Healthcare Facilities as an Emerging Source of Antimicrobial Resistance: A One Health Perspective

Abstract

Antimicrobial resistance (AMR), mostly resulting from the widespread use of antimicrobials in healthcare, veterinary, and agriculture, poses a significant challenge to global health. Healthcare facilities are hotspots of AMR due to high antibiotic consumption and the presence of highly susceptible populations. Moreover, there may be a dynamic exchange in AMR between healthcare infrastructures, human populations, animals, and the environment. To address these challenges, this review presents a One Health perspective, emphasizing the complex interconnections among many ecosystems. Furthermore, the development and dissemination of AMR in the healthcare environment, via surfaces and hands, have been critically investigated. Some of the neglected aspects that contribute to AMR, such as ventilation and wastewater, have also been addressed. The natural environment plays a crucial role as a reservoir for antimicrobial resistance genes (ARGs). The expected increase in AMR in the coming years will not only pose a challenge to public health but also to food security and environmental health. Hospitals should install advanced systems for treating wastewater to reduce the discharge of antimicrobials. Hospitals should also combine full water, sanitation, and hygiene (WASH) protocols with infection prevention and control (IPC) methods. These efforts are aimed at preventing infections and protecting public health and the environment. Other measures include advancing research to understand transmission pathways, increasing surveillance, reducing contamination in healthcare settings, implementing national plans for stewardship, and globally sharing resources and targets to reduce AMR.

1. Introduction

Antimicrobial resistance (AMR) in the environment has emerged as a major global challenge for public and environmental health in the 21st century [1,2]. The accumulation of genetic changes in pathogens over time contributes to the development of AMR. Its emergence and spread have been further accelerated by various human activities, particularly the excessive or subtherapeutic use of antimicrobials in the treatment and prevention of infections.

The emergence of AMR is a natural and widespread phenomenon among bacterial species in both aquatic and terrestrial ecosystems [1,3]. It complicates the treatment of infections, increasing the risk of disease progression, transmission, or even disability and death [4]. The rise of AMR also compromises the safety and effectiveness of lifesaving procedures, both in healthcare facilities and at the household level. AMR presents significant risks to human and ecosystem health, as novel antibiotic-resistant strains can emerge in waste, receiving waters, and soil, where horizontal gene transfer and environmental dissemination may amplify their spread [5]. In addition, the escalation of AMR in the veterinary and agricultural sectors has affected productivity, threatening food safety, food security, and environmental sustainability [6].

To effectively combat AMR, a One Health approach must consider human, animal, and environmental aspects. This includes improving surveillance systems, supporting stewardship programs, and investing in research and development of new antimicrobial treatments [4]. The One Health approach is also feasible for preventing and managing AMR because it tackles the core causes, drivers, and sources in the environment. It involves an understanding of a range of environmental components, including microorganisms, host organism vectors, and cultural and socioeconomic factors, which contribute to the spread of AMR and should be taken into account in its management [7,8].

AMR poses a significant challenge to global health and healthcare systems and it is considered one of their most pressing threats. Assessing the actual burden of AMR remains challenging due to the lack of comprehensive surveillance data and systems. Even though extensive literature is available regarding the AMR burden, most studies are restricted to areas such as incidence rates, mortality, length of hospital stay, and economic costs. Therefore, the current review aims to address existing research gaps and answer the following questions:

I.

How do healthcare facilities contribute to and experience the impacts of AMR within a One Health context?

II.

What are the current research challenges and potential solutions associated with AMR in healthcare?

This review aims to synthesize the current knowledge on AMR under a One Health approach, namely by emphasizing the interconnection between human, animal, and environmental health. By providing a holistic view of the AMR burden and management strategies, this paper seeks to inform researchers, key stakeholders, and policymakers in adopting multidimensional approaches to technologies and policies that address the global challenge of AMR. This review significantly contributes to the discussion by highlighting the relationship between healthcare facilities, the environment, and the One Health approach in the context of AMR. It presents a holistic One Health concept that emphasizes the commonly overlooked AMR drivers, resource restrictions, and fragmented solutions in the fight against AMR. This assessment opens the ground for a truly inclusive and effective global response by making specific recommendations for accountability structures, improved healthcare quality, universal coverage, and increased AMR funding. Furthermore, it lays the groundwork for future research by identifying critical gaps within healthcare facilities, allowing stakeholders and policymakers to develop informed and effective strategies for navigating the complex landscape of AMR mitigation and management.

2. Human Health Impacts of AMR

The increased development of AMR is a current issue with a long-standing association with antibiotic use [6]. An estimated 34.8 billion antibiotic doses are consumed annually, with global consumption increasing by 65% between 2000 and 2015 [9]. The agricultural sectors account for approximately 63,000–240,000 tons of antibiotics used per year [10]. Excessive or inappropriate use, such as self-medication or purchasing antibiotics without a prescription, and the lack of awareness and education among the public and healthcare professionals, are major contributors to the development and spread of AMR [11]. These contributing factors must be understood within a broader historical and global context.

The progression of AMR, along with key milestones such as the discovery of antibiotics, the emergence of resistance, alternative treatment efforts, and international policy responses, is illustrated in the chronological timeline in Figure 1. Antimicrobials play a vital role in the safety of human, plant, and animal health. However, the release of antimicrobials or their metabolites into the environment has emerged as a global issue, as they often contain high levels of biologically active substances that can promote the development of AMR [5]. The European Centre for Disease Prevention and Control (ECDC), the European Food Safety Authority (EFSA), and the European Medicines Agency (EMA) have found a negative correlation between bacterial susceptibility and the consumption of antimicrobials for both human and food-producing animals [12]. Moreover, the discharge of AMR-contaminated water poses risks to both aquatic and terrestrial ecosystems, subsequently exposing humans and animals to harmful consequences. According to the European Commission (EC), AMR may have caused the deaths of approximately 400,000 EU citizens since 2001 [5].

Healthcare waste and wastewater from healthcare facilities significantly contribute to the environmental spread of AMR. Nosocomial infections have been recorded in healthcare settings, with hospitalized patients experiencing the most severe outcomes. In high-income countries (HIC), the prevalence of nosocomial infections is approximately 7%, compared to 15% in low- and middle-income countries (LMIC) [13]. According to the World Health Organization (WHO), nearly 42.7 million of the 421 million people hospitalized globally each year have healthcare-associated infections (HAIs), a severe patient safety issue [14]. HAIs increase the workload of healthcare staff, including infection prevention and control teams, and impose a substantial economic burden on healthcare systems. For example, in 2017/2018, the UK’s National Health Service (NHS) spent £5.6 billion managing unhealed wounds, particularly those complicated by infections, compared to £2.7 billion spent on healed wounds [15]. A cohort study conducted in Ghana compared patients with bloodstream infections caused by resistant strains (i.e., third-generation cephalosporin-resistant enterobacteria and methicillin-resistant Staphylococcus aureus) to those infected with susceptible strains and uninfected controls [16]. The study found that the presence of resistant strains was associated with an increased length of hospital stay of 4 to 5 days, with additional treatment costs. In France, comparable findings showed a 1.6-day increase in hospital stay, contributing to national healthcare costs related to resistant infections [17].

