The Convergence of Antibiotic Contamination, Resistance, and Climate Dynamics in Freshwater Ecosystems

Abstract

The convergence of antibiotic contamination, antimicrobial resistance (AMR), and climate dynamics poses a critical environmental and public health challenge. Freshwater ecosystems are increasingly threatened by the persistent presence of antibiotics, which, coupled with rising global temperatures, accelerate the development and spread of AMR. This review examines the sources, pathways, and mechanisms through which antibiotics enter freshwater systems and how climate change exacerbates these processes. This review discusses this convergence’s ecological and human health impacts, highlighting the implications for biodiversity and public health. It also explored the current monitoring and mitigation strategies, including advanced oxidation processes, natural-based solutions, and policy interventions. Finally, this review identifies critical research gaps and proposes future directions for managing the intertwined threats of antibiotic contamination, resistance, and climate change. It emphasizes the need for integrated, multidisciplinary approaches to protect freshwater resources in an increasingly volatile global environment.

1. Introduction

Freshwater ecosystems, encompassing rivers, lakes, and wetlands, are indispensable to the environment and human civilization. These systems provide drinking water, irrigation for agriculture, and habitats for many species. Still, they also play a crucial role in maintaining the balance of natural processes such as nutrient cycling and climate regulation [1]. Despite their importance, freshwater ecosystems are increasingly threatened by a convergence of factors, including antibiotic contamination, the spread of antimicrobial resistance (AMR), and the accelerating impacts of climate change [2,3,4]. This trifecta of challenges presents a complex and interlinked problem that requires urgent attention from scientists, policymakers, and the global community.

Antibiotic contamination has become a significant environmental issue over the past few decades. The widespread use of antibiotics in human medicine, agriculture, and aquaculture has led to contaminating water bodies with these potent compounds [3,5,6]. Antibiotics enter freshwater systems through various pathways, including wastewater discharge, agricultural runoff, and the improper disposal of pharmaceuticals. Once in the environment, these substances can profoundly affect microbial communities, leading to the selection of antibiotic-resistant bacteria (ARB) and the proliferation of antibiotic-resistance genes (ARGs). The persistence of antibiotics in aquatic ecosystems and their potential to disrupt aquatic ecology, promote antibiotic resistance (AMR), and pose risks to human health are significant concerns [7]. For instance, amoxicillin, one of the most used antibiotics in humans, showed elevated persistence in the environment, and even at low concentrations (7.80 ng/L), it exerted toxic effects on aquatic organisms [7,8,9].

The rise of AMR is one of our time’s most pressing public health challenges. The World Health Organization (WHO) has identified AMR as a global health threat that could undermine decades of medical progress [10]. Resistant bacteria can cause difficulty, if not impossibility, in treating infections, leading to higher mortality rates, prolonged hospital stays, and increased healthcare costs [11]. Antibiotics in the environment accelerate the spread of resistance, as bacteria in aquatic environments are exposed to sub-lethal concentrations of these drugs, providing a selective pressure for the emergence of resistant strains. The proliferation of AMR in aquatic environments is a critical concern, as resistant bacteria can disseminate through water systems, impacting human and animal health [11]. Elevated levels of ARB and ARGs have been observed in drinking water treatment and distribution systems, suggesting that water treatment and distribution may serve as important reservoirs for spreading antibiotic resistance [12]. Similarly, wastewater treatment plants and industrial facilities are significant sources of antibiotic contamination, as they can release these compounds into surface and groundwater [3,4]. Aquaculture systems, in particular, have been identified as “genetic hotspots” for transferring AMR due to the high diversity of bacteria and the prevalent use of antibiotics, probiotics, and other treatment regimens [13]. Agriculture, as well, can contribute to the introduction of antibiotics and the selection of ARB through runoff from concentrated animal feeding operations and manure disposal [7]. Introducing antimicrobial agents, detergents, disinfectants, and industrial pollutants, such as heavy metals, can further contribute to the evolution and spread of resistant organisms in aquatic environments [14]. Additionally, environmental bacteria can act as a vast reservoir of genes that can be converted into ARGs when they enter pathogenic organisms [14].

Climate change, another global crisis, is exacerbating the situation by altering freshwater ecosystems’ physical and chemical properties [13]. Rising temperatures, changing precipitation patterns, and more frequent extreme weather events are disrupting the balance of these ecosystems. These changes can influence the distribution and persistence of antibiotics in the environment, the dynamics of microbial communities, and the spread of AMR [13,14]. For example, higher temperatures can increase the metabolic rates of bacteria, potentially accelerating the transfer of resistance genes [13]. Similarly, changes in water flow can concentrate pollutants in certain areas, creating hotspots for resistance development.

The intersection of antibiotic contamination, AMR, and climate change creates a complex web of interactions that pose significant risks to freshwater ecosystems and human health. As these challenges are interconnected, addressing them requires a comprehensive approach that considers the environmental, biological, and social dimensions of the problem. This includes developing policies that reduce the release of antibiotics into the environment, improving wastewater treatment technologies, promoting responsible antibiotic use, and mitigating the impacts of climate change. This review aims to explore the convergence of these issues in detail, providing an overview of the current state of knowledge and identifying critical areas for future research. It does not focus on providing a detailed examination of antibiotic concentrations or ARG levels in freshwater systems, as their occurrence, distribution, sources, fate, and links to anthropogenic activities have already been extensively covered in the recent literature. Instead, the emphasis is on understanding the broader environmental and climatic factors influencing antibiotic contamination and the spread of AMR, which have received less attention [15,16,17,18,19]. By examining the sources and impacts of antibiotic contamination, the mechanisms driving the spread of AMR, and the role of climate change in shaping these dynamics, we can begin to understand the full scope of the problem and identify potential solutions. Through case studies and real-world examples, this article will also highlight the experiences of affected ecosystems and the lessons learned from efforts to mitigate these challenges.

2. Antibiotic Contamination in Freshwater

Antibiotic contamination has become a significant environmental concern, particularly in freshwater ecosystems. Human activities, including agricultural practices, pharmaceutical manufacturing, and improper disposal of unused or expired medications, primarily drive the proliferation of antibiotics in these environments. These contaminants can have far-reaching impacts on the health and stability of aquatic ecosystems, affecting not only the organisms living within these waters but also the quality of the water itself [3,5,6].

2.1. Sources and Pathways of Antibiotic Contaminants

The sources of antibiotic contamination in freshwater are diverse and often interrelated. Understanding these sources is critical to developing effective strategies for mitigating contamination and protecting aquatic ecosystems.

One of the primary sources of antibiotic contamination is agricultural runoff. Antibiotics are extensively used in livestock farming to prevent disease and promote growth. These drugs are often administered in large quantities, and animals excrete a significant portion without the drugs being metabolized [20]. As a result, antibiotic residues are present in animal waste and are frequently used as fertilizer on agricultural lands [21]. When it rains, these residues can be washed into nearby rivers, lakes, and streams, introducing antibiotics into the freshwater ecosystem [20]. Several studies have documented the presence of antibiotics in agricultural runoff and found that watersheds with intensive livestock farming had significantly higher antibiotic levels than areas with minimal agricultural activity [22,23,24,25,26]. This runoff introduces antibiotics into water bodies and contributes to the spread of ARB and ARGs in the environment [24,26]. Antibiotic residues in animal manure range from 1 to 136,000 μg/kg of dry matter [22]. These concentrations in animal waste are significantly higher than those typically found in municipal wastewater [4], exacerbating the issue of antibiotic contamination in aquatic environments. Tetracyclines, fluoroquinolones, and sulfonamides are frequently detected [23,24,26]. These antibiotics can persist in soil for extended periods, with some remaining detectable up to 7 months after manure application [27]. Composting can reduce antibiotic levels by 17–100%, with half-lives ranging from 1 to 105 days [22]. However, antibiotics can still leach into surface and groundwater, with relative mass losses of <5% [28]. In addition to contributing to the spread of AMR, antibiotics in manure pose ecological risks to corps and soil organisms [23,29].

