Antimicrobial resistance (AMR) occurs when bacteria and other organisms acquire resistance mechanisms, [1] rendering antibiotics ineffective and making infections more difficult to treat [1] . AMR is a growing concern in clinical applications, with several pathogens developing resistance to multiple classes of antimicrobials. While previous reviews have focused on the mechanism of antibiotic resistance and its spread, especially in healthcare settings [2] - [5] , less research has been conducted on the maintenance of antibiotic resistance in the environmental settings.

Compared to gram-positive bacteria, gram-negative bacteria demonstrate greater resistance to antibiotics and chemotherapeutic agents [6] . This can be attributed to their outer membrane, which limits the penetration of hydrophilic solutes, as well as the low fluidity of the lipopolysaccharide leaflet [6] . Additionally, these bacteria possess multiple drug efflux pumps that further contribute to their resistance capability [6] .

A paper by Nikaido et al. (1998) [6] explains the function of these efflux pumps. Spanning both the inner and outer membranes of gram-negative bacteria, these pumps are powered by the proton-motive force, allowing them to expel a wide range of substances, including detergents, dyes, and antibiotics. They can also eliminate compounds such as beta-lactams, which typically have difficulty crossing the cytoplasmic membrane. Overexpression of these efflux pumps can significantly increase the minimum inhibitory concentrations (MICs) of antibiotics, contributing to the high resistance observed in gram-negative bacteria.

This literature review aims to explore and attempts to answer how we can prevent pathogenic bacteria from passing multidrug resistant (MDR) genes to non-pathogenic bacteria in the environment by analyzing current information on gram-negative AMR in water sources.

The environment can become contaminated with antibiotics due to human and animal waste, pesticide use, pharmaceutical manufacturing wastage, and aquaculture [7] . This is a major problem since these factors contribute to the spread of resistance among human populations [7] .

Firstly, human waste contains traces of antibiotics [7] . Unfortunately, wastewater treatment plants (WWTPs) are unable to remove all antibiotic residues and resistant genes [7] . This is especially seen in wastewater from hospitals where patients are prescribed antibiotics and antifungals [7] . A study by Berglund et al. (2023) investigated the emergence of mobile antibiotic resistance genes (ARGs) in wastewater environments [8] . They analyzed 22 bacterial species and determined the taxonomic origins of mobile ARGs based on previous research. The results showed that these species originated from wastewaters and human stool. The researchers focused on Mobilizing Insertion Sequence Elements (MISE) and their presence in the genome of the origin species. They examined complete genomes and metagenomic data to determine the environments where MISE are abundant. The findings revealed that MISE are present in untreated hospital effluent, wastewater treatment plant influent, and poultry feces [8] . Additionally, the study demonstrated that origin species carrying ARGs are more commonly observed in wastewaters and contaminated water/sediments, which may be linked to human feces [8] . The authors suggest that the mobilization of ARGs in human and animal microbiota occurs as a response to the selective pressure of antibiotics, given the connection between these species and infections [8] .

Secondly, antibiotics used in livestock production, ultimately lead to contamination of soil and water sources [7] . The use of untreated animal manure as fertilizer can also contribute to the spread of resistant bacteria in the environment [7] . In the US, over 25 million pounds of antimicrobials are used annually in food-animal production, with approximately 13.5 million pounds of antibiotics being excreted in animal fecal waste each year [9] . These waste products containing antibiotics can enter the environment through various pathways such as manure, soil, runoff, or by being discharged as wastewater effluent into surface water and sediment [9] . In a paper by Williams et al. (2016) where the characterization of AMR among aquatic environments is reviewed [10] , they determined that surface water from which drinking water originates, is the discharge point for wastewater as well as runoff from animal farms [10] . This causes the spread of AMR between humans and animals [10] . In this article, studies discussing AMR in surface and recreational waters, municipal wastewater, healthcare-associated wastewater, airplane wastewater, industrial wastewater, farm animal wastewater, and aquaculture were reviewed. It also explored treatment technologies such as disinfection, activated sludge digestion, sludge composting, swine vermicomposting, fertilization, ionic liquid, and drinking water treatment as potential ways to prevent dissemination of AMR into the environment.