Globally, estimates suggest that direct fatalities linked to AMR exceeded 1.2 million in 2019, with projections of reaching 10 million deaths annually by 2050 if effective measures are not implemented [2,6,18,19]. Reports indicate that AMR has been responsible for approximately 50,000 deaths in Europe and the United States of America alone, with thousands more occurring in other parts of the world [20,21]. In 2019, Escherichia coli was the most common cause of AMR-related mortality, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa [19]. Together, these AMR-related infections were directly responsible for over 929,000 deaths globally and contributed to an estimated total of 3.57 million deaths. The highest mortality rate was observed in Western Sub-Saharan Africa, reaching 27.3 deaths per 100,000 population [4]. If current trends continue, AMR could result in 2.4 million deaths across Europe, North America, and Australia between 2015 and 2050. Furthermore, global projections estimate that without effective intervention, AMR could lead to up to 10 million deaths annually and a cumulative global Gross Domestic Product (GDP) loss of $100.2 trillion by 2050 [2,4,6,22].

3. Key Drivers of AMR

AMR arises from a complex and dynamic interplay between microbial evolution, human activities, and industrial practices (Figure 2). While the development of AMR is a natural evolutionary process driven by genetic mutations among microorganisms, anthropogenic factors have profoundly accelerated its emergence, propagation, and global dissemination [23,24,25].

3.1. Mechanisms Leading to the Development of AMR

Bacterial development of AMR involves a diverse array of resistance mechanisms to survive antimicrobial exposure, including enzymatic drug degradation, target site alteration, increased efflux pump activity, and reduced membrane permeability. These mechanisms fall into three broad categories: intrinsic, acquired, and adaptive resistance [2,23]. Intrinsic resistance is innate to specific bacterial species, arising from inherent structural or functional features. Acquired resistance, by contrast, emerges through genetic mutations or horizontal gene transfer, and adaptive resistance refers to transient and reversible phenotypic changes induced upon antibiotic exposure, often mediated by dynamic shifts in gene expression [2,6,24]. Horizontal gene transfer (HGT), through transformation, transduction, and conjugation, further accelerates the spread of resistance genes across bacterial communities. Moreover, mobile genetic elements such as plasmids, transposons, and integrons, play important roles in gene exchange during conjugation, the most frequent and significant mechanism of HGT [26].

3.2. Factors Contributing to AMR Emergence, Spread, and Transmission

The emergence, spread, and transmission of AMR are fueled by numerous interconnected factors, with anthropogenic activities (e.g., agriculture, healthcare) and the environment acting as critical reservoirs and evolutionary incubators for resistant genes that sustain a complex network of microbial interactions under varying selective pressures [2,6].

3.2.1. Pharmaceutical Industry

The pharmaceutical industry represents a critical yet frequently underestimated contributor to the environmental burden of AMR [27]. The release of antimicrobials from pharmaceutical manufacturing into wastewater, especially when inadequately treated or directly discharged into the environment, creates hotspots of selective pressure, fostering ideal conditions for the emergence and dissemination of resistant bacteria [28]. The presence of antimicrobials in the environment promotes genetic mutations, facilitates HGT, and selects for resistant bacterial strains even at sub-inhibitory concentrations [29,30]. Addressing this issue requires stricter effluent regulations, advanced wastewater treatment, and international cooperation to enforce environmental discharge standards [25].

3.2.2. Healthcare Infrastructures

Human activities are major drivers of the global dissemination of AMR, with healthcare settings serving as key hotspots for resistance emergence and propagation, primarily due to excessive use, inappropriate dosing, and widespread self-medication of antimicrobials [24,25,26]. The overuse of antimicrobials exposes both pathogenic and commensal bacteria to selective pressure, increasing the likelihood of spontaneous resistance mutations. Conversely, the excessive and often empirical use of broad-spectrum antibiotics further contributes to AMR by disrupting the native microbiota and promoting the proliferation of opportunistic pathogens harboring resistance determinants [26,27]. In these settings, resistant bacteria can disseminate through direct contact with contaminated surfaces and medical devices (e.g., catheters, ventilators), and the hands of healthcare workers [31]. Primary healthcare centers have been reported as hotspots for AMR compared to secondary and tertiary healthcare facilities, largely due to improper use of antibiotics in the treatment of acute respiratory tract infections, a lack of robust stewardship standards in primary healthcare settings, and limited diagnostic capacity forcing practitioners to rely on empirical antibiotic use [32,33]. In contrast, higher-level healthcare facilities demonstrate better compliance with antibiotic prescription practices, adherence to guidelines, and greater access to diagnostic tools [34]. While existing evidence and published literature support these claims, further research across diverse contexts is required to draw more reliable conclusions.

In this way, healthcare settings act as AMR amplification hubs, not only because of high antibiotic consumption but also due to the presence of highly susceptible patient populations (immunocompromised, elderly, or critically ill), who are more vulnerable to colonization and infection [31]. Self-medication, often driven by a lack of regulatory control in many regions, particularly in LMICs, further exacerbates these issues by promoting inappropriate drug selection, incorrect dosing, and incomplete treatment courses [24]. These actions promote the development of resistant strains and multidrug resistance (MDR) infections within healthcare systems and the broader community [24]. Beyond clinical settings, the improper disposal of unused antibiotics and the release of untreated medical and industrial wastewater significantly contribute to environmental contamination [27]. These practices create additional reservoirs where environmental bacteria can acquire and disseminate resistance genes, amplifying the environmental dimension of AMR. Thus, human healthcare activities, through both direct clinical transmission and indirect environmental pathways, play a central role in the emergence, evolution, and global spread of AMR.

3.2.3. Companion Animals

Companion animals are recognized contributors to the spread of AMR due to their close contact with humans and shared environments [35]. Antibiotic use in veterinary medicine can select for resistant strains, particularly Pseudomonas spp. and Enterococcus spp., which show high resistance levels in pets [36,37]. Transmission of antibiotic-resistant bacteria occurs bidirectionally through contact, saliva, feces, urine, aerosols, and contaminated surfaces [35]. Addressing this public health concern requires understanding the role of pets in AMR development, improving surveillance, and applying a One Health approach. Current research gaps include limited tracking of transmission pathways, insufficient surveillance, and inadequate assessment of behavioral, regulatory, and environmental factors influencing AMR spread.

3.2.4. Agriculture and Animal Production

The use of antibiotics in animal husbandry and agriculture is highly associated with the emergence and spread of AMR, through excretion, manure application, and aquaculture runoff, which introduce residues and resistance genes into the environment [6,38,39,40]. In many countries, antibiotic use in food-producing animals exceeds that in human medicine [41]. However, in Europe, antimicrobial consumption in livestock has declined under the European Union’s “One Health” action plan, which restricts antimicrobial use [42]. By 2021, human antimicrobial consumption per biomass (125.0 mg/kg) exceeded that of food-producing animals (92.6 mg/kg) [12]. Besides therapeutic purposes, antibiotics are also used for growth promotion and disease prophylaxis in some countries; approximately 20% of World Organization for Animal Health (WOAH) member countries still allow growth-promoting use [43], although it has been banned in the EU since 2006 [44], and in the United States of America since 2017 [45,46,47].