Aquaculture, which involves farming fish and other aquatic organisms, has become a significant and growing source of antibiotic contamination in freshwater systems. In these operations, antibiotics are routinely used to prevent and treat infections and to promote growth under the often crowded conditions typical of fish farms [30]. However, these antibiotics do not remain contained only within the farmed environments, as they can enter surrounding ecosystems through multiple pathways, including uneaten medicated feed, fish manure, and the direct discharge of water treated with antibiotics [31]. Among the antibiotics commonly used in aquaculture, oxytetracycline has been particularly noted for its association with the emergence of ARB and the accumulation of residues in fish products intended for human consumption [32]. Studies have documented concentrations of oxytetracycline in aquaculture effluents ranging from 33 to 1626 ng/L [33]. Other antibiotics, such as oxolinic acid (41 to 1052 ng/L), amoxicillin (30 to 1145 ng/L), and florfenicol (21 to 1448 ng/L), have also been frequently detected in aquaculture effluents, highlighting the pervasive nature of antibiotic use in these operations [33]. The environmental impact of these practices is profound. Antibiotics from aquaculture can accumulate in the water and sediments of both fish farms and adjacent water bodies. This accumulation leads to elevated levels of antibiotic residues and fosters the development of ARB in these environments [33,34]. The widespread use of antibiotics in aquaculture, particularly in regions with intensive production like Southeast Asia, poses significant risks to both local ecosystems and broader environmental health. As resistant bacteria and resistance genes spread from aquaculture sites into natural waters, the complexity and scale of AMR increase, making it an even more formidable challenge to address.

Pharmaceutical manufacturing is another major contributor to antibiotic contamination. In many parts of the world, the improper disposal of waste from pharmaceutical factories has led to the contamination of nearby water bodies with high concentrations of antibiotics. These contaminants can devastate local ecosystems, especially in regions with weak regulatory oversight or enforcement. Studies have detected high concentrations of antibiotics in effluents from pharmaceutical plants, reaching up to 14 mg/L for ciprofloxacin [35]. These effluents can contain multiple antibiotic classes, including β-lactams, quinolones, macrolides, and sulfonamides [36]. The concentrations of antibiotics detected in the effluent from pharmaceutical manufacturers around Hanoi, Vietnam, were very high, with sulfamethoxazole reaching 252 μg/L, trimethoprim reaching 107 μg/L, ofloxacin reaching 85 μg/L, and ciprofloxacin reaching 41 μg/L. The study found that the concentrations of antibiotic residues in the effluent from pharmaceutical plants were higher than those from other sources, like hospitals and aquaculture farms [36]. This case highlights the need for stricter regulations and better waste management practices in the pharmaceutical industry to prevent such environmental contamination.

The improper disposal of unused or expired medications is a significant yet often overlooked source of antibiotic contamination. Many people are unaware of the environmental consequences of disposing of medications by flushing them down the toilet or throwing them in the trash. Once these drugs enter the sewage system, they can pass through wastewater treatment plants, often not equipped to remove pharmaceuticals effectively, and eventually make their way into rivers and lakes [3]. Educational campaigns and take-back programs have been introduced in some regions to address this issue, encouraging people to return unused medications to pharmacies or designated disposal sites. However, these initiatives are not yet widespread, and improper disposal remains a common practice in many areas, contributing to the ongoing problem of antibiotic contamination in freshwater ecosystems.

Urban wastewater and sewage are significant sources of antibiotic contamination in freshwater systems. Cities generate vast quantities of wastewater that contain human waste and a wide array of pharmaceuticals, including antibiotics. Wastewater treatment plants (WWTPs) are designed to remove many contaminants; however, they often fall short when eliminating pharmaceuticals, particularly antibiotics, from the treated effluent [3]. As reviewed by [37], the concentration of antibiotics in wastewater from sewage treatment plants can vary widely, ranging from low nanograms per liter to as high as 12.7 micrograms per liter. Antibiotics in WWTP effluents are influenced by several factors, including the types and quantities of antibiotics consumed by the urban population, the efficiency of the treatment processes used at the WWTPs, and the physicochemical properties of the antibiotics themselves [37]. For instance, antibiotics that are more resistant to degradation or have higher water solubility are more likely to persist through treatment. Additionally, the design and operational conditions of WWTPs—such as hydraulic retention time, temperature, and the presence of specific microbial communities—can significantly impact the extent to which antibiotics are removed during treatment. Research has consistently shown that antibiotics are frequently detected in the effluents of wastewater treatment plants, often at concentrations that can disrupt microbial communities in receiving waters and promote the development of ARB [37,38,39]. For example, a study conducted in Brazil found that several commonly used antibiotics were present in treated wastewater at levels that could contribute to the proliferation of ARB [3]. These findings underscore the urgent need for advancements in wastewater treatment technology, such as incorporating advanced oxidation processes, membrane filtration, or biological treatments specifically targeting pharmaceutical compounds, to effectively reduce the release of antibiotics into the environment and mitigate the associated risks.

2.2. Mechanisms of Antibiotic Contamination in Freshwater Systems

The persistence and behavior of antibiotics in freshwater environments are influenced by their chemical properties, such as solubility, hydrophobicity, and resistance to degradation. Many antibiotics are hydrophilic, meaning they readily dissolve in water, facilitating their transport through aquatic systems [40]. This property allows them to disperse widely, contaminating large areas of freshwater ecosystems. In contrast, more hydrophobic antibiotics are associated with sediments or organic matter, potentially leading to localized accumulation and long-term environmental presence [3,40].

Antibiotics exhibit varying degrees of persistence in the environment, with some compounds breaking down relatively quickly while others remain for extended periods [41]. Degradation processes include photodegradation, where sunlight breaks down the antibiotic molecules, and biodegradation, where microorganisms metabolize the compounds [41,42]. However, the rate at which these processes occur depends on several factors, including the chemical structure of the antibiotic, environmental conditions such as temperature and pH, and the presence of specific microorganisms capable of degrading the antibiotic. Some antibiotics, particularly those with more complex structures, may resist degradation, leading to prolonged environmental contamination and increased potential for ecological impacts [41].

Moreover, antibiotics can bioaccumulate in aquatic organisms, leading to higher concentrations in their tissues than in the surrounding water [43,44]. This bioaccumulation can occur through direct exposure to contaminated water or indirectly through the food chain, where organisms consume other contaminated species. Persistent antibiotics that bioaccumulate in aquatic organisms can significantly impact higher trophic levels, including fish and humans who consume contaminated seafood. The accumulation of antibiotics in aquatic organisms raises concerns about ecological health and human exposure to these compounds by consuming aquatic products, potentially contributing to AMR and other health risks [45].