Additionally, the use of pesticides in agriculture to mitigate crop diseases leads to the contamination of soil and water, also leading to resistance in the environment [7] . Human health can be affected when these pesticides are similar to antibiotics used in human medicine [7] . A paper titled “The source, fate and prospect of antibiotic resistance genes in soil: A review” highlights the impact of ARGs on public health in soil environments specifically. Soil is a reservoir and propagation hotspot for ARGs [11] . Factors like microbiome composition, soil physicochemical properties (pH and moisture), antibiotics, heavy metals, polycyclic aromatic hydrocarbons, and pesticides, were discussed in relation to their impact on ARGs. Among these factors, microbial community structure, mobile genetic elements, pH, and heavy metals were identified as having a significant influence on ARG profiles [11] .

Aquaculture operations frequently use antibiotics, leading to contamination of water sources [7] . A study by Doğan and Önalan (2023) [12] aimed to determine the variations of antimicrobial resistance genes (specifically tet and str genes that confer resistance to tetracycline and streptomycin respectively) in freshwater fish species. Antimicrobial resistance is a concerning issue in public health, and understanding the presence and diversity of resistance genes in different environments, such as freshwater ecosystems, can provide insights into potential sources and pathways of resistance transmission [12] . By analyzing these genes in freshwater fish species, the researchers sought to contribute to our understanding of antimicrobial resistance dynamics in aquatic environments [12] . The researchers sampled 70 fish belonging to seven different species. They were collected from two regions, one region with no fish farming activities and another region with fish farming activities. They found that two species, C. carpio and C. regium had higher tet and str gene expression compared to a control group which had no antibiotic use [12] . In other species, a lower but significant expression level was seen [12] . The researchers concluded that even in the absence of antibiotic use, the fish recirculating water system can cause the spread of antibiotic resistance genes [12] . Other factors such as pH and heavy metals can also contribute [12] . Ultimately, the ecosystem serves as a connection between humans, animals, and the environment [13] . AMR transmission and the mixing of mobile genetic elements are thus able to spread to hosts [13] . A paper by Samreen et al. (2021) [13] describes how biocides and heavy metals contribute to the development and dissemination of AMR. These metals have resistance mechanisms similar to antibiotics such as reduced membrane permeability, metal alteration, efflux of metals, target site modification, and metal sequestration. Biocidal products exert microbiostatic or microbicidal effects against various microorganisms.

Antibiotic resistance in bacterial species occurs through various mechanisms, including genetic mutations, horizontal gene transfer, and selective pressure from the overuse and misuse of antibiotics. When bacteria are exposed to antibiotics, those with mutations that confer resistance to the drug are more likely to survive and propagate, passing on these resistant traits to their progeny. Horizontal gene transfer allows bacteria to acquire resistance genes from other bacteria, further spreading resistance across species. The global issue of antibiotic resistance is exacerbated by the extensive and often inappropriate use of antibiotics in both human healthcare and agriculture, creating an environment in which resistance can thrive [14] . Additionally, the overprescription of antibiotics for viral infections, lack of proper diagnostics, and inadequate infection control measures contribute to the accelerating spread of resistance [15] . As bacteria evolve to resist multiple classes of antibiotics, previously treatable infections become increasingly difficult to manage, leading to higher mortality rates, prolonged hospital stays, and greater healthcare costs. The World Health Organization (WHO) has classified antibiotic resistance as one of the most urgent global health threats, as it undermines the effectiveness of life-saving antibiotics and limits treatment options for common infections, such as pneumonia, tuberculosis, and urinary tract infections [16] . The interconnected nature of global travel, trade, and food supply chains further facilitates the spread of resistant bacteria across borders, making this a problem that requires urgent global cooperation and action.