Antibiotics are also used in plant agriculture to treat bacterial infections, such as Huanglongbing disease in commercial citrus [48]. Antibiotics present in manure applied to agricultural land may result in minimal losses (typically <5%) through leachate and surface runoff, potentially contaminating nearby water sources [49]. Yet, bovine sources, including feeding practices and manure management, have been associated with an increase of 34–80% in antibiotic resistance genes (ARGs) in riverbed sediments and surface waters, with detectible impacts extending up to 13 km downstream [50]. Not surprisingly, ARGs have been detected in water sources including groundwater, surface water, and even treated drinking water [51].

3.2.5. Dissemination in the Food Chain and Drinking Water

The use of antibiotics in plant and animal production can lead to the introduction of AMR into the human food chain. For example, in Saudi Arabia, lettuce, tomatoes, and cucumbers were found to contain AMR bacteria at concentrations ranging from 10⁷–10¹⁰ per 50 g of produce [52]. In Switzerland, AMR was detected in over 50% of foodborne pathogens (e.g., Campylobacter, Salmonella, Escherichia coli, Listeria) found in meat and seafood products [53]. In the United States, 21% of foodborne Salmonella outbreaks involved AMR strains, with a significantly higher hospitalization rate (28%) observed when clinically important resistance was present [54]. In China, notable similarities have also been identified between ARGs circulating in swine and those found in human populations [55].

In addition to food, humans may be exposed to AMR through water sources. In Spain, adult exposure to AMR Escherichia coli via tap water consumption has been estimated at up to 0.3 colony-forming units (CFU) per day [56], while exposure through recreational waters in Italy could reach 345 CFU per 100 mL [57]. ARGs have also been detected in ambient air, raising concerns about airborne transmission. These airborne ARGs are often associated with anthropogenic sources, particularly livestock facilities [58,59].

4. The Contribution of Healthcare Facilities to Environmental Exposure to AMR

Building upon the understanding of AMR emergence within healthcare environments, it is essential to compare these healthcare-associated drivers with those operating in other sectors to better contextualize their relative impact.

The healthcare sector exerts a disproportionately greater impact on the emergence and dissemination of AMR compared to other sectors [1,24,25,26]. This is largely because healthcare settings harbor a high density of pathogenic bacteria closely linked to human infections, which in turn creates a strong selective pressure from intensive antibiotic use [4,13,14]. Hospitals, clinics, and long-term care facilities represent concentrated environments where antimicrobial exposure, invasive medical procedures, and vulnerable patient populations converge, creating ideal conditions for the selection and transmission of resistant pathogens [13,14,15]. In contrast, sectors such as agriculture, aquaculture, and pharmaceutical manufacturing contribute to AMR mainly through environmental dissemination of antimicrobial residues and resistance genes, often involving commensal or environmental microorganisms rather than direct human pathogens [5,10,26,27,28]. While these sectors influence the broader ecological spread of resistance, healthcare facilities serve as immediate amplification hubs for multidrug-resistant organisms with direct implications for human health [4,16,17,19]. Therefore, controlling AMR within healthcare systems requires more stringent infection control measures, Antimicrobial Stewardship Programs (ASPs), and surveillance than those typically applied in environmental or agricultural contexts [13,14,32,33,34].

While AMR can originate from multiple sources, healthcare facilities are particularly susceptible due to the high concentrations of antibiotic use and presence of pathogenic bacteria, which contribute to environmental contamination. It is estimated that HAIs develop in approximately 15% to 37% of hospitalized patients in HICs [60]. The healthcare environment plays a critical role in HAIs transmission, as pathogens can spread between individuals and persist on contaminated surfaces [61]. Indeed, bacteria may survive on surfaces for up to four months, while viruses may survive for a few days [62]. Moreover, microorganisms can form biofilms, which provide protective barriers and facilitate horizontal gene transfer [63].

4.1. Surface Contamination

Surface contamination and inadequate hand hygiene are recognized as important factors contributing to the spread of AMR in healthcare facilities, as demonstrated by multiple studies reporting significant contamination across healthcare settings (Table 1) [64]. A study conducted in a hospital in Italy found that 33.6% of bacteria isolates from various surfaces were resistant to at least one antimicrobial [65]. The distribution was as follows: high-touch surfaces (40%; e.g., bed rails, food trays, door handles), floor (38%), air (10%), medical devices (9%), and healthcare workers’ hands (3%) [65]. Sinks and drains have also been implicated in AMR outbreaks, since they are susceptible to contamination (e.g., from body fluids), serve as reservoirs for persistent bacteria, and provide favorable conditions for the selection (e.g., from excreted antibiotics) and exchange of ARGs [66]. Indeed, 41% and 18% of sinks in a healthcare facility in Pakistan presented Enterobacteriaceae resistant to ertapenem and to the three classes of antibiotics tested (i.e., carbapenems, cephalosporins, and fluoroquinolones), respectively [67]. Bacteria can subsequently spread from these surfaces into patients. For instance, Klebsiella pneumoniae and Pseudomonas aeruginosa, previously found in a hospital wastewater network (e.g., toilets, sinks), were also identified in oncology patients, especially after 4 weeks of hospitalization [68].

While surface cleanliness can contribute to reducing the risk of infection [69], the use of chemical-based detergents and disinfectants may not produce adequate results in up to 50% of surfaces, surfaces might get re-contaminated within 30 min, and the use of these agents may select for resistant strains [64]. For instance, exposure to the antiseptic chlorhexidine has been associated with the selection of resistance to colistin in Klebsiella pneumoniae [70]. Conversely, a study in Italian hospitals during the COVID-19 pandemic reported that the increasing use of hand disinfectants led to a decrease in methicillin-resistant Staphylococcus aureus compared to previous periods [71]. Moreover, moving to a new hospital with private rooms led to similar counts of CFU after three years, but with a decrease from 3.3% to 0.1% in highly resistant strains [72].

4.2. Wastewater Contamination

Inadequately treated wastewater is a major source of resistant bacteria in natural ecosystems. While conventional wastewater treatment can reduce the abundance of ARGs (e.g., 2–4.5 log units gene copies/100 mL for tet genes), concentrations in effluents can remain high (up to 10⁶ gene copies/100 mL for total abundance of ARGs), thereby releasing them into the environment [73]. A study conducted in 62 wastewater treatment plants in the Netherlands reported ARGs discharge levels as high as 10⁶ copies/L, despite a decrease in ARGs by 1.76–2.65 log units during treatment [74]. Interestingly, the presence of discharge from healthcare facilities had only a marginal impact on ARGs concentration, most likely due to dilution (i.e., by representing only 1% of the untreated effluent). Conversely, a study in Belgium has found higher concentrations of ARGs in hospital wastewater and demonstrated increased levels of both antibiotic-resistant bacteria and ARGs downstream from the wastewater treatment plants’ discharge points [75]. This may be attributed to the presence of excreta from patients carrying resistant strains, which are more prevalent in clinical settings. However, Buelow et al. (2018) discovered that high levels of human-associated bacteria in hospital sewage did not significantly contribute to the number and variety of ARGs in the entire sewerage system [76]. The discrepancy between high levels of human-associated bacteria in hospital sewage and similar ARGs levels in WWTP effluent raises questions about the assumption that hospitals are the primary source of ARGs. The prompt dilution of hospital effluents in municipal wastewater could reduce their relative impact on AMR levels. The findings above demand an in-depth investigation of hospitals’ activities in shaping ARGs profiles in sewage systems. The presence of ARGs in untreated wastewater may also be useful for surveillance. A survey in Australia has found that the average length of hospital stays and presence of medium-sized residential aged care facilities explained one-third of the variation in extended-spectrum β-lactamases-producing Enterobacteriaceae in wastewater [77].