2.3. Impact of Antibiotics on Freshwater Ecosystems

Introducing antibiotics into freshwater ecosystems can have many adverse effects, many of which are still not fully understood. These impacts extend beyond the immediate toxicity to aquatic organisms and encompass broader ecological and evolutionary consequences that threaten the stability and health of these environments.

One of the primary concerns is the disruption of microbial communities, which play a crucial role in maintaining the overall functioning of freshwater ecosystems. Microorganisms such as cyanobacteria and ammonium-oxidizing bacteria are particularly susceptible to antibiotic exposure [46,47]. These microorganisms are integral to processes like nutrient cycling, the decomposition of organic matter, and the breakdown of contaminants. However, when antibiotics enter the environment, they can selectively kill susceptible bacteria, increasing resistance strains’ proliferation [48]. This selective pressure not only diminishes microbial diversity but also destabilizes the ecosystem. For instance, studies have shown that the presence of antibiotics can significantly reduce the abundance of bacteria involved in nitrogen cycling, leading to the accumulation of harmful nitrogen compounds in the water [49]. Such alterations can cascade through the ecosystem, affecting microorganisms, plants, and animals that rely on these processes for survival.

A particularly alarming impact of antibiotic contamination is the selection of ARB. When bacteria in freshwater environments are exposed to sub-lethal concentrations of antibiotics, those with resistance traits are more likely to survive, reproduce, and pass on these traits [48]. Over time, this can lead to the emergence and spread of resistant strains, posing a severe threat to environmental and human health. Freshwater ecosystems, especially those already burdened by contamination, can act as reservoirs and conduits for spreading antibiotic resistance [48]. Rivers and streams, for example, can transport resistant bacteria and resistance genes over long distances, spreading these traits across various environments [3]. This spread complicates efforts to manage antibiotic resistance and heightens the risk of resistant bacteria entering human populations through contaminated water.

In addition to disrupting microbial communities and fostering resistance, antibiotics can be directly toxic to many aquatic organisms. The level of toxicity varies depending on the species and the specific antibiotic compound, but even environmentally relevant concentrations can have detrimental effects [8,50]. For example, antibiotics can cause genotoxicity, histopathological changes, and alterations in fish’s developmental, cardiovascular, and metabolic systems [51,52,53]. At the community level, antibiotics can disrupt interspecific interactions and alter the structure and function of planktonic ecosystems [54]. Exposure to certain antibiotics has been shown to impair the growth and reproduction of aquatic invertebrates, while others can disrupt photosynthesis, leading to reduced primary production in aquatic ecosystems [6,45,55,56,57]. These biological disruptions can ripple through the food web, ultimately impacting the ecosystem.

The combined effects of antibiotic contamination—disruption of microbial communities, selection for resistant bacteria, and direct toxicity to aquatic organisms—can lead to profound changes in the functioning of freshwater ecosystems. These changes include altered nutrient cycling, reduced decomposition rates, and shifts in species composition. For example, the loss of critical microbial species involved in organic matter decomposition can slow the breakdown of organic materials, leading to the accumulation of residues in water bodies. This accumulation can reduce oxygen levels, create dead zones, and make the environment less hospitable for aquatic life. Moreover, the spread of resistant bacteria can change the competitive dynamics among microbial species [48], potentially leading to the dominance of resistant strains with different ecological roles, further altering the ecosystem’s balance and resilience.

In conclusion, antibiotics in freshwater systems represent a multifaceted threat that impacts ecosystem health on both micro and macro scales. Addressing these challenges requires a comprehensive understanding of how antibiotics interact with and alter these environments and a concerted effort to mitigate their presence in our water bodies.

3. Antibiotic Resistance Development and Dissemination

Antimicrobial resistance is a growing global concern, particularly in freshwater environments where antibiotics and other antimicrobials can accelerate the development and spread of resistant microorganisms. The mechanisms by which resistance emerges and disseminates are complex, involving genetic changes in microbial populations and the movement of resistance genes across different environments. Understanding these processes is essential for addressing the challenges posed by AMR in both ecological and human health contexts.

3.1. Mechanisms of Resistance in Microbial Populations

Microbial populations can develop antibiotic resistance through several mechanisms, including mutation, horizontal gene transfer (HGT), and selective pressure from exposure to sub-lethal concentrations of these drugs [58]. Mutations in bacterial DNA can occur spontaneously, and if they confer a survival advantage in the presence of antibiotics, these traits can rapidly spread through a population [59]. HGT is another crucial mechanism in the development of AMR. This process allows bacteria to acquire resistance genes from other bacteria, often by transferring mobile genetic elements such as plasmids, transposons, and integrons [60]. These genetic elements can move between bacterial species and even across different environments, facilitating the widespread dissemination of resistance traits [58]. The ability of bacteria to share resistance genes through HGT is a significant factor in the rapid spread of AMR across diverse ecological niches.

Selective pressure from exposure to sub-lethal concentrations of antibiotics further drives the development of resistance. When bacteria are exposed to low levels of antibiotics, those with resistant traits are more likely to survive and reproduce, gradually leading to a population dominated by resistant strains [59]. This phenomenon is particularly concerning in aquatic environments, where antibiotics often persist at sub-lethal concentrations, creating ideal conditions for selecting and amplifying resistance.

3.2. Horizontal Gene Transfer in Aquatic Environments

HGT is crucial in disseminating AMR within aquatic environments [58]. Water bodies such as rivers, lakes, and estuaries act as reservoirs and conduits for resistance genes, enabling the transfer of these genes between environmental bacteria and pathogenic microorganisms. This gene exchange complicates efforts to control AMR’s spread, increasing resistance traits across different microbial communities.

Several factors enhance the potential for HGT in aquatic systems, with biofilms and bacteriophages being particularly influential [61]. Biofilms, structured communities of bacteria embedded in a self-produced extracellular matrix, provide a protective and stable environment where bacteria can survive and thrive, even under adverse conditions. Within these biofilms, the proximity of bacterial cells facilitates the exchange of genetic material, including resistance genes [61]. Biofilms are hotspots for HGT, where traditional mechanisms such as conjugation, transformation, and transduction occur more frequently. In addition to these established methods, membrane vesicles have emerged as a novel mechanism for gene transfer within biofilms [61]. The biofilm matrix offers protection against environmental stresses, such as antibiotic exposure, enabling resistant bacteria to persist and spread more effectively.

Bacteriophages, viruses that infect bacteria, also significantly mediate gene transfer between bacterial species. These viruses can carry resistance genes from one bacterium to another, further contributing to the spread of AMR in aquatic environments [62]. The interaction between biofilms and bacteriophages creates a highly dynamic environment where resistance genes can be exchanged and disseminated rapidly. This rapid dissemination poses substantial challenges for managing AMR in freshwater ecosystems, as it increases the likelihood of resistance traits spreading beyond local microbial populations and entering broader ecological networks.

The combined effects of biofilms and bacteriophages in facilitating HGT highlight the complexity of controlling AMR in aquatic environments. These factors underscore the need for comprehensive strategies that address the various pathways through which resistance genes are transferred and spread. Such strategies could include the development of targeted interventions to disrupt biofilm formation or limit the activity of bacteriophages alongside broader efforts to reduce the presence of antibiotics and other stressors that drive the selection of resistant bacteria in these ecosystems.

