to their home countries, often unknowingly carry antimicrobial-resistant organisms acquired from the regions they visited. Studies have demonstrated that these resistant bacteria can persist in the body for up to twelve months after traveling to areas with high levels of AMR, thereby increasing the risk of transmission among vulnerable populations [54].

4.6. Lack of Knowledge

There is evidence showing that both healthcare workers and the general public do not always know how to use antibiotics properly or understand how antibiotic resistance develops [42]. To tackle this issue, we need surveillance systems to understand the extent of the problem and to plan interventions like antimicrobial stewardship programs. Unfortunately, we lack comprehensive data on antibiotic use and the status of antibiotic resistance globally, which makes it hard to take effective action. Surveillance data are crucial because they help us pinpoint where to focus our efforts. To address this problem and implement effective interventions, we need collaboration among various stakeholders like international agencies, medical and veterinary professionals, agricultural industries, and consumers. But first, we need to fill the gaps in our understanding of antibiotic use and resistance [68].

The clinical implications of AMR are significant and encompass several key concerns undermining the effectiveness of treating various types of infections. The emergence and spread of new resistant mechanisms pose a threat to treating common illnesses like urinary tract infections, upper respiratory tract infections, typhoid, and influenza. This can lead to treatment failure, long-term health issues, or even death. Moreover, the success rates of critical medical procedures such as cancer chemotherapy, organ transplantation, and routine dental treatments are at risk due to AMR, unless new medications are developed. Treating infections caused by AMR microorganisms often requires prolonged therapy with costly medications, leading to increased healthcare expenses and the need for expensive alternative drugs [45,61,70,71].

Table 1. Contributing factors to AMR.

Contributing Factors	Main Drivers	References
Antibiotic misuse	Humans (patients, health workers, pharmacists, and veterinarians)	[16,47,48,64,65,67,69]
Inappropriate prescription practices	Medical doctors and veterinarians	[40,41,44,45,50,52,53,59,60,62,63,66]
Scarcity of next-generation antibiotics	Pharmaceutical companies	[41,44,52,56,58,60]
Livestock use of antibiotics	Farmers and livestock producers and veterinarians	[26,43,46,49,60,63]
Mobility	Humans, animals, and goods	[46,51,54,55,57]
Lack of knowledge	Healthcare workers and the general public	[42,45,61,68,70,71]

summarizes important factors contributing to AMR and the corresponding main drivers.

5. Strategies to Combat AMR

Antimicrobial resistance poses a significant threat not only to human health but also to animals, plants, and the environment as a whole. Just as humans can harbor multidrug-resistant (MDR) bacteria, animals can also serve as reservoirs for these organisms, which can be transmitted through close contact or the consumption of animal-derived foods. Addressing the growing issue of antimicrobial resistance requires concerted efforts that transcend individual government departments or organizations. It necessitates coordinated action and collaboration across various sectors, including healthcare, agriculture, animal production, finance, trade, and education, both at national and international levels. This collaboration can take different forms, including horizontal collaboration, which involves cooperation across different sectors within a country, and vertical collaboration, which spans various levels within a country, regionally, and internationally [73].

We urgently need to address the overprescription of broad-spectrum antibiotics by physicians for minor ailments, and we must closely monitor the use of antimicrobials in animals by veterinarians. To combat AMR, we need to focus on rational antibiotic prescribing practices, limit the use of preventive antimicrobials, educate patients about antibiotics, ensure adherence to prescribed antibiotic regimens, and maintain proper hospital hygiene through antimicrobial stewardship efforts. The World Health Assembly has set out five key plans of action to tackle AMR. These involve raising awareness and comprehension of antimicrobial resistance, boosting understanding through surveillance and research, putting into practice efficient sanitation and hygiene measures, refining antimicrobial use in both human and animal health, and encouraging sustainable investment in new medications, diagnostic tools, and vaccines [74].

5.1. Antimicrobial Stewardship Programs

Antimicrobial stewardship programs (ASPs) are initiatives implemented in healthcare settings to optimize the use of antimicrobial agents to improve patient outcomes, minimize antimicrobial resistance, and reduce the spread of healthcare-associated infections. These programs are designed to promote the judicious use of antibiotics and other antimicrobial medications through a coordinated approach involving healthcare providers, pharmacists, infection control specialists, and other stakeholders [75].