Beyond bacterial genes, antibiotics themselves may also exert selective pressures in the environment. Many antibiotics are excreted in active forms or as biologically active metabolites that are not fully removed by wastewater treatment processes. These compounds often reach the environment in sublethal concentrations capable of exerting selective pressures [78]. Antibiotics may persist in the environment depending on their organic carbon–water sorption coefficient (K_OC), since compounds with higher K_OC values have lower degradation rates [79]. For instance, tetracycline, excreted largely in its active form (>75%), persists in the aquatic environment (i.e., half-life of 34–329 h) [80] and has been found in concentrations of 0–20 ng/L in Europe [81]. Not surprisingly, resistance to tetracycline is one of the most common AMR found in domestic and wild animals [82,83,84]. The development of AMR can also be facilitated by the presence of other substances, such as biocides and heavy metals [85]. In addition to AMR development, antibiotics may also have ecological impacts on wild microorganism communities, as well as induce toxicity in other organisms (e.g., plants) [86].

4.3. Airborne Contamination

AMR may also be disseminated through indoor air in healthcare facilities, with recent studies demonstrating the impact of that pathway (Table 1). A concentration of 193 CFU/m³ was reported in indoor air in a hospital in China, with a predominance of Bacillus, Staphylococcus, Pseudomonas, and Micrococcus [87]. Besides the presence of opportunistic airborne pathogens that may cause nosocomial infections, high concentrations of ARGs were found in inpatient wards (104.46 copies/m³), which could result in an increased infection risk for both patients and medical staff [87]. Conversely, hospitals in Iran presented concentrations of airborne bacteria in the range of 99 to 1079 CFU/m³, with a prevalence of 30–40% of bacteria resistant to β-lactam antibiotics [88]. In another hospital, it was observed that 4.0–5.5% of ARGs in human airways were also present in inhalable particles, suggesting that they were shared [89].

Table 1. Comparative overview of healthcare facility–related AMR contamination by country, setting and type of contamination.

Country	Setting	Type of Contamination	Key Findings
Italy	Hospital surfaces	Surface contamination	33.6% of isolates resistant to ≥1 antimicrobial; high-touch surfaces and floors most contaminated [65]
Pakistan	Hospital sinks and drains	Surface/water network contamination	41% of sinks had Enterobacteriaceae resistant to ertapenem; 18% resistant to 3 antibiotic classes [67]
Italy	Hospitals	Surface contamination and infection control	Increased hand disinfectant use reduced MRSA prevalence [71]
Netherlands	Wastewater treatment plants	Wastewater contamination	ARGs discharge up to 106 copies/L; limited hospital effluent impact due to dilution [74]
Belgium	Hospital and downstream water	Wastewater contamination	Elevated ARGs and resistant bacteria downstream from hospital effluent [75]
Australia	Hospital wastewater survey	Wastewater contamination	Length of hospital stay and aged-care proximity correlated with ESBL-producing Enterobacteriaceae [77]
China	Hospital indoor and outdoor air	Airborne contamination	193 CFU/m3 in indoor air; ARGs 104.46 copies/m3 in inpatient wards; outdoor air near ventilation doubled ARGs abundance [87,90]
Iran	Hospital wards	Airborne contamination	99–1079 CFU/m3 airborne bacteria; 30–40% resistant to β-lactams [88]
Multiple (EUROPE)	Aquatic/soil environments	Antibiotic and chemical co-contamination	Tetracycline found in aquatic environments (0–20 ng/L); >75% excreted active [80,81,82]

Table 1. Comparative overview of healthcare facility–related AMR contamination by country, setting and type of contamination.

Country	Setting	Type of Contamination	Key Findings
Italy	Hospital surfaces	Surface contamination	33.6% of isolates resistant to ≥1 antimicrobial; high-touch surfaces and floors most contaminated [65]
Pakistan	Hospital sinks and drains	Surface/water network contamination	41% of sinks had Enterobacteriaceae resistant to ertapenem; 18% resistant to 3 antibiotic classes [67]
Italy	Hospitals	Surface contamination and infection control	Increased hand disinfectant use reduced MRSA prevalence [71]
Netherlands	Wastewater treatment plants	Wastewater contamination	ARGs discharge up to 106 copies/L; limited hospital effluent impact due to dilution [74]
Belgium	Hospital and downstream water	Wastewater contamination	Elevated ARGs and resistant bacteria downstream from hospital effluent [75]
Australia	Hospital wastewater survey	Wastewater contamination	Length of hospital stay and aged-care proximity correlated with ESBL-producing Enterobacteriaceae [77]
China	Hospital indoor and outdoor air	Airborne contamination	193 CFU/m3 in indoor air; ARGs 104.46 copies/m3 in inpatient wards; outdoor air near ventilation doubled ARGs abundance [87,90]
Iran	Hospital wards	Airborne contamination	99–1079 CFU/m3 airborne bacteria; 30–40% resistant to β-lactams [88]
Multiple (EUROPE)	Aquatic/soil environments	Antibiotic and chemical co-contamination	Tetracycline found in aquatic environments (0–20 ng/L); >75% excreted active [80,81,82]

Besides indoor air, healthcare facilities may also contaminate their surroundings. Outdoor air collected near the ventilation outfalls of a hospital in China showed a high influence of human commensal bacteria (e.g., Staphylococcus spp.) and presented twice the abundance of ARGs compared to the urban environment, with potential dissemination into the neighboring community [90]. Moreover, particulate matter <10 µm can act as a vector of bacteria containing ARGs and lead to their dissemination in the atmosphere [91].

4.4. Summary of the Contribution of Healthcare Facilities to AMR

Among the various contamination routes, surface contamination emerges as the most critical pathway for AMR transmission within healthcare environments [64]. High-touch surfaces, sinks, and drains act as persistent reservoirs of resistant microorganisms, enabling both direct patient exposure and horizontal gene transfer [64]. Conversely, while wastewater contamination represents a major vector for the environmental dissemination of ARGs, its direct contribution to intra-hospital transmission appears limited due to effluent dilution in municipal systems [74,77]. Airborne dissemination has also been reported but generally plays a secondary role, mostly under conditions of poor ventilation or high microbial load [87,88,89]. Overall, the persistence of resistant microorganisms on surfaces and their direct involvement in patient contact underscore surface contamination as the predominant route of AMR propagation in healthcare facilities.