3.3. Role of Biofilms in Protecting Resistant Bacteria

Biofilms are pivotal in the persistence and dissemination of antibiotic-resistant bacteria in aquatic environments. These microbial communities can form on various surfaces, including natural substrates, like sediments and plant roots, and artificial structures, like pipes and water treatment facilities. The resilience of biofilms is a critical factor in their ability to protect bacteria from a wide range of environmental stresses [63]. The extracellular matrix enveloping biofilms is a formidable physical barrier, effectively shielding the bacteria from antibiotics and other antimicrobial agents. This protective layer allows resistant bacteria to survive in conditions typically lethal to free-floating or planktonic bacteria [64].

The protection afforded by biofilms enhances antibiotic resistance through several mechanisms. First, the biofilm’s dense structure restricts antibiotics’ penetration, preventing them from reaching and effectively killing the bacteria inside. Second, bacteria within biofilms often exhibit altered growth rates, which can reduce the efficacy of antibiotics that target actively dividing cells. Third, the proximity of bacterial cells within biofilms facilitates HGT, a process crucial for the exchange and spread of resistance genes [65,66]. These factors collectively contribute to the enhanced resistance observed in biofilm-associated bacteria. The extracellular matrix of biofilms, rich in exopolysaccharides, plays a crucial role in biofilm formation and the maintenance of antibiotic resistance. Exopolysaccharides help to establish the biofilm’s structural integrity and regulate its internal environment. Quorum sensing, a form of bacterial communication, and efflux pumps, which expel toxic substances from bacterial cells, are two fundamental mechanisms that operate within biofilms to manage stress and enhance survival under antibiotic pressure [67]. The improved resistance of biofilm-embedded bacteria compared to their planktonic counterparts is well-documented and is a significant factor contributing to chronic infections that are difficult to treat [68].

Biofilms are not confined to natural environments; they are also prevalent on surfaces in human-made environments, such as water distribution systems and wastewater treatment facilities. The biofilms in these systems complicate efforts to control the spread of AMR. Biofilms provide a reservoir of resistant bacteria that are difficult to eliminate and can persist even in treated water systems. This persistence poses significant challenges for public health, as biofilms can serve as a continuous source of resistant bacteria that may be released into the environment or water supply. Understanding the role of biofilms in protecting and spreading resistant bacteria is critical for developing effective strategies to combat AMR in aquatic environments. Targeted approaches that disrupt biofilm formation, enhance antibiotic penetration, or inhibit quorum sensing could be pivotal in reducing the resilience of biofilm-associated bacteria. Moreover, addressing biofilm-related challenges in water treatment and distribution systems is essential to limit the spread of resistance and protect both environmental and human health.

3.4. Regional and Environmental Factors Influencing AMR Development

A complex interplay of regional and environmental factors shapes the development and spread of AMR in freshwater systems. These factors include local practices, infrastructure, climate, and regulatory frameworks, which collectively determine how antibiotics are introduced into the environment, persist in ecosystems, and impact global aquatic life and human health.

One of the primary contributors to AMR development is the overuse of antibiotics in healthcare, agriculture, and veterinary settings [69]. In regions where antibiotics are heavily relied upon in these sectors, the environmental burden of these compounds increases, leading to higher levels of contamination in soil, water, and air. These environmental reservoirs become critical sites for disseminating antibiotic-resistant bacteria and resistance genes, further complicating efforts to control AMR [70]. Specific regional factors can also exacerbate the spread of AMR. For example, rapid population growth, international migration, and inadequate wastewater treatment infrastructure can amplify the challenges of managing antibiotic contamination [71]. In areas with high population density, the demand for healthcare and agricultural products increases, often leading to intensified antibiotic use. When combined with poor waste management practices, these factors result in the persistence of antibiotics in the environment, creating ideal conditions for developing and spreading resistance.

Environmental conditions also play a critical role in influencing AMR development. Abiotic stresses, such as soil salinity and contaminants, can impact the behavior of antibiotic-resistant bacteria in agricultural soils [72]. Additionally, the presence of natural products and environmental conditions, including heavy metals and oxidative stress, can further influence the development of resistance [73]. These factors can create environments where bacteria with resistance traits are more likely to survive and proliferate, contributing to the broader spread of AMR. Climate is another significant factor influencing antibiotics’ fate and AMR’s spread [13]. Tropical regions characterized by high temperatures and heavy rainfall may experience more rapid degradation of certain antibiotics due to increased microbial activity and enhanced photodegradation under intense sunlight. However, these same regions are also more susceptible to higher runoff rates during heavy rainfall events, which can transport large quantities of antibiotics into freshwater systems. This runoff can lead to contamination spikes that challenge the resilience of local ecosystems. Conversely, temperate regions may see a prolonged persistence of antibiotics during colder periods, as lower temperatures can slow down microbial activity and the degradation of contaminants. These regions might also face sudden increases in antibiotic levels during heavy rainfall, as the runoff from agricultural lands and urban areas introduces significant quantities of antibiotics into water bodies [3]. The variations in climate across different regions highlight the need for tailored strategies that consider the specific environmental conditions affecting antibiotic contamination and the development of AMR.

The extent of antibiotic contamination and the prevalence of AMR can vary significantly between regions, depending on local practices and environmental factors. In countries where the use of antibiotics in agriculture is prevalent, such as in large-scale livestock farming, water bodies often show higher levels of antibiotic contamination. The widespread application of antibiotics in these regions, coupled with inadequate waste management practices, leads to the persistence of these compounds in the environment, promoting the development of resistance [74]. In contrast, regions with stricter regulations on antibiotic use may experience lower levels of contamination. However, even in these areas, densely populated or industrialized regions remain vulnerable to contamination due to the concentration of human activities and the inherent challenges of managing large-scale wastewater treatment systems [71].

In summary, a wide range of regional and environmental factors influence the spread of AMR in freshwater systems. Understanding these influences is crucial for developing effective, region-specific strategies to combat antibiotic contamination and the proliferation of resistance. Whether through stricter regulations, improved waste management practices, or climate-adapted approaches, addressing the multifaceted nature of AMR requires coordinated efforts that consider the unique challenges and opportunities presented by different environmental and regional contexts.

3.5. AMR and Its Detrimental Effects

Antibiotic contamination’s ecological and human health impacts on freshwater systems are profound and multifaceted [75]. Even at sub-lethal concentrations, antibiotics can substantially disrupt microbial communities that play critical roles in the decomposition of organic matter and nutrient cycling [47] and impact aquatic invertebrates [4,76], leading to population declines and reduced biodiversity. Such losses in biodiversity and changes in ecosystem functioning undermine the resilience of freshwater systems to environmental stressors, threatening their long-term sustainability.

Human health is directly impacted by exposure to antibiotic contaminants through various pathways, including drinking water, recreational activities, and consuming contaminated seafood. The presence of antibiotics in drinking water can pose significant health risks, especially to vulnerable populations, such as infants, older adults, and individuals with compromised immune systems. Additionally, consuming fish and other aquatic organisms with bioaccumulated antibiotics can expose humans to low levels of these drugs over time, potentially contributing to the development of AMR [45,77]. The spread of resistant bacteria and genes through contaminated water systems further complicates efforts to protect public health. This spread increases the prevalence of resistant infections, which are more challenging to treat and lead to higher morbidity and mortality rates.