The World Health Organization (WHO) has highlighted several critical pathogens that pose an immediate threat due to their increasing resistance to available treatments. Among these, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa are notable examples. Recent studies have shown that E. coli is particularly concerning due to its growing resistance to fluoroquinolones and third-generation cephalosporins, often driven by the acquisition of extended-spectrum beta-lactamases (ESBLs) and carbapenemases [17] . Similarly, K. pneumoniae has seen an alarming rise in carbapenem resistance, linked to the spread of New Delhi metallo-beta-lactamase (NDM)-producing strains [18] . S. aureus, including methicillin-resistant strains (MRSA), remains a significant hospital-acquired pathogen, with a troubling trend toward multidrug resistance [19] . P. aeruginosa, notorious for its environmental resilience, has shown increasing resistance to beta-lactams, aminoglycosides, and fluoroquinolones, complicating treatment options [20] . These species, among others, exemplify the broader issue of ABR, which threatens to undermine the effectiveness of antibiotics, complicating the treatment of infections and increasing morbidity and mortality worldwide. Recent literature continues to underscore the urgency of global surveillance and the need for innovative solutions to combat this growing resistance crisis.

This review will narrow its focus to a specific bacterial genus, Salmonella, which continues to be of concern in both environmental and clinical contexts. There are physiological, biochemical, environmental, and molecular factors that allow for its resistance [21] . S. enterica is a gram-negative bacterium that is passed through contaminated food and water between humans and animals [22] . Salmonellosis causes gastroenteritis, septicemia, and enteric fever. Enteric fevers are caused by S. enterica serovars Typhi and Paratyphi [22] , which are human-restricted. The epidemiology of typhoid and other enteric fevers involve person-to-person transmission because these organisms do not have a significant animal reservoir [23] . Unlike Typhi and Paratyphi, nontyphoidal Salmonellae (NTS) are not human-restricted [22] . The S. enterica serotypes Typhimurium and Enteritidis have reservoirs in farm animals, thus consumption of contaminated and raw meat is the main mode of NTS transmission [23] . Nontyphoidal salmonellosis is similar to gastroenteritis as symptoms may involve nausea and diarrhea [22] . Salmonella can also cause chronic conditions such as Reiter’s syndrome, a form of arthritis [22] . Salmonellae have a lipopolysaccharide coat and possess the ability to invade cells and replicate intracellularly [23] . These bacteria are found in the ileum and colon and they invade the intestinal epithelium by binding to receptors on the epithelial cell surface, leading to an acute inflammatory response [23] . In a recent study by Robertson et al. (2023) [24] , Illumina sequencing data was used to provide a current characterization of plasmids and their AMR associations within the Salmonella species. About 16% of Salmonella cases in the US exhibit resistance to at least one essential antibiotic [24] . Bacteria can acquire antibiotic resistance through mutations or mobile genetic elements (MGEs) that carry genes that confer this resistance [24] . Plasmids are an example of MGEs which allow for horizontal transfer of AMR genes [24] . Although mostly circular, linear plasmids are found in some gram negative bacteria like Salmonella [24] . Linear plasmids are found to confer advantages such as enhanced nuclear translocation [25] . The authors describe replicon and relaxase typing as efficient methods for plasmid classification which give us information on AMR and virulence [24] . The results of this study were that Salmonella virulence plasmids were largely inherited vertically and that plasmids identified in this bacterium have the ability to replicate in other pathogens and be transferred between commensal and pathogenic bacteria [24] . Vertical transfer is when the plasmid is transported from the mother to daughter cells during cell division, whereas horizontal transfer occurs through conjugation [26] . In vertical transfer, cells divide and produce copies of themselves, leading to more cells over time [26] . This mode of transfer also ensures that resistance traits are inherited by subsequent generations [26] .

Another group of pathogenic bacteria, the “ESKAPE” pathogens include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). These pathogens can escape bactericidal activity of antibiotics, making them a great threat to human health [27] . Figure 1 highlights their mechanisms of antibiotic resistance. In a review paper by Marutescu et al. (2023), it was found that WWTPs provided these bacteria with additional virulence determinants [28] . Of these pathogens, those that are mostly found in the environment are P. aeruginosa and enterococci.