5. One Health Perspective of the AMR in Healthcare

The natural environment functions both as a conduit and a reservoir for the spread of AMR, primarily by facilitating horizontal gene transfer among microbial populations [85]. This environmental reservoir of resistance genes poses a substantial risk of reintroduction into human and animal populations through various exposure pathways, including contaminated water sources, food consumption, and direct contact with contaminated environments. Antibiotics and resistant bacteria can be released into the environment from multiple sources (e.g., agricultural runoff, effluents) and transported over long distances, affecting ecosystems and potentially reaching human populations. These contaminants can impact ecosystems and eventually reach human populations through environmentally relevant sources, such as ambient air, drinking water, recreational water, and consumption of fresh produce. Notably, fresh vegetables are highly contaminated with AMR bacteria, with prevalence rates exceeding 50% [92]. In addition, animals can also contribute to the spread of AMR over long distances and through fecal contamination [93]. Once in the environment, resistance may persist depending on the fitness cost of carrying resistance genes, which influence their stability and maintenance within microbial communities [94]. While healthcare facilities can indirectly contribute to exposure through environmental contamination, the environment, in turn, may act as a persistent reservoir of ARGs, which can cycle back into healthcare settings through symptomatic and asymptomatic patients, reinforcing a bidirectional risk of exposure and transmission.

The healthcare environment is also a hotspot and source of AMR dissemination. As previously discussed, AMR may spread through high-contact surfaces and hands or contaminate natural environments mainly through the release of wastewater and ventilation outputs. Indeed, ARGs have been correlated with the presence of human-associated bacteria in the urban environment [95]. Moreover, the release of AMR into the environment by healthcare facilities may lead to the contamination of wildlife and domestic animals, which may contribute to its dissemination and, ultimately, to human exposure [96]. For instance, a high percentage of resistance to streptomycin (83%) and ampicillin (44%) was found in gull feces in Portugal, despite being characterized as critically important antibiotics for human medicine under European Union regulations and, therefore, having a restricted use [83]. However, the contribution of healthcare-associated environmental contamination to human and animal exposure to AMR remains understudied and requires further investigation.

The One Health Approach to combating AMR in healthcare facilities has paved the way for collaboration between the healthcare and environmental sectors. Integrated AMR management programs, such as Antibiotic Stewardship Programs, have demonstrated results-oriented teamwork. These collaborations bring together professionals from a variety of fields, including health, agriculture, veterinary medicine, and environmental sciences, to collaborate on AMR using the One Health approach. The goal is to carry out strategies to prevent and manage AMR in healthcare facilities. These efforts aim to establish rules and regulations for ensuring responsible antibiotic use, reducing prescription overuse, and limiting resistance. Wastewater surveillance pilots have emerged as an attractive approach for monitoring wastewater samples from healthcare facilities, metropolitan areas, and agricultural settings, providing crucial information about antibiotic resistance transmission pathways. These coordinated efforts show the effectiveness of comprehensive, interdisciplinary approaches to combatting antibiotic resistance and protecting public health across domains. Furthermore, initiatives such as cross-sectoral research collaborations, collaborative monitoring systems, and shared datasets can enhance the collaboration between the healthcare and environmental sectors. The cyclical and interconnected nature of these processes underscores the complexity of AMR dissemination and highlights the need for integrated multidisciplinary strategies. Considering the role of humans, animals, and the environment in the emergence and spread of resistance, a One Health approach is essential to provide systemic strategies and achieve maximal public health benefits with optimal resource use (Figure 3).

6. Dealing with AMR in the Healthcare Context

6.1. Future Outlook

All future projections indicate that AMR will pose an escalating global health burden, with mortality expected to rise 70% between 2022 and 2050, particularly in LMICs such as South Asia and Sub-Saharan Africa [2,6,18,19]. Total deaths will rise but age-standardized rates may fall (especially among children under five), with elderly mortality sharply increasing. These findings and trends highlight the challenges of future AMR issues and the need for urgent and sustained investments in advanced research, comprehensive policy interventions, and global collaboration [97].

The United Kingdom government predicted that, by 2050, AMR could cause up to 10 million deaths per year worldwide and result in a cumulative global economic loss of $100 trillion [6,22]. LMICs are expected to bear the brunt of this crisis, as the pace of bacterial resistance continues to outpace the development of new antibacterial agents. These countries often face severe resource limitations, making it difficult to access even existing high-cost antibiotics. Despite the global scale of the problem, international coordination is severely inadequate. Current containment efforts are fragmented and insufficient to keep pace with the prompt evolutionary adaptability of pathogenic microorganisms driven in large part by widespread and often indiscriminate antibiotic use across human healthcare, agriculture, and the environment [22].

Aside from immediate mortality and cost implications, the increasing ineffectiveness of antimicrobials has the potential to severely cripple modern healthcare systems. The loss of effective antibiotics could lead to the resurgence of previously rare or controlled bacterial infections. Cancer patients, immunocompromised individuals, and those requiring surgical treatments reflect populations more vulnerable to generating extensive or pan-drug-resistant bacterial strains [98]. Furthermore, the overall burden of common infectious diseases such as pneumonia, tuberculosis, and gastrointestinal infections is expected to rise dramatically in the post-antibiotic era. Finally, the rapid depletion of effective antibiotic alternatives threatens to undermine decades of medical progress and may force humanity back to an era in which bacterial infections posed one of the greatest threats to public health [6].

The future of AMR remains uncertain, and its growing threat poses significant risks to global health, food security, and economic stability. As previously mentioned, AMR is truly a One Health problem as it may disseminate in humans, animals, and the environment. Its impact on food production could hinder food security [47]. Impacts on food production could also cause disruptions in the world economy [99]. Just considering mastitis in dairy cattle, an increase in AMR could result in: (i) increased culling and replacement of animals; (ii) greater losses of milk due to reduced production and discarding due to antibiotic residues; (iii) increased costs with veterinary services and diagnostics; (iv) an elevated risk of regulatory fines due to antibiotic residues in milk [100]. Moreover, AMR may also develop in food production, namely when antibiotics are used in the prophylaxis and treatment of diseases in animals and plants. Considering only fluoroquinolone-resistant Campylobacter, the externalities of enrofloxacin use in chicken were estimated at US$1500 per kg of enrofloxacin used [101]. Waterbodies may also get contaminated with effluents, depending on existing wastewater treatments, and spread depending on environmental factors (e.g., temperature, volume) [102], which may be exacerbated by climate change. Therefore, animal production and the environment should also be considered when assessing the externalities of AMR originating from healthcare infrastructures.

In summary, AMR will increase the risk of medical procedures, decrease treatment options for common infections, challenge food security, and impact ecosystems. Surveillance should be strengthened, new antibiotics should be researched, and appropriate antibiotic use should be promoted to reduce its impact. Global collaboration and ingenuity will be critical in combating this emerging threat.