The economic and social implications of AMR are equally alarming. Resistant infections result in more extended hospital stays, higher medical costs, and increased mortality, significantly burdening healthcare systems worldwide [78]. In the agricultural sector, AMR diminishes the effectiveness of veterinary treatments, impacting animal health and productivity. This reduction in productivity leads to economic losses for farmers and higher costs for consumers [11]. Beyond these direct financial impacts, AMR also affects broader societal well-being, reducing the quality of life, causing loss of income, and placing increased pressure on public health systems. The spread of AMR poses additional challenges for global trade and food security, as countries may impose restrictions on importing and exporting products from regions with high levels of antibiotic contamination [29,79]. Addressing AMR’s economic and social challenges requires coordinated action at local, national, and international levels. Efforts must focus on reducing antibiotic contamination in the environment and preventing the spread of resistance. This includes implementing stricter regulations on antibiotic use, improving waste management practices, and promoting public awareness of the risks associated with antibiotic misuse.

In conclusion, the development and dissemination of AMR in freshwater systems are shaped by a complex interplay of regional, environmental, and socio-economic factors. These factors determine the extent of antibiotic contamination and the spread of resistance and influence AMR’s broader ecological and human health impacts. Addressing the challenges AMR poses requires a comprehensive and multifaceted approach that considers the specific conditions and practices of different regions while recognizing the global nature of the problem. Effective management strategies must be adaptable, context-specific, and coordinated across multiple scales to mitigate the growing threat of AMR.

4. Climate Change and Its Impact on Freshwater Ecosystems

Climate change is one of our most significant environmental challenges, with profound and far-reaching impacts on freshwater ecosystems. As global temperatures rise and weather patterns become increasingly erratic, the delicate balance of these ecosystems is disrupted. This disruption exacerbates existing environmental pressures, such as antibiotic contamination, and introduces new threats. Understanding how climate change influences freshwater systems is crucial for developing strategies to protect these vital resources and the myriad species that depend on them.

4.1. Temperature Shifts and Water Chemistry and Flow

One of the most direct effects of climate change on freshwater ecosystems is the increase in water temperatures. By the end of the 21st century, under a moderate scenario of greenhouse gas emissions, global surface temperatures are projected to rise by 2 to 4 °C, with some predictions indicating an increase of up to 5.7 °C [80]. Warmer water temperatures can have various biological and chemical consequences, many detrimental to aquatic life. For instance, higher temperatures can accelerate the metabolism of aquatic organisms, leading to increased oxygen consumption and heightened stress levels in species already vulnerable to environmental changes [81,82]. Additionally, warmer temperatures reduce oxygen solubility in water, leading to hypoxic conditions that can harm fish and other aquatic organisms [83]. The increased evaporation rates associated with higher temperatures can also lead to water salinization, imposing osmotic stress on aquatic organisms and disrupting ion balance and water uptake mechanisms [84].

In addition to temperature shifts, changes in pH levels are another critical aspect of water chemistry that can be influenced by climate change [85]. Climate-driven alterations in precipitation patterns and increased atmospheric CO₂ levels can lead to the acidification or alkalinization of freshwater bodies. Shifts in pH can significantly impact aquatic ecosystems’ overall health by influencing organisms’ physiological processes [86]. Many aquatic species are susceptible to changes in pH, and deviations from their optimal pH range can lead to stress, reduced reproductive success, and increased mortality [86]. These stressors can compound the effects of other environmental changes, such as temperature increases, further threatening the resilience of freshwater ecosystems.

Climate change also alters the hydrological cycles that govern water flow and distribution in freshwater ecosystems. Changes in precipitation patterns, including the increased frequency of extreme rainfall events and prolonged droughts, can significantly impact the quantity and quality of water in rivers, lakes, and wetlands. Fluctuating water levels can lead to drought and flooding, presenting unique challenges for the survival of aquatic organisms. Additionally, rising sea levels associated with global warming may contribute to the salinization of freshwater environments, imposing salinity stress on organisms not adapted to such conditions [87].

As discussed in Section 5, climate change may also impact water quality by altering the behavior and persistence of contaminants, including antibiotics. Changes in the bioavailability of these contaminants will directly affect water quality and toxicity to aquatic organisms [88].

4.2. Impacts of Climate Change on Aquatic Life

The combined effects of rising temperatures and altered water flow have profound implications for aquatic life. Species adapted to specific temperature ranges or flow conditions may struggle to survive as these parameters shift. For instance, cold-water fish species, such as trout and salmon, are particularly vulnerable to warming waters. These species may experience reduced reproductive success, altered migration patterns, and increased mortality rates as temperatures rise [89]. Additionally, climate change may alter the distribution and prevalence of aquatic species, favoring those with greater tolerance to increasing temperatures. This shift can lead to significant changes in species composition within ecosystems, potentially disrupting established ecological relationships and balance [90].

Climate change also affects the timing and intensity of critical biological processes such as breeding, feeding, and migration [91,92]. These disruptions can create mismatches between the availability of resources and the needs of species, further stressing populations and reducing biodiversity [91]. For example, if temperature changes cause certain species to breed earlier in the year, the availability of food resources that are typically synchronized with breeding cycles might no longer align, leading to reduced survival rates of offspring and overall population declines. Beyond individual species, climate change significantly impacts entire freshwater ecosystems through alterations in water quantity, quality, and timing [93]. These changes affect aquatic environments’ physical, chemical, and biological characteristics [94]. As a result, ecosystems may experience shifts in species distributions, altered food web dynamics, and changes in overall ecosystem functioning [95]. Global-scale analyses suggest climate change will likely modify river flow regimes more extensively than current anthropogenic impacts, which could have far-reaching consequences for freshwater resources, especially in regions already under stress [96,97].

The impacts of climate change on freshwater ecosystems are not uniform and can vary widely across different regions. For instance, changes in lake mixing regimes, nutrient loading, and habitat availability are expected to differ based on local climatic conditions, land use, and species composition [98]. These regional variations necessitate proactive assessment and monitoring to effectively manage and mitigate the impacts of climate change on freshwater resources. Furthermore, climate-induced changes must be considered alongside other anthropogenic stressors, such as land-use alterations and species invasions, which can exacerbate the effects of climate change and complicate management efforts [98]. Understanding these complex interactions is crucial for developing effective management strategies and mitigation measures that address the multifaceted nature of climate change’s impact on freshwater ecosystems [99]. For example, the combined pressures of climate change and antibiotic contamination can create a feedback loop where stressed organisms become more susceptible to disease and the impacts of contaminants. In turn, changes in species composition can alter ecosystem dynamics in ways that exacerbate the effects of climate change, leading to further instability in these ecosystems.

In conclusion, the impact of climate change on freshwater ecosystems is multifaceted and deeply interconnected with other environmental pressures. Rising temperatures, changes in water chemistry, and altered flow patterns contribute to significant challenges for aquatic species and ecosystems. Addressing these challenges requires a comprehensive understanding of how climate change interacts with existing threats, such as contamination, to develop effective strategies for preserving freshwater resources and the biodiversity they support. This integrated approach is essential for ensuring the resilience and sustainability of freshwater ecosystems in the face of ongoing and future climatic changes.