The goals of ASPs include the following: (i) Promoting appropriate antimicrobial use. ASPs aim to ensure that antimicrobial medications are prescribed only when necessary and are chosen based on the best available evidence regarding their effectiveness and safety. This helps to minimize the overuse or misuse of antibiotics, which can contribute to the development of antimicrobial resistance; (ii) Preventing healthcare-associated infections: By optimizing antimicrobial use, ASPs help to reduce the incidence of healthcare-associated infections caused by antibiotic-resistant bacteria. This is achieved through measures such as prescribing the appropriate antibiotic at the right dose and duration, as well as implementing infection prevention and control measures to limit the spread of resistant organisms within healthcare facilities; (iii) Improving patient outcomes: ASPs aim to improve patient outcomes by ensuring that patients receive the most effective antimicrobial therapy for their condition. This may involve tailoring antimicrobial treatment regimens to individual patients based on factors such as their medical history, underlying conditions, and the results of diagnostic tests; (iv) Reducing healthcare costs [76,77]. By promoting appropriate antimicrobial use, ASPs can help to reduce healthcare costs associated with the unnecessary use of antibiotics, treatment failure due to antimicrobial resistance, and the management of healthcare-associated infections. This can result in cost savings for healthcare institutions and payers [75,78,79].

Key components of ASPs may include the development of antimicrobial guidelines and protocols, the implementation of antimicrobial stewardship interventions such as prospective audits and feedbacks, antimicrobial de-escalation, and dose optimization, as well as education and training for healthcare providers and patients. Overall, ASPs play a crucial role in combating antimicrobial resistance and improving patient care by promoting the responsible use of antimicrobial agents in healthcare settings. By working collaboratively across disciplines and implementing evidence-based strategies, ASPs contribute to the preservation of antimicrobial effectiveness for future generations [80,81,82,83,84]. The WHO has also imposed regulations for the use of antibiotics in animals as discussed in the next section [85,86].

5.2. Reduced Use of Antibiotics in Animals

Reducing antibiotic use in animals diminishes the development and spread of resistant bacteria, leading to fewer resistant infections in humans, preserving the effectiveness of existing antibiotics, and contributing to the overall global effort to combat antimicrobial resistance. Particularly these measures can decrease selective pressure and reduce transmission pathways breaking the cycle of resistance [87].

The WHO has urged for more stringent regulations regarding the use of medically important antibiotics in animals to address the challenges of antimicrobial resistance. Additionally, it advocates for a significant reduction in and eventual elimination of antibiotic use for growth promotion and primary disease prevention purposes in animals. However, antibiotics can still be used for disease prevention in animals if an infection has been diagnosed in other animals within the same group, such as a flock, herd, or fish population [85,86].

As alternatives to antibiotic use in animals, the WHO recommends implementing improved hygiene practices, providing probiotics or nutritional supplements in animal feed, enhancing vaccination strategies, and making changes to animal husbandry practices [65,88,89,90,91]. These measures aim to promote animal health and welfare while reducing reliance on antibiotics and mitigating the development of antimicrobial resistance [65,88,89,90,91].

5.3. Creating New Medications and Vaccines

Given the rapid emergence of resistance to each new type of antibiotic and the challenges in developing effective new drugs, it is crucial to pursue a comprehensive approach that includes both vaccine development and the creation of novel antibiotics. Addressing AMR requires increased investment in operational research and innovation to develop new antimicrobial agents, achieved through collaborative efforts between academia and industry at both national and international levels. Vaccines have long been used as preventive measures against infectious diseases and are recognized as essential tools for reducing the need for antimicrobial drugs, thus aiding in the fight against AMR. Unlike antibiotics, vaccines are not associated with the development of resistance. Therefore, there is significant potential in innovating and utilizing vaccines to target antimicrobial-resistant bacterial infections, particularly those caused by carbapenem-resistant enterobacterales and Acinetobacter baumannii. This strategy could play a crucial role in combating the transmission of AMR [68,92,93,94,95].