6.2. Challenges and Recommendations

6.2.1. Knowledge Gaps in Research

While our understanding of the AMR in the environment has improved, many critical questions remain unresolved. Although AMR has been reported in various habitats, including wastewater, hospital structures, and soil ecosystems, its sources and pathways remain unclear. Proper identification and assessment of the sources, transport routes, and exposure pathways will help quantify population transmission for better risk assessment and predictive modeling [103].

The dissemination of AMR outside healthcare facilities and its impact under a One Health perspective should also be prioritized. Given the significant contribution of agriculture, current farming and food production practices should be reevaluated to maintain productivity while preventing and managing AMR. Conducting localized studies on samples from healthcare environments (e.g., surfaces), natural environments (e.g., surface waters), wild and domesticated animals, and asymptomatic and symptomatic human populations can support the identification of circulating clusters of resistant bacteria.

Future research should also focus on improving existing Water, Sanitation, and Hygiene (WASH) and Infection Prevention and Control (IPC) infrastructures to mitigate AMR transmission within healthcare settings and beyond [104]. A critical step involves identifying and characterizing the specific sources and pathways of AMR in wastewater (Figure 4). Developing meaningful predicted no-effect concentrations (PNECs) for the development of AMR for various antimicrobials is critical to inform wastewater management.

In parallel, investment in the discovery and development of antimicrobials and alternative therapeutic strategies, such as bacteriophage therapy and monoclonal antibodies, is urgently needed. Notably, phage therapy has demonstrated efficacy against drug-resistant Acinetobacter baumannii infections [105], and monoclonal antibodies (e.g., bezlotoxumab) have been effective in treating antibiotic-resistant Clostridium difficile [106]. A truly integrated One Health approach will require coordinated efforts among microbiologists, pharmacologists, epidemiologists, environmental scientists, and policymakers. Furthermore, artificial intelligence holds great potential to support AMR data, facilitate risk modeling, and optimize treatment strategies using predictive analytics and data integration.

6.2.2. Surveillance and Healthcare

Although healthcare-associated infections are caused by a broad range of rare and common bacterial species (further divided into subspecies and strains with variable properties), a relatively small portion of these bacterial subtypes accounts for a significant majority of the AMR burden [13,107]. Pathogen monitoring is vital for preventing infections and controlling outbreaks [108]. However, routine diagnostics often identify pathogens only at the species level, which offers extremely low resolution for epidemiological tracking and no insight into resistance genetics [13]. Alternative methods based on ARGs, such as the use of metagenomics, might provide a broader perspective.

Monitoring the incidence of AMR allows healthcare practitioners to select effective antibiotics while minimizing the development and spread of resistant organisms [109]. ASPs in both human and veterinary healthcare facilities can aid in accurate antibiotic risk assessment. Antimicrobial stewardship has been proven effective in patient care by reducing misuse, such as overdosing, which leads to fewer infections, reduced AMR cases, optimized dosing for immunocompromised patients (e.g., those with renal impairment), improved cure rates, decreased mortality, and lower hospital costs [110]. Al-Omari et al. (2020) stressed the need for ASPs in reducing global ciprofloxacin resistance [111] and highlighted the success of ASPs in reducing C. difficile, ventilator-associated pneumonia, and central line-associated bloodstream infections, as well as in shorter antibiotic therapy durations, and less inappropriate antimicrobial use. In this study, ASPs at four healthcare facilities lowered broad-spectrum antibiotic use and expenditures. Advocating for the implementation of such initiatives in other contexts could improve patient safety and care.

Moreover, integrating tools like the GAP-ON€ platform to estimate direct AMR-related healthcare costs may support more informed policy and resource allocation [112]. However, existing AMR surveillance systems remain inadequate, with many LMICs facing implementation challenges due to a lack of resources and enforcement capacity [104,113]. Moreover, limited tools for detecting AMR in environmental samples hinder holistic AMR management efforts.

Preventing AMR spread also requires strict hygiene, sanitation, and disinfection practices within healthcare facilities. These interventions should address infrastructure-related hotspots, such as sinks and drains, and include environmentally sustainable solutions that limit the selection of resistant strains. Pretreatment of hospital effluents is particularly critical, as discharges may carry high ARGs loads. While conventional systems (e.g., activated sludge, membrane bioreactors) are costly, advanced disinfection technologies, such as UV radiation and ozonation, show promise for improved performance [114]. Moreover, surveillance of wastewater originating from healthcare might provide insights into the AMR status of the facility [115]. Additional measures include the isolation of infected patients, optimized ventilation systems, and prudent antibiotic use [88].

Surveillance must also extend beyond clinical settings. Recognizing the environmental and animal reservoirs of resistance, the European Union adopted Decision 2013/652/EU to harmonize AMR monitoring in food-producing animals, targeting Salmonella spp., Campylobacter jejuni, Campylobacter coli, Escherichia coli, and Enterococcus species. As part of the EU One Health Action Plan, monitoring of ARGs in surface and groundwater is also being implemented [116,117]. Similar One Health-integrated monitoring programs are urgently needed worldwide.

6.2.3. National Action Plans

AMR development substantially influences a country’s healthcare system and economy since it may result in additional costs and longer treatment or hospital stays [6,118]. Furthermore, AMR threatens agricultural productivity, food safety, and environmental sustainability. Success depends on governments, indigenous partners, and other sectoral stakeholders working together to tackle AMR. In LMICs, there is a lack of a national action plan for AMR. For example, in countries such as Pakistan, Nigeria, and Bangladesh, national AMR action plans have either not been developed or their implementation has been reported to be severely limited [119]. Populations in these regions often lack the resources to respond adequately to AMR and remain highly vulnerable to its consequences. To effectively combat AMR, a comprehensive and multidimensional strategy is required.

One Health strategy should prioritize global research, surveillance, and public health collaboration to address human and animal health implications of AMR [97]. The World Health Organization’s Global Action Plan on Antimicrobial Resistance, published in 2015, urges countries to develop their national plans aligned with this framework [120]. Strengthening surveillance is essential to track the emergence and spread of resistant illnesses. Data sharing among healthcare facilities, agricultural sectors, and research institutions should be encouraged to monitor resistance trends and guide public health interventions. Promoting responsible antimicrobial use through stewardship programs in healthcare settings can optimize antimicrobial use, ensuring they are prescribed only when necessary [6]. Similarly, stringent regulations on antibiotic use in agriculture and veterinary medicine are critical to reduce overuse. Such measures are particularly important for food producers engaged in export, to maintain access to international markets.

Adequate water and wastewater treatment infrastructures at the country level, as well as an advanced surveillance system, are necessary, particularly at sites receiving effluents from pharmaceutical companies and healthcare infrastructures. Investment in new technologies for reducing and treating contaminated waste and wastewater is critical to maintain human and environmental health.

Governments, pharmaceutical corporations, and research institutes should form collaborations to encourage creative antimicrobial development. Priority areas should include: (i) development and implementation of diagnostics and monitoring tools; (ii) preventive measures such as new drugs or vaccines; (iii) reduction in environmental release through adequate waste and wastewater treatment; (iv) implementation of effective cleaning and disinfection protocols in high-risk settings, such as healthcare facilities.