5. Intersection of Antibiotic Contamination and Climate Change

Climate change is increasingly recognized as a critical factor influencing the contamination of freshwater ecosystems, particularly with respect to antibiotics. The interplay between rising global temperatures, altered precipitation patterns, and extreme weather events can significantly affect antibiotics’ behavior, distribution, and impact in these environments. This section explores how these climatic changes are expected to influence AMR and the health of antibiotic-contaminated freshwater ecosystems.

5.1. Increased Temperatures and Their Effect on Antibiotic Activity

As global temperatures rise due to climate change, the behavior and fate of antibiotics in freshwater systems are expected to change in complex ways (Figure 1). Higher temperatures can accelerate the degradation of certain antibiotics, potentially reducing their persistence in the environment [100]. For instance, warmer conditions can lead to faster photodegradation or chemical breakdown of some antibiotics [101]. Additionally, temperature influences antibiotic hydrolysis rates, with a 10 °C increase leading to 2.5–3.9-fold faster degradation [102]. As a result, lower concentrations of these antibiotics might be expected in the water. However, this degradation process is not uniform across all antibiotic types. Some compounds may become more stable or active at higher temperatures, prolonging their environmental presence and increasing their potential to cause harm [103]. Moreover, the breakdown products of antibiotics that degrade under higher temperatures are not always less toxic. In some cases, these degradation byproducts can be more harmful or persistent than the original compound, posing new risks to aquatic ecosystems [104].

In addition to influencing the persistence of antibiotics, increased temperatures can significantly impact aquatic microorganisms’ metabolic rates and resistance mechanisms. Higher temperatures generally enhance antimicrobial activity within a specific physiological range (35–41.5 °C), with some antibiotics showing up to 16-fold increased potency [105]. However, this effect can vary significantly depending on the antibiotic class, bacterial species, and the organisms’ temperature adaptations [105] and typically does not outweigh the overall favorable effects of rising temperatures in promoting AMR. Notably, rising environmental temperatures have been linked to increased antibiotic resistance in common pathogens, with a 10 °C increase associated with a 2.2–4.2% higher resistance rate [106]. Similarly, a 1 °C increase in average ambient temperature from 2005 to 2019 was associated with a 1.14-fold increase in Klebsiella pneumoniae (CRKP) and a 1.06-fold increase in CRPA prevalence [107]. Warmer waters can accelerate the growth and activity of bacteria, including those carrying ARGs. This can lead to a more rapid development and spread of AMR in freshwater ecosystems. Furthermore, higher temperatures may enhance HGT between bacteria, facilitating the spread of resistance traits [108]. Warmer conditions can also increase the abundance of naturally occurring ARGs in river biofilms [109].

Climate change can also alter the pH and salinity of water bodies, further influencing the degradation and bioavailability of antibiotics. Changes in pH, for instance, can affect the chemical stability of antibiotics, altering their breakdown rates and the toxicity of their byproducts [110]. Similarly, increased salinity due to rising sea levels or changes in freshwater input can affect the solubility and distribution of antibiotics [111], impacting their persistence and ecological impact. The combined effects of increased temperature on antibiotic persistence and microbial dynamics present a significant challenge for managing antibiotic contamination in a warming world. These findings suggest that climate change could exacerbate the antibiotic resistance crisis, making it more difficult to control the spread of resistant bacteria and the genes they carry [112]. Freshwater environments act as reactors for the evolution and spread of AMR, facilitating genetic exchanges between environmental and allochthonous species [113]. The compounding effects of climate warming and AMR underscore the need for a multidisciplinary approach to address this growing public health threat. The overall impact of temperature on bacterial growth and antibiotic efficacy is complex. It can vary between species and drug–organism combinations, highlighting the importance of continued research to inform effective mitigation strategies.

5.2. Changes in Precipitation Patterns and Runoff

Climate change is projected to cause significant alterations in precipitation patterns, with some regions experiencing more intense and frequent rainfall, while others may face prolonged periods of drought [80]. These changes in precipitation can profoundly affect the transport and concentration of antibiotics in freshwater systems [3].

Increased rainfall and extreme weather can lead to higher runoff from agricultural fields, urban areas, and industrial sites [114]. This runoff often contains elevated antibiotics used in agriculture and human medicine, which are transported into rivers, lakes, and streams [115]. The sudden influx of antibiotics during heavy rainfall can overwhelm the natural capacity of freshwater systems to dilute and degrade these contaminants, leading to acute contamination events that can harm aquatic life. Conversely, regions experiencing prolonged droughts may face different challenges. Reduced water flow during drought conditions can concentrate contaminants, including antibiotics, in smaller volumes of water. This can increase the exposure of aquatic organisms to higher concentrations of antibiotics, exacerbating their toxic effects and promoting the selection of resistant bacteria. The dual impacts of increased runoff and concentrated contaminants highlight the need for adaptive management strategies that can respond to varying precipitation patterns driven by climate change.

5.3. Extreme Weather Events and Contamination Spikes

Due to climate change, extreme weather events, such as floods, hurricanes, and storms, are becoming more frequent and severe [80]. These events can cause sudden and significant spikes in antibiotic contamination in freshwater ecosystems, potentially devastating consequences for water quality and ecosystem health. Floods and heavy storms can overwhelm wastewater treatment plants, releasing untreated or partially treated wastewater into nearby water bodies. This wastewater often contains high levels of antibiotics and other pharmaceuticals [37], quickly elevating contamination levels in the receiving waters. Additionally, extreme weather events can mobilize contaminants from sediments and soils [116], increasing their bioavailability and impact on aquatic ecosystems.

The sudden influx of antibiotics and other contaminants during extreme weather events can disrupt the balance of microbial communities, promote the spread of resistant bacteria, and increase the overall toxicity of the aquatic environment. These contamination spikes pose a severe threat to the resilience of freshwater ecosystems, particularly in regions already vulnerable to climate change’s effects.

5.4. Impact on Water Quality and Ecosystem Health

The cumulative effects of climate-induced changes in water temperature, flow, and chemistry can profoundly impact the overall health of freshwater ecosystems. Altered environmental conditions affect aquatic organisms’ growth, reproduction, and survival, making them more susceptible to the toxic effects of antibiotic contaminants. Changes in water temperature can stress cold-water species, reducing their ability to metabolize and detoxify antibiotics, leading to higher mortality rates. Increased temperatures can also alter the chemistry of cell membranes in aquatic organisms, making it easier for antibiotics to penetrate cells and potentially grow their toxicity [117]. This has been observed in the aquatic macrophyte Ricciocarpus natans when exposed to the antibiotic ciprofloxacin [55,118]. Similarly, altered flow regimes, such as changes in river flow patterns due to climate change, can disrupt the habitats of aquatic organisms [119]. These disruptions reduce species’ resilience to contamination, increasing the likelihood of population declines or shifts in species composition. Such changes can have cascading effects throughout the ecosystem, ultimately reducing biodiversity and destabilizing the environment. Furthermore, climate change can alter the composition of microbial communities in freshwater systems, influencing the development and spread of AMR [81,82]. Warmer temperatures and changes in water chemistry can favor the proliferation of resistant bacteria while also affecting interactions between different microbial species. These shifts can lead to new resistance patterns and the spread of ARGs across various environments, complicating efforts to manage antibiotic contamination and protect public health.