P. aeruginosa, an aerobic gram-negative bacterium is found in the environment and causes nosocomial infections [27] . It demonstrates both intrinsic and acquired mechanisms of resistance including efflux pumps, decreased outer membrane permeability, and lack of proteins that allow diffusion of antibiotics across the outer membrane [27] . Due to this bacterium being adapted to low osmolarity environments, it is often found in water sources. 95% of hospital wastewater samples were positive for multidrug-resistant P. aeruginosa in this study. In a paper by Gervasoni et al. (2023), this bacterium’s ability to form biofilms was discussed. Due to this, they are found in a variety of aquatic environments [29] .

Enterococci are gram-positive cocci which can survive in hostile environments. E. faecalis and E. faecium cause most of the enterococcal infections [27] . This bacterial species is becoming increasingly resistant due to various reasons including the large use of broad-spectrum antibiotics in hospitals [27] . Broad spectrum antibiotics include penicillins and cephalosporins which increase normal gram-negative intestinal microbiota, thereby promoting intestinal colonization of E. faecium [27] . A genomic analysis by Shobo et al. (2023) provided information on the spread of E. faecalis in hospitals as well as its acquisition of resistant genes is such settings [30] . The researchers found that this specie was responsible for over 80% of hospital cases and can acquire additional resistance through the transfer of plasmids, prophages, insertion sequences, and other mobile genetic elements [30] . Another study by Paul B. Tchounwou (2015) isolated Enterococcus species in hospital wastewater and effluent of WWTPs instead of looking at the internal hospital environment [31] . He determined that 62 of the 66 isolates belonged to the Enterococcus genus, with majority being E. faecalis [31] . In these isolated species, he found a high number of genotypic virulence factors including Zn-metalloendopeptidase (gelE), collagen binding protein (ace) and endocarditic antigen (efaA) [31] .

Pathogenic bacteria cause disease and invade host cells whereas non-pathogenic bacteria do not. Non-pathogenic bacteria may however carry genes which increase a pathogen’s ability to amplify and spread [42] . A paper by Dionisio et al. (2023) [42] discusses non-pathogenic bacteria and their involvement in the dissemination of virulence and resistance genes. The authors discuss their ability to possess virulent genes, drug resistance genes, as well as non-housekeeping genes that can enhance the success of pathogens during infection [42] . Non-pathogenic cells that lack these genes can aid in the transfer of such genes to pathogenic cells by amplifying their presence within microbiomes [42] . Additionally, physical contact networks involving humans contribute to the transmission of pathogens within our population [42] . These networks refer to physical contact between families, friends, and sexual relationships.

A paper by José L. Martínez (2012) [43] discusses bottlenecks modulating the transfer, spread, and stability of antibiotic resistance genes. Since human pathogens acquire resistance genes via horizontal gene transfer originating in non-pathogenic bacteria, it is important to consider how natural, non-clinical ecosystems contribute to the evolution of resistance [43] . The author analyzed factors such as founder effects, ecological connectivity, fitness costs, and second-order selection [43] . The founder effect refers to a situation where the first transferred gene becomes dominant [43] . When multiple resistance genes with similar profiles are present, one gene typically prevails in human bacterial pathogens [43] . This outcome can be influenced by fitness costs and chance. For example, the TEM-1 beta-lactamase became predominant among Enterobacteriaceae family members after its acquisition and rapid spread [43] . Although many beta-lactamases exist, TEM-1 prevailed due to strong selective pressure from antibiotics [43] . However, the introduction of new antibiotics or inhibitors can lead to the evolution of different beta-lactamases [43] . Ecological connectivity is related to both the spatial arrangement of microorganisms and their ability to transfer genetic material [43] . In natural environments, there is a low concentration of antibiotics unlike human-related environments like WWTPs [43] . In environments like WWTPs, human pathogens and non-pathogenic bacteria coexist, so there is a higher chance for the transfer of resistance genes to bacterial pathogens [43] . Also, some microorganisms form genetic exchange communities which share features like plasmids or transposons [43] . Therefore, if a mobile genetic element carrying a resistance gene enters a genetic exchange community, it can cause the gene to become fixed in bacterial pathogen populations [43] . The spread in certain bacteria is however limited by fitness costs because some resistant bacteria are outcompeted by susceptible ones [43] . Fitness costs may be compensated by mutations that allow resistance to persist [43] . Lastly, resistance genes can be maintained in habitats without strong antibiotic pressure through second-order selection [43] . This refers to when selection for one antibiotic can select for the entire array of resistance genes on a specific genetic element [43] . Cross-selection is another process where selection for one compound results in resistance to another, such as multidrug efflux pumps conferring resistance to antibiotics, biocides, and heavy metals [43] . Plasmids may also encode stability systems that increase the chances of resistance gene maintenance [43] .