5.4. One Health Approach

The One Health approach seeks to achieve optimal health for people, animals, and the environment. It focuses on a wide range of sustainable development objectives and involves designing, implementing, and monitoring programs, policies, and research related to AMR surveillance. This approach aims to gather evidence and foster advanced intersectoral collaboration among humans, animals, plants, and their shared environment. AMR is a global health issue that impacts humans, animals, and the environment, making it a prime example of the One Health approach in action [68].

The essence of the One Health approach is built upon three fundamental principles known as the three Cs: communication, coordination, and collaboration. These principles emphasize the need for professionals from human health, animal health, and environmental sectors to effectively communicate, coordinate their efforts, and collaborate to address health challenges holistically. The key participants in implementing the One Health approach are often referred to as the three Ps: pharmacists, physicians, and patients. Additionally, other healthcare and epidemiology professionals play crucial roles in this collaborative approach. Together, they contribute their expertise and perspectives to promote the health and well-being of humans, animals, and the environment. In terms of animal health, veterinarians and agricultural workers are included, while ecologists and wildlife experts are considered environmental specialists [96]. The One Health strategy can contribute significantly to preventing AMR. This can be achieved through various means such as awareness campaigns, educational initiatives on antibiotic usage, advocacy efforts backed by political support, and the implementation of antimicrobial stewardship programs [97].

Figure 2 represents AMR interactions in a simplified scheme once antibiotic resistance is prevalent in humans, animals, and the environment, which are interconnected according to the One Health approach [98,99]. The environmental release of antibiotics and contact between resistant and non-resistant bacteria drive resistance. Water bodies and soil can act as reservoirs for resistance spread. Wildlife can acquire resistant bacteria through contact with livestock and wastewater. The misuse of antibiotics in animal farming promotes resistant bacteria, which can spread to humans and other animals through various interactions. Unmetabolized antibiotics excreted by animals further select for resistance in the environment.

Table 2. Main important strategies to combat AMR.

Strategy	Main Drivers	References
Antimicrobial stewardship programs	Regulatory agencies	[75,78,79,80,81,82,83,84,85,86]
Reduced use of antibiotics in animals	Veterinarians, farmers, and livestock producers	[65,88,89,90,91]
Creating new medications and vaccines	Pharmaceutical companies, research institutes, and universities	[68,92,93,94,95]
One Health approach	Farmers and livestock producers, veterinarians, pharmaceutical companies, regulatory agencies, industry organizations, and consumers	[68,96,97,98,99]

summarizes strategies to combat AMR and the corresponding main drivers.

6. Antimicrobial Resistance and Society

6.1. General Considerations

AMR is a societal challenge that demands collective action and awareness. In the context of antibiotic resistance, society can be defined as a collective of individuals, institutions, and communities whose health, well-being, and social structures are intricately interconnected and impacted by the effectiveness of antibiotics. The rise of antibiotic resistance threatens this societal fabric by undermining the ability to treat common infections, leading to increased mortality, healthcare costs, and the potential collapse of modern medical practices. As a societal issue, antibiotic resistance requires a coordinated response involving public health policies, education, and responsible use of antibiotics to safeguard the health of current and future generations [21,100].

In the intricate tapestry of society, every thread contributes to the fabric of AMR, and every individual holds a stake in its resolution. The importance of society in AMR is multifaceted. Firstly, public awareness and education play a pivotal role in combating this global threat. By understanding the causes and consequences of AMR, individuals can make informed decisions about antibiotic usage, promoting responsible stewardship of these precious resources [101].

Moreover, societal behaviors and practices directly influence the spread of resistant microbes. From healthcare settings to agriculture and beyond, societal norms shape the selective pressure driving the evolution of resistance. By embracing practices that minimize the risk of resistance emergence, such as proper hygiene, vaccination, and prudent antibiotic use, communities can collectively mitigate the spread of resistant pathogens [102].

Additionally, the impact of AMR reverberates throughout society, transcending geographical and socioeconomic boundaries. Infections once easily treatable may become untreatable, posing grave risks to public health, economic stability, and societal well-being. AMR threatens not only individual health but also healthcare systems’ capacity to deliver essential services, exacerbating inequalities and straining resources [103].