Finally, education plays a pivotal role in national AMR strategies. Public awareness campaigns should focus on the appropriate use of antibiotics, the negative consequences of overuse, the importance of following treatment plans, and the proper disposal of antibiotic residues [121]. Healthcare professionals should be regularly trained in infection control procedures and antimicrobial stewardship. Educational programs should generally be tailored to different target groups, from schools to community centers, to ensure broader and more effective awareness-raising on AMR.

A comparative overview of national AMR action plans, their implementation status, and key focus areas across selected countries is presented in Table 2. Countries were selected to represent a balance between high-, upper-middle-, and low- and middle- income regions to illustrate disparities in AMR policy adoption, implementation, and enforcement capacity. These differences highlight how financial, infrastructural, and governance factors directly influence national progress toward achieving One Health integration. As shown in Table 2, HICs generally demonstrate advanced and well-funded surveillance and stewardship frameworks, while LMICs continue to face limitations related to infrastructure, financing, and intersectoral coordination, underscoring the need for stronger international collaboration and equitable resource sharing.

Table 2. Comparative overview of national AMR action plans: adoption years, implementation status, and key focus areas.

Country/ Region	Year of NAP Adoption	Implementation Status	Key Focus Areas	Success Factors/Barriers	Reference(s)
High-Income Countries (HICs)
Australia	2015, updated 2020	Fully implemented	One Health stewardship, biosecurity	Success: strong veterinary linkage Barrier: limited rural coverage	[122]
Canada	2023 (Pan-Canadian Action Plan on AMR)	Adopted; early implementation	Research and innovation, surveillance, stewardship, IPC	Success: multi-jurisdictional alignment Barrier: provincial rollout variability	[123]
France	2022–2025 (National Strategy for Preventing Infections and AMR)	Implemented; human-health scope only	Awareness, education, research, monitoring	Success: integrated research and education programs Barriers: High antibiotic consumption; limited private sector data	[124]
Germany	1st Action Plan 2024–2026 2023 (DART 2030)	Adopted; rollout under 2024–2026 Action Plan	Prevention, surveillance, food chain, environment	Success: cross-ministerial coordination Barrier: federal-state implementation gap	[125]
Japan	2016	Fully implemented with regular reviews	Stewardship, surveillance, AMR education	Success: public engagement campaigns Barrier: fragmented healthcare sector	[126]
Netherlands	Dutch Action Plan for the reduction in AMR 2024–2030	In implementation; cross-ministerial; mid-term evaluation in 2027	One Health integration; EU/global coordination	Success: strong EU alignment, early surveillance network Barrier: resource allocation across provinces	[127]
Republic of Korea	1st NAP 2016–2020; 2nd 2021–2025	Implemented	Multisectoral surveillance (human, animal, food)	Success: data-driven approach Barrier: limited One Health integration	[128]
Sweden	1st NAP 2016–2020; 2nd 2020–2023; 3rd 2024–2025	Fully implemented	Cross-sector One Health data integration	Success: long-term continuity Barrier: minor EU data harmonization	[129]
Switzerland	StAR One Health Action Plan 2024–2027	Ongoing; revised under One Health framework	Prevention, stewardship, surveillance, environment	Success: long-term political commitment, inter-ministerial collaboration Barrier: limited environmental data integration	[130]
United Kingdom	2019 (5-year NAP; updated in 2024)	Fully implemented	Surveillance, stewardship, One Health, public awareness	Success: sustained funding and oversight Barrier: behavioral change in primary care	[131]
United States	2015, updated 2020	Broad implementation at federal/state level	Stewardship, surveillance, R&D	Success: robust research funding Barrier: uneven state policies	[132]
Upper-Middle-Income Countries
Brazil	2017	Implemented; cross-sector One Health initiative	Agriculture stewardship, livestock antibiotic regulations	Success: agriculture integration Barrier: limited rural surveillance	[133]
China	NAP 2022–2025	Recently adopted; ongoing	One Health integration; surveillance; rational use	Success: strong central coordination Barrier: regional variation	[134]
Turkey	2014–2017 (RDU NAP); updated via TrACSS 2021	Partially implemented; activities underway	Surveillance networks, stewardship, and multisectoral working groups	Success: intersectoral coordination Barrier: limited funding and formal approval	[135]
Low- and Middle-Income Countries (LMICs)
India	2017	Partial implementation; variable across states	Surveillance, stewardship, aquaculture antibiotic reduction	Success: growing research network Barrier: resource constraints	[136]
Kenya	1st NAP 2017–2022; 2nd NAP 2023–2027	Implemented	Multisectoral One Health AMR framework	Success: active One Health platform Barrier: limited laboratory capacity	[137]
Nigeria	2017 (NAP 1.0); 2024–2028 (NAP 2.0)	NAP 1.0 implemented limitations; NAP 2.0 under development	One Health governance; AMR surveillance; stewardship; operational planning and costing; monitoring and evaluation	Success: inclusion of M&E framework Barrier: structural funding gaps	[138,139]
Pakistan	2017	Partially implemented	Agriculture and food sector governance, awareness and practices	Success: updated multisectoral draft NAP Barrier: limited enforcement	[140]
Vietnam	2024–2025	Implementation ongoing; barriers remain	One Health coordination; surveillance; awareness	Success: regional training initiatives Barrier: limited financial resources	[141]

Note: The table is not exhaustive and reflects the latest available data from national action plans and governmental reports. AMR, antimicrobial resistance; NAP, National Action Plan; R&D, Research and Development; RDU, Rational Drug Use; TrACSS, Tool for the Assessment of Country Self-Assessment Capacities.

Table 2. Comparative overview of national AMR action plans: adoption years, implementation status, and key focus areas.