Plasmids allow for the possibility of rapid horizontal transfer of resistance among bacterial populations [44] . This is highlighted in a paper titled “Dissemination of plasmid-encoded AmpC β-lactamases in antimicrobial resistant Salmonella serotypes originating from humans, pigs and the swine environment”. MDR Salmonella carries resistance genes on either their chromosome or mobile genetic elements [44] . Commercial agriculture offers a reservoir for MDR genes that could potentially be exchanged through horizontal transfer [44] . In this study Salmonella strains were selected from humans, pigs and the farm environment to determine if the exchange of material is possible [44] . MDR plasmids were found in all isolates. Those taken from pigs and their environment had the highest frequency of MDR [44] . All three sites contained similar resistance profiles. Class I and II integrons were also found and could be important to the transfer of MDR genes [44] . Similar plasmid profiles were also associated with serotypes that contained the same MDR pattern on all samples from different sites [44] .

Multiple drug resistance (MDR) in Enterobacteriaceae, particularly Salmonella and Escherichia coli, is a major public health concern due to plasmid-mediated gene transfer. We analyzed Salmonella enterica clinical isolates for plasmid-borne MDR transfer to E. coli and assessed the fitness impact of carrying an Inc A/C plasmid. Our findings show that Inc A/C plasmids provide a fitness advantage in macrophages without imposing significant costs under stress conditions. These results highlight the role of plasmids in enhancing pathogenicity and underscore the need to better understand MDR dissemination mechanisms [45] .

In another review paper titled “Plasmids, a Molecular Cornerstone of Antimicrobial Resistance in the One Health Era”, plasmid-mediated AMR and its mechanisms is discussed in detail. Plasmids not only spread ARGs between bacteria within the same microbiome, but also between microbiomes, and habitats, as well as between animals, humans, and the environment as shown in Figure 2 [46] .

ARGs are spread among bacteria by conjugation between bacteria which is the transfer of DNA and is facilitated by plasmids or by integrative conjugative elements (ICEs) [46] . Some conjugative plasmids can even mobilize genes from plasmid recipients back to plasmid donors, a process called retromobilization, expanding their ecological role [46] . Plasmids vary in size, and are categorized as conjugative, mobilizable, or non-mobilizable based on their ability to encode or use conjugative machinery [46] . They contain genes essential for conjugation, alongside other genes responsible for stable maintenance, regulatory control, and replication of the plasmid [46] . Additionally, plasmids often possess “accessory” regions, housing genes that promote their own or their host’s survival, such as toxin-antitoxin genes, metal and antibiotic resistance genes, virulence genes, as well as metabolic and catabolic functions [46] . These accessory regions can vary between plasmids due to recombination events, resulting in mosaic plasmids. Mosaic plasmids contain genetic elements from different sources and are more prevalent among clinically relevant genera like Escherichia, Klebsiella, or Salmonella [46] . They also carry a higher proportion of transposase and antibiotic resistance genes [46] . In another paper by Li and Zhang (2023) [47] , stressors that influence the transfer of plasmid mediated ARGs in the environment are discussed. These include environmental pollutants, including metals, pharmaceuticals, disinfectants, and microplastics [47] .