Conversely, the importance of AMR in society cannot be overstated. It serves as a sobering reminder of the interconnectedness of global health and the fragility of our antimicrobial arsenal. In a world where antimicrobials underpin modern medicine, from routine surgeries to cancer treatments, the erosion of their efficacy jeopardizes countless lives and undermines decades of medical progress [21].

From individual health to economic stability, the repercussions of AMR are felt globally, underscoring the urgent need for concerted action to address this growing threat [104]. One of the most immediate consequences of antimicrobial resistance is the rise in treatment failures and mortality rates associated with resistant infections. Common infections, once easily treatable with antibiotics, become increasingly difficult to manage, leading to prolonged illness, disability, and in some cases, death. The loss of effective antimicrobial therapies undermines the cornerstone of modern medicine, posing a grave threat to public health. Another important consequence is healthcare burden: antimicrobial-resistant infections impose a significant burden on healthcare systems, straining resources, and compromising patient care. Longer hospital stays, increased healthcare costs, and the need for more intensive interventions contribute to the escalating economic toll of AMR [105]. Moreover, the emergence of resistant pathogens complicates infection control measures, heightening the risk of healthcare-associated outbreaks and further exacerbating the strain on healthcare infrastructure. The economic ramifications of AMR extend beyond the healthcare sector, affecting productivity, trade, and economic growth [106]. The direct costs of treating resistant infections, including hospitalization, medication, and follow-up care, place a considerable financial burden on individuals, families, and healthcare payers. Additionally, the indirect costs stemming from lost productivity, absenteeism, and reduced workforce participation further compound the economic impact of AMR, undermining socioeconomic development and stability. Antimicrobial resistance also poses a threat to food security and agricultural sustainability [49,107]. The widespread use of antimicrobials in livestock farming contributes to the emergence of resistant bacteria in food animals, which can subsequently enter the food chain and pose a risk to human health. Moreover, the loss of effective antimicrobial therapies in veterinary medicine compromises animal health and welfare, jeopardizing the global food supply and agricultural livelihoods. AMR transcends national borders and represents a significant threat to global health security. Resistant pathogens know no boundaries and can spread rapidly across continents through travel, trade, and migration. The emergence of pan-resistant bacteria, resistant to multiple classes of antimicrobials, poses a particularly alarming scenario, where infections become virtually untreatable using existing therapies. Addressing AMR requires international cooperation, surveillance, and capacity-building efforts to prevent the spread of resistant pathogens and mitigate the risk of global health crises [108].

6.2. AMR in Developing Countries

In developing countries, where healthcare infrastructures often grapple with limited resources and accessibility, the implications of antimicrobial resistance are stark. These regions frequently face higher burdens of infectious diseases due to factors like poor sanitation, overcrowding, and inadequate healthcare facilities [109,110]. Consequently, antibiotics and other antimicrobial agents become indispensable tools in combating these diseases. Developing countries often face substantial economic losses due to decreased productivity, increased healthcare expenditures, and losses in agricultural and livestock sectors. The spread of resistant pathogens can devastate agricultural communities reliant on livestock for their livelihoods, disrupting food production chains and exacerbating food insecurity. The importance of antimicrobial resistance in society, particularly in developing countries is unquestionable, and only through collaborative action can we hope to mitigate the growing threat posed by antimicrobial resistance and safeguard the health and well-being of present and future generations [65,66,111,112].

6.3. AMR in Elderly Centers

As the global population ages, the importance of elderly centers becomes increasingly critical. These centers serve as vital hubs for the elderly, providing a range of services and fostering a sense of community, which is essential for their well-being. They provide essential social, medical, and educational services that enhance the quality of life for older adults. As the number of elderly individuals continues to rise, the expansion and support of such centers will be crucial in meeting their needs and ensuring a healthier and happier aging population [113]. As the population ages and the number of older adults residing in these centers increases, addressing AMR becomes increasingly critical. Elderly individuals are particularly vulnerable to infections, and the rise of resistant pathogens can have severe implications for their health and well-being [100].