In conclusion, the impact of climate change on freshwater contamination by antibiotics is a multifaceted and complex issue. Rising temperatures, altered precipitation patterns, and extreme weather events contribute to freshwater ecosystems’ growing challenges. Addressing these challenges requires a comprehensive approach that integrates climate adaptation strategies with efforts to reduce antibiotic contamination and mitigate the spread of AMR.

6. Case Studies and Real-World Examples

6.1. Climate Change and AMR in Rivers

Examining specific case studies and real-world examples helps illuminate the complex interplay between antibiotic pollution and climate change in freshwater ecosystems. These cases provide insights into how these challenges manifest in different regions and what lessons can be learned to inform future management and policy decisions.

One of the most well-documented examples is the Yamuna River in India. The river, which flows through densely populated and industrialized areas, has become severely polluted due to the discharge of untreated sewage, industrial effluents, and agricultural runoff. The combination of antibiotic pollution and the region’s warm climate has created an environment where resistance can easily thrive and spread, affecting local communities and ecosystems downstream. Over the past 15 years, increased concentrations of various antibiotics, including ofloxacin, amoxicillin, and erythromycin, have been observed in the Yamuna River [120]. This increased concentration has been linked to the development of multiple antibiotic resistance in Escherichia coli [121]. Metagenomic analyses have also identified numerous ARGs and HGT elements in river sediment samples [122]. These findings were not observed in studies conducted a decade earlier [123].

Another significant case is the Mississippi River in the United States. The Mississippi River basin, which drains a large portion of the agricultural heartland of the United States, is heavily impacted by runoff from farms where antibiotics are widely used in livestock production. This runoff carries antibiotics and resistant bacteria into the river system. The region’s changing climate, characterized by more intense rainfall and flooding, exacerbates this issue by increasing the transport of these pollutants into the river [124]. Since 2011 [125], the frequency of ARGs in the Mississippi River has increased [124], turning the river into a conduit for the spread of antibiotic resistance. This affects aquatic ecosystems and the communities that rely on the river for water and food.

In China, a study on the Yellow River found that gradually increasing water temperatures (from 23 °C to 35 °C) led to a decrease in ARG diversity but a marked increase in their overall abundance [126]. Temperature was found to predict a significant portion of ARGs and mobile genetic elements (MGEs), with each 1 °C rise resulting in a substantial increase in ARG abundance, particularly for multidrug, tetracycline, and peptide resistance genes. Proteobacteria and Actinobacteria were identified as crucial ARG hosts. The study also highlighted that higher temperatures shifted ARG assembly from stochastic to more deterministic processes, leading to a rise in high-risk ARGs associated with opportunistic pathogens like Delftia spp., Legionella spp., and Pseudomonas spp., suggesting an elevated risk of antibiotic resistance under climate warming. Complementing these findings, research on river biofilms in a pristine German river revealed that increasing temperatures boosted the abundance of naturally occurring ARGs and affected the invasion dynamics of ARGs introduced via wastewater [127]. Biofilms exposed to higher temperatures (30 °C) experienced a rapid increase in naturally occurring ARGs after just one week. However, when these biofilms were exposed to a pulse of wastewater, the invasion of foreign ARGs was initially successful across all temperatures. Over time, though, the higher temperature (30 °C) accelerated the loss of these invading ARGs, returning ARG levels to natural baselines within two weeks. In contrast, at lower temperatures (20 °C and 25 °C), certain invading ARGs persisted and established themselves within the biofilm [127].

6.2. Lessons Learned from These Cases

The case studies of the Yamuna River in India, the Mississippi River in the United States, the Yellow River in China, and a pristine river in Germany provide critical insights into the intersection of antibiotic pollution and climate change in freshwater ecosystems. These examples highlight the complex and multifaceted nature of the challenges posed by these dual threats, revealing essential lessons that can inform future management strategies and policy decisions. One of the critical lessons learned from these cases is the need for an integrated approach to managing antibiotic pollution and climate change. The convergence of these two issues exacerbates their impacts, creating a compounded effect that is more difficult to manage. For instance, the Yamuna River illustrates how warm climates combined with high levels of antibiotic pollution create ideal conditions for the proliferation of antibiotic-resistant bacteria. This suggests that efforts to mitigate antibiotic pollution cannot be isolated from broader climate adaptation strategies. Effective management must simultaneously address the root causes of both issues, such as improving wastewater treatment infrastructure to reduce antibiotic discharges while implementing measures to adapt to and mitigate the effects of climate change.

Another important lesson is the critical role of monitoring and data collection. The studies on the Yellow River and the pristine German river demonstrate how temperature changes can influence the behavior of ARGs and their hosts. These findings underscore the importance of robust environmental monitoring systems that detect real-time changes. Regularly monitoring antibiotic levels, resistance patterns, and climatic conditions is essential for understanding the dynamic interactions between these factors and promptly responding to emerging threats. Moreover, the availability of comprehensive data is crucial for informing policymakers and guiding the development of effective regulatory frameworks. The case studies also highlight the importance of public awareness and education in combating antibiotic pollution and climate change. The persistence of antibiotic contamination in rivers like the Mississippi and Yamuna is partly due to the widespread use of antibiotics in agriculture and the improper disposal of pharmaceutical waste. Public education campaigns that raise awareness about the environmental impact of antibiotic use and promote responsible practices are essential components of any strategy to reduce antibiotic pollution. Furthermore, engaging local communities in monitoring and conservation efforts can foster a sense of stewardship and encourage sustainable practices.

Cross-border collaboration is another vital lesson from these cases, particularly for transboundary rivers like the Rhine or Mississippi. These rivers flow through multiple regions or countries, and managing their water quality and resistance levels requires coordinated efforts across borders. International cooperation is essential to harmonize policies, share data, and implement joint measures that can effectively address the spread of antibiotic resistance and mitigate the impacts of climate change on freshwater ecosystems. Finally, the findings from the Yellow River and German river studies demonstrate the need for adaptive management strategies. The variability in how different ARGs respond to temperature changes and other environmental factors suggests that management strategies must be flexible and adaptable. Policymakers and ecological managers must be prepared to adjust their approaches as new information becomes available and conditions evolve. This flexibility is crucial in a rapidly changing world where climate and environmental contaminants like antibiotics are subject to unpredictable shifts.

In conclusion, the lessons learned from these case studies emphasize the importance of a holistic, integrated approach to managing the intertwined challenges of antibiotic pollution and climate change. By combining robust monitoring, public education, cross-border collaboration, and adaptive management strategies, we can better protect freshwater ecosystems and reduce the spread of antimicrobial resistance. These efforts are essential for preserving biodiversity and ecosystem health and for safeguarding human health in an increasingly interconnected and warming world.

7. Mitigation Strategies

Advanced oxidation processes (AOPs), including ozonation and photocatalysis, are at the forefront of efforts to degrade persistent antimicrobials in wastewater. These technologies are highly effective in breaking down a wide range of pharmaceutical compounds, including antibiotics that are otherwise resistant to conventional wastewater treatment processes [128]. AOPs work by generating highly reactive species, such as hydroxyl radicals, which can non-selectively oxidize organic pollutants, leading to their complete mineralization or transformation into less harmful substances [128].