Country/ Region	Year of NAP Adoption	Implementation Status	Key Focus Areas	Success Factors/Barriers	Reference(s)
High-Income Countries (HICs)
Australia	2015, updated 2020	Fully implemented	One Health stewardship, biosecurity	Success: strong veterinary linkage Barrier: limited rural coverage	[122]
Canada	2023 (Pan-Canadian Action Plan on AMR)	Adopted; early implementation	Research and innovation, surveillance, stewardship, IPC	Success: multi-jurisdictional alignment Barrier: provincial rollout variability	[123]
France	2022–2025 (National Strategy for Preventing Infections and AMR)	Implemented; human-health scope only	Awareness, education, research, monitoring	Success: integrated research and education programs Barriers: High antibiotic consumption; limited private sector data	[124]
Germany	1st Action Plan 2024–2026 2023 (DART 2030)	Adopted; rollout under 2024–2026 Action Plan	Prevention, surveillance, food chain, environment	Success: cross-ministerial coordination Barrier: federal-state implementation gap	[125]
Japan	2016	Fully implemented with regular reviews	Stewardship, surveillance, AMR education	Success: public engagement campaigns Barrier: fragmented healthcare sector	[126]
Netherlands	Dutch Action Plan for the reduction in AMR 2024–2030	In implementation; cross-ministerial; mid-term evaluation in 2027	One Health integration; EU/global coordination	Success: strong EU alignment, early surveillance network Barrier: resource allocation across provinces	[127]
Republic of Korea	1st NAP 2016–2020; 2nd 2021–2025	Implemented	Multisectoral surveillance (human, animal, food)	Success: data-driven approach Barrier: limited One Health integration	[128]
Sweden	1st NAP 2016–2020; 2nd 2020–2023; 3rd 2024–2025	Fully implemented	Cross-sector One Health data integration	Success: long-term continuity Barrier: minor EU data harmonization	[129]
Switzerland	StAR One Health Action Plan 2024–2027	Ongoing; revised under One Health framework	Prevention, stewardship, surveillance, environment	Success: long-term political commitment, inter-ministerial collaboration Barrier: limited environmental data integration	[130]
United Kingdom	2019 (5-year NAP; updated in 2024)	Fully implemented	Surveillance, stewardship, One Health, public awareness	Success: sustained funding and oversight Barrier: behavioral change in primary care	[131]
United States	2015, updated 2020	Broad implementation at federal/state level	Stewardship, surveillance, R&D	Success: robust research funding Barrier: uneven state policies	[132]
Upper-Middle-Income Countries
Brazil	2017	Implemented; cross-sector One Health initiative	Agriculture stewardship, livestock antibiotic regulations	Success: agriculture integration Barrier: limited rural surveillance	[133]
China	NAP 2022–2025	Recently adopted; ongoing	One Health integration; surveillance; rational use	Success: strong central coordination Barrier: regional variation	[134]
Turkey	2014–2017 (RDU NAP); updated via TrACSS 2021	Partially implemented; activities underway	Surveillance networks, stewardship, and multisectoral working groups	Success: intersectoral coordination Barrier: limited funding and formal approval	[135]
Low- and Middle-Income Countries (LMICs)
India	2017	Partial implementation; variable across states	Surveillance, stewardship, aquaculture antibiotic reduction	Success: growing research network Barrier: resource constraints	[136]
Kenya	1st NAP 2017–2022; 2nd NAP 2023–2027	Implemented	Multisectoral One Health AMR framework	Success: active One Health platform Barrier: limited laboratory capacity	[137]
Nigeria	2017 (NAP 1.0); 2024–2028 (NAP 2.0)	NAP 1.0 implemented limitations; NAP 2.0 under development	One Health governance; AMR surveillance; stewardship; operational planning and costing; monitoring and evaluation	Success: inclusion of M&E framework Barrier: structural funding gaps	[138,139]
Pakistan	2017	Partially implemented	Agriculture and food sector governance, awareness and practices	Success: updated multisectoral draft NAP Barrier: limited enforcement	[140]
Vietnam	2024–2025	Implementation ongoing; barriers remain	One Health coordination; surveillance; awareness	Success: regional training initiatives Barrier: limited financial resources	[141]

Note: The table is not exhaustive and reflects the latest available data from national action plans and governmental reports. AMR, antimicrobial resistance; NAP, National Action Plan; R&D, Research and Development; RDU, Rational Drug Use; TrACSS, Tool for the Assessment of Country Self-Assessment Capacities.

6.2.4. International Cooperation

AMR can affect individuals globally, irrespective of geographical borders. The impact of international travel, with 30–70% of travelers returning with a more resistant gut flora, emphasizes the need for global action [142]. The consequences of AMR can be mitigated, but solutions require decisive, coordinated, and long-term action. AMR is a transboundary challenge, complicated by the lack of international consensus on the action plans and legislation. Governments, international organizations, and stakeholders must collaborate to harmonize regulations, exchange best practices, and coordinate responses effectively. The Global Action Plan on Antimicrobial Resistance, led by the WHO, aims to raise awareness and education among healthcare professionals and the public with a strong focus on surveillance, research, and evidence-based policymaking.

In LMICs, limited resources hinder effective monitoring and control of AMR [143]. Moreover, pharmaceutical corporations face low incentives to develop new drugs due to the increase in MDR microorganisms and costly trials, which limit profitability [6]. Therefore, limited access to diagnostics and appropriate antimicrobials requires novel approaches, including technological innovations. Since consequences are global, HICs may consider the benefit of sharing resources with LMICs and financing cost-effective technological solutions for surveillance and treatment of AMR.

The Global Antimicrobial Resistance and Use Surveillance System (GLASS), led by the WHO, demonstrates the value of standardized, collaborative data interchange that spans human health, the food chain, and environmental monitoring and improves global response [144]. Another initiative is the One Health Joint Plan of Action, a collaboration of the WHO, the Food and Agriculture Organization of the United Nations (FAO), the United Nations Environment Programme (UNEP), and the World Organization for Animal Health (WOAH) [145]. This five-year plan (2022–2026) intends to improve One Health efforts in dealing with complex problems, including AMR. In the context of these international initiatives, the specific challenges faced in healthcare settings and potential recommendations for addressing AMR are summarized in Figure 4.

Despite their initiatives, global coordination on AMR surveillance and stewardship remains fragmented. An effective global response requires an organized, equitable, and accountable governance framework, supported by sustainable financing (Figure 4). However, geopolitical challenges continue to preclude agreement on binding international regulations and resource allocation mechanisms [104,113].

7. Conclusions

AMR is a global challenge of increasing importance when considering direct and indirect impacts on society. Healthcare facilities act as convergence points, functioning both as contributors to and recipients of circulating AMR. They represent hotspots due to high antimicrobial use and the presence of susceptible populations. Resistant organisms may establish themselves and persist on high-touch surfaces and in the sanitation infrastructure. The intensive use of chemical-based cleaning and disinfectant agents contributes to AMR by creating selective pressures. Moreover, healthcare facilities might contribute to the contamination of the natural environment through the incomplete removal of organisms or ARGs in wastewater and ventilation outputs. The presence of AMR in the natural environment, either originating from healthcare or from other sources, such as the use of antibiotics in agriculture and animal production, may lead to human and animal exposure. The presence of AMR in the environment may also lead to human infection, which will be reintroduced in the healthcare system. Ultimately, AMR follows a complex cycle that requires additional research.

Current challenges include (i) the expected increase in AMR, that might be exacerbated by climate change and result in severe impacts on public health, food security, environmental health, and the economy; (ii) knowledge gaps, including a limited understanding of environmental cycles and need for cost-effective technologies; (iii) limitations in resources for technological advancements and implementation of measures in LMICs; (iv) active surveillance that covers all aspects of One Health; and (v) complementing national initiatives with international cooperation with accountability. Specifically in healthcare, essential measures to reduce AMR include improving antimicrobial stewardship, implementing local surveillance plans, improving cleaning and disinfection procedures, increasing awareness and education, and reducing environmental contamination. Ultimately, AMR is a One Health problem that can only be solved by a multidisciplinary approach. Healthcare facilities are one of the most important players in preventing and monitoring AMR, not only because they can greatly contribute to prevention, but also by keeping track of symptomatic cases. Strengthening AMR prevention and monitoring within healthcare settings must be accompanied by policy integration, measurable targets, and sustained investment in innovation to ensure long-term resilience.