Firstly, elderly residents in care centers are at higher risk of infections due to factors such as weakened immune systems, the presence of chronic illnesses, and the frequent use of medical devices like catheters and feeding tubes. These factors make them more susceptible to acquiring infections, which can be more difficult to treat if the pathogens involved are resistant to standard antibiotics. Common infections in elderly centers, such as urinary tract infections, respiratory infections, and skin infections, can become life-threatening if caused by resistant bacteria [114]. Secondly, the close living conditions in elderly centers facilitate the rapid spread of infections. When a resident becomes infected with a resistant pathogen, it can easily spread to others through direct contact or contaminated surfaces [115,116]. This can lead to outbreaks that are challenging to control and can result in significant morbidity and mortality among residents. Effective infection control measures and judicious use of antibiotics are essential to prevent such outbreaks and protect the health of vulnerable elderly populations [115,116]. Moreover, the overuse and misuse of antibiotics in elderly centers contribute to the development and spread of AMR. In many cases, antibiotics are prescribed unnecessarily or for prolonged periods, which can promote the emergence of resistant strains of bacteria [117]. Implementing antibiotic stewardship programs in these settings is crucial to ensure that antibiotics are used appropriately. These programs involve guidelines for prescribing antibiotics, regular review of antibiotic use, and education for healthcare providers about the risks of overuse [117,118].

In addition to antibiotic stewardship, elderly centers must adopt comprehensive infection prevention and control practices [119]. This includes regular hand hygiene, proper sterilization of medical equipment, and isolation of infected residents when necessary. Staff training and awareness about AMR and infection control are vital components of these efforts. By implementing strict hygiene protocols and educating staff, elderly centers can reduce the incidence of infections and the spread of resistant pathogens [119,120].

The importance of surveillance and monitoring cannot be overstated. Regular monitoring of infection rates and antibiotic resistance patterns helps identify trends and outbreaks early. This enables timely interventions to contain the spread of resistant infections. Collaboration with public health authorities and participation in national and global AMR surveillance networks enhance the ability to track and respond to resistance threats effectively [119,120].

7. Discussion

The evolution of bacteria’s resistance to antimicrobials is an ongoing process, driven by either genetic mutations within their chromosomes or the acquisition of resistance genes through horizontal gene transfer. Over the past two decades, this gradual development of AMR has emerged as a significant threat to global public health, now recognized as the foremost health concern of the 21st century. This situation severely limits the effectiveness of treatment options, as MDR bacteria are increasingly prevalent in various common infections worldwide, including respiratory, urinary, sexually transmitted, and tuberculosis infections. However, the development and availability of new antibiotics have not kept pace with the rapid evolution of AMR, lagging significantly since the 1980s. Consequently, the outlook for successful antimicrobial therapy appears grim, given the unprecedented rise of infections caused by MDR pathogens and the scarcity of new antimicrobial agents being developed. Without globally coordinated efforts to combat the ongoing trend of AMR, the prospect of entering a postantibiotic era in the 21st century may become more than just a hypothetical scenario but a genuine threat [21].

Numerous factors are fueling the rise and spread of antimicrobial resistance worldwide, posing significant challenges for human and animal health alike. These resistant infections are tougher to manage, often resulting in treatment failures and additional complications, alongside substantial financial burdens on individuals and communities. Implementing judicious antibiotic practices, including the careful administration of antibiotics at the right doses and for the correct durations, stands as a crucial strategy to alleviate the selective pressure that fosters the emergence of resistant bacteria. Additionally, rigorously adhering to infection prevention and control protocols across all healthcare settings plays a pivotal role in containing the transmission of multidrug-resistant organisms [121].

AMR demands a cohesive and well-coordinated global response involving not only international governmental and non-governmental organizations but also a robust political commitment. Collaboration and integration across various sectors, including policymakers, researchers, public health experts, pharmaceutical companies, hospital administrators, leaders in the agriculture industry, and the general public, are essential in this effort. The overarching objective of this collective endeavor is to slow down the current trends of AMR, thereby reducing the health and economic burdens on society. Key strategies include implementing antimicrobial stewardship programs and ensuring strict adherence to antibiotic policies within healthcare facilities. Additionally, promoting good microbiology practices, enhancing surveillance and monitoring systems, reducing the over-the-counter availability of antibiotics, and limiting antibiotic use in food animals are vital steps [24,68,96,121,122,123].