The primary advantage of AOPs is their ability to achieve high levels of contaminant removal, even for complex and persistent compounds. Ozonation, for instance, can effectively reduce the concentration of antibiotics in wastewater, thereby minimizing their release into the environment [128]. Photocatalysis, often using materials like titanium dioxide (TiO2), offers the added benefit of being activated by sunlight, making it a potentially energy-efficient solution [128]. However, these technologies also have disadvantages. AOPs typically require significant energy inputs, making them costly to operate on a large scale. Additionally, the byproducts generated during oxidation can sometimes be more toxic or persistent than the parent compounds, necessitating further treatment. The infrastructure required for AOPs is also complex and may not be feasible for all wastewater treatment facilities, particularly in regions with limited resources [129].

In contrast, natural-based solutions, like constructed wetlands and bioreactors, offer a more sustainable approach to removing pharmaceuticals, including antibiotics, from wastewater. Constructed wetlands mimic natural wetland ecosystems, using plants, soil, and associated microbial communities to filter and degrade contaminants [130]. Conversely, bioreactors are engineered systems that leverage specific microbial communities to break down pharmaceuticals in a controlled environment [131]. The advantages of natural-based solutions are numerous. They are generally more cost-effective than advanced technologies, as they rely on natural processes that require less energy and fewer chemical inputs [130]. Constructed wetlands, for example, can provide a long-term, low-maintenance solution for wastewater treatment while offering additional ecological benefits, such as habitat creation and carbon sequestration [130]. Bioreactors can be designed to target specific contaminants, making them highly versatile and adaptable to different wastewater compositions [131]. However, these solutions also have limitations. Environmental conditions, such as temperature, pH, and competing pollutants, can influence the effectiveness of constructed wetlands and bioreactors. Seasonal variations can also impact these systems’ performance, leading to treatment efficiency fluctuations. Additionally, natural-based solutions typically require larger land areas than conventional technologies, which can be a constraint in densely populated or industrialized regions [130].

Beyond wastewater treatment, improved agricultural practices are critical in reducing the reliance on antimicrobials and preventing their entry into freshwater systems. Precision farming techniques, for instance, allow for the targeted application of antibiotics and other agrochemicals, minimizing their use and reducing the risk of environmental contamination. Integrated pest management (IPM) emphasizes using biological controls and other non-chemical methods to manage pests and diseases, reducing the need for antibiotics in agriculture [132]. The advantage of these practices lies in their ability to maintain or even enhance agricultural productivity while minimizing environmental impact. By reducing the volume of antimicrobials used in farming, these practices also help slow the development of resistance in both agricultural and natural environments. However, adopting precision farming and IPM requires significant investment in technology and training, which may be a barrier for some farmers, particularly in developing regions [132].

Effective policy frameworks and regulations are essential for managing antimicrobial contamination and AMR. Rules governing the use and disposal of antimicrobials in agriculture, industry, and households are necessary to minimize environmental contamination. International cooperation and the harmonization of standards are essential due to the transboundary nature of water systems and the global spread of AMR. Policies that mandate the proper disposal of pharmaceutical waste, restrict the non-essential use of antibiotics, and promote the development of alternative treatments are critical components of a comprehensive AMR management strategy. Additionally, regulations that require the implementation of advanced wastewater treatment technologies or the use of natural-based solutions in appropriate contexts can significantly reduce the release of antimicrobials into the environment. The primary challenge in implementing these policies is ensuring compliance across different sectors and regions. Effective enforcement mechanisms and incentives for compliance are necessary to achieve widespread adherence to these regulations. Moreover, the complexity of AMR as a global issue requires coordinated efforts across national borders, which can be challenging to achieve in practice.

Public awareness and education campaigns promote responsible behavior and drive policy action [133]. These campaigns can highlight the risks associated with antimicrobial contamination and AMR, encouraging antimicrobials’ responsible use and disposal. They can also emphasize the importance of environmental stewardship and the need for robust regulatory frameworks to protect public health and preserve freshwater ecosystems. Effective public engagement can lead to greater community involvement in monitoring and managing water quality and increased support for policies aimed at reducing antimicrobial contamination. However, the success of these campaigns depends on clear communication and the ability to reach diverse audiences, including those in regions most affected by antimicrobial pollution.

In conclusion, mitigating the impact of antimicrobial contamination and AMR requires a multifaceted approach that integrates advanced technologies, natural-based solutions, improved agricultural practices, robust policy frameworks, and public education. Each strategy has its advantages and challenges, and the most effective solutions will likely involve a combination of these approaches tailored to the specific needs and conditions of the affected regions. By leveraging the strengths of both conventional and innovative strategies, we can better protect our freshwater resources and safeguard the health of both ecosystems and human populations.

8. Future Directions and Research Gaps

Future research should prioritize identifying and characterizing emerging antimicrobial contaminants that threaten freshwater systems. This includes newly developed pharmaceuticals and biocides and their metabolites and transformation products, which may exhibit different environmental behaviors and impacts compared to their parent compounds. Understanding these emerging contaminants is crucial for anticipating and mitigating potential threats to aquatic ecosystems. Equally important is the need to study the long-term impacts of climate change on antimicrobial contamination and the spread of AMR. As climate change alters temperature, precipitation patterns, and water flow, it will likely influence the fate, transport, and effects of antimicrobial contaminants and the evolution and dissemination of resistance genes. Research in this area is critical for developing adaptive management strategies that can respond to the dynamic challenges posed by a changing climate.

Integrating approaches that combine technological, regulatory, and behavioral interventions is essential to effectively managing and mitigating the risks associated with antimicrobial contamination and AMR. This includes developing holistic water management frameworks that account for the complexities of antibiotic pollution and climate change. Interdisciplinary research collaborations will be necessary to address these multifaceted challenges, bringing together expertise from environmental science, microbiology, public health, and policy. Additionally, engaging diverse stakeholders in decision-making will ensure that management strategies are practical, equitable, and widely supported.

In summary, addressing the future challenges of antimicrobial contamination and AMR in freshwater systems requires a proactive and collaborative research agenda. By advancing our understanding of emerging contaminants and the effects of climate change and by integrating technological, regulatory, and behavioral solutions, we can better protect aquatic ecosystems and public health in the face of these growing threats.

9. Conclusions

In conclusion, the convergence of antibiotic contamination, resistance, and climate dynamics in freshwater ecosystems presents a complex and increasingly urgent challenge. As global temperatures rise and weather patterns become more erratic, the interaction between these factors intensifies, leading to profound and far-reaching impacts on aquatic environments. This convergence is evident in how climate change exacerbates the persistence and spread of antibiotics in water bodies, accelerating the development and dissemination of AMR. The Yamuna River, Mississippi River, Yellow River, and pristine German river case studies illustrate how this intersection manifests across different regions, each grappling with the compounded effects of antibiotic pollution and climate change. These examples highlight the critical need for an integrated approach to addressing these intertwined issues. Advanced technologies, like oxidation processes, alongside natural-based solutions, such as constructed wetlands and bioreactors, offer promising methods for mitigating antibiotic contamination. However, the success of these interventions depends on robust policy frameworks, international cooperation, and public engagement to manage the transboundary nature of water systems and the global spread of AMR. The future demands a comprehensive strategy that leverages scientific innovation and integrates regulatory, technological, and behavioral interventions to safeguard freshwater ecosystems. As climate dynamics evolve, so must our approaches to managing antibiotic contamination and resistance. By addressing this convergence with urgency and coordinated action, we can better protect both environmental and public health, ensuring the resilience of our freshwater resources in an increasingly challenging global landscape.