There are several recent studies which highlight treatments and processes to combat AMR.

A paper by Azuma et al. (2022) [58] , discusses the inactivation of antibiotic-resistant bacteria in wastewater by ozone-based advanced water treatment processes [58] . Many recent studies examined methods such as Fenton treatment, ultrasonication, electrolysis, TiO₂ photocatalysis, persulfate oxidation, graphitic carbon nitride (g-C₃N₄) treatment, UV/chlorine treatment, and ozone (O₃) treatment for water disinfection [58] . However, among these techniques, ozone (O₃) is notable for its strong oxidation capability and effectiveness in decolorization, deodorization, and sterilization [58] . Ozone treatment has demonstrated efficacy not only in inactivating pathogenic microorganisms but also in removing micropollutants such as pharmaceutical residues and endocrine disruptors from wastewater [58] . This study’s results were that this treatment inactivates antimicrobial resistant and sensitive bacteria after ten minutes of treatment [58] .

Another paper explored the potential of bacteriophages as a strategy for controlling antibiotic-resistant pathogens and understanding microbial interactions in wastewater treatment systems. Bacteriophages are viruses that infect and kill bacteria and are a potential alternative to antibiotics [59] . This paper cites their advantages which include their ability to target specific bacteria, their low toxicity, their effectiveness against ARBs and biofilms, and their ability to reproduce in response to pathogen density [59] . They also discuss various studies in which bacteriophages were able to successfully treat antibiotic-resistant bacteria in wastewater. For example, they have been effective against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, reducing bacterial populations and antibiotic resistance [59] . Another application of bacteriophages that is discussed in this paper is against membrane fouling, or formation of biofilms on membrane bioreactor systems which are used in the treatment of wastewater [59] . Several studies discussed in this paper demonstrate the ability of bacteriophages to target bacteria in biofouling. The authors of this paper concluded that lytic phages are preferred to avoid horizontal gene transfer [59] .

Additionally, a study by Iakovides et al. (2019) [60] discussed continuous ozonation of wastewater as a promising treatment for the elimination of the selected antibiotics, ARBs, and ARGs [60] . The schematic of this treatment process is seen in Figure 3 .

A paper by Le et al. (2018) [61] , discusses the removal of antibiotic residues, ARBs, and ARGs by membrane bioreactor systems. This research paper presents extensive data on the presence of 19 antibiotics, 10 types of antibiotic-resistant bacteria, and 15 antibiotic resistance genes (ARGs) in the untreated wastewater influent as well as during various treatment stages of conventional activated sludge (CAS) and membrane bioreactor (MBR) systems. The findings indicate that MBR systems demonstrated superior performance compared to CAS systems in terms of removing antibiotic-resistant bacteria, antibiotic resistance genes, and the majority of the target antibiotics [61] .

Also, the paper titled “Increasing antimicrobial susceptibility of MDR Salmonella with the efflux pump inhibitor 1-(1-Naphthylmethyl)-piperazine” discusses the importance of developing effective measures against Salmonella due to its multidrug resistance. Bacterial antibiotic resistance is frequently mediated by efflux pumps [62] . In this research, the efficacy of two compounds, 1-(1-Naphthylmethyl)-Piperazine (NMP) and Phenylalanine-arginine β-naphthylamide (PaβN), in inhibiting efflux pump activity was investigated [62] . Specifically, their potential to synergistically enhance the effectiveness of the antibiotic tetracycline against tetracycline-resistant Salmonella was examined [62] . The findings revealed that these Efflux Pump Inhibitors (EPIs) were able to significantly reduce Salmonella’s resistance to tetracycline, with a 16 to 32-fold decrease observed in multiple tetracycline-resistant isolates [62] .

Lastly