Primary prevention remains the most effective approach to combat antimicrobial-resistant infections and curb their global transmission. While it is crucial to restore the effectiveness of current antibiotics by using them judiciously, there is an urgent need to focus on developing new and effective molecules, including both antibiotics and alternatives to antibiotics. Additionally, advancements in diagnostic technologies and vaccine development are imperative. Despite numerous attempts to tackle the challenges posed by antibiotic resistance and the necessary interventions, coordinated action is often lacking, particularly in terms of political will at both national and international levels [94,95,124,125].

The alarming rise of antimicrobial-resistant infections suggests that we could encounter significant setbacks in the medical, social, and economic realms within a short period. Without prompt and effective global coordination, the progress we have achieved in modern medicine could be threatened [12].

This study’s limitations include the difficulty of accounting for the varying socioeconomic and cultural factors influencing antimicrobial use across different regions. Moreover, the One Health approach emphasizes the interconnectedness of human, animal, and environmental health, and so obtaining comprehensive data from all sectors can be challenging. Gaps in data collection, especially in low-resource settings, may lead to incomplete or skewed findings due to unpublished information. Also, the rapidly evolving nature of antimicrobial resistance, driven by both natural adaptation and human practices, poses a challenge for keeping the study’s findings current and universally applicable.

8. Conclusions and Future Directions

In conclusion, the consequences of antimicrobial resistance on society are multifaceted and profound, impacting individual health, healthcare systems, economies, food security, and global health security. Addressing this complex challenge requires a coordinated and multisectoral approach, encompassing healthcare, agriculture, policy, research, and community engagement. By prioritizing antimicrobial stewardship, innovation, and collaboration, societies worldwide can mitigate the adverse effects of AMR and safeguard public health for future generations [21].

In essence, society, as the collective group of individuals, institutions, and communities that are interconnected by shared practices, behaviors, and policies related to health, medicine, and the environment, is both a key player in the fight against AMR and a frontline victim of its consequences. By fostering a culture of collective responsibility, promoting sustainable practices, and prioritizing antimicrobial stewardship, societies worldwide can confront this existential threat and safeguard the health and well-being of future generations [126].

As a member of society, individuals can contribute to this effort by (i) using antibiotics responsibly; (ii) practicing good hygiene; (iii) following vaccination protocols; (iv) supporting policies limiting antibiotic use in agriculture; (v) educating yourself and others by understanding the issue; (vi) disposing of antibiotics properly; (vii) being cautious with travel (follow travel health advice). By following these recommendations, individuals can play a significant role in preventing the spread of antimicrobial resistance, thereby safeguarding the effectiveness of antibiotics for future generations [21,126].

Enhancing access to high-quality and affordable medicines, vaccines, and diagnostics is essential in the fight against AMR. By ensuring that effective treatments and tools are available to all, we can better manage infections and reduce the misuse and overuse of antibiotics. Additionally, enforcing legislation to regulate antimicrobial use is crucial. By implementing policies that promote responsible prescribing practices and restrict the inappropriate use of antimicrobials, we can help slow the emergence and spread of resistant bacteria. Together, these measures contribute to our collective efforts to address the challenge of AMR and safeguard the effectiveness of antimicrobial treatments for future generations [21,127].

The convergence of habitats brings together wildlife, domestic animals, and humans, creating frequent interactions that pose risks to both human and animal health [128]. This emphasizes the need for a systematic approach that prioritizes restoring resilience across various biological systems—human, animal, and environmental—an approach known as “One Health”. Adopting this integrated and holistic multisectoral approach is crucial for coordinating activities across human, animal, and environmental domains to comprehensively understand the drivers of antibiotic resistance and mitigate its emergence in diverse settings. Surveillance studies that encompass humans, animals, and the environment are indispensable for assessing the spread of antibiotic resistance and monitoring emerging patterns. By embracing the principles of One Health and conducting collaborative surveillance efforts, we can effectively combat antibiotic resistance and safeguard the health of both current and future generations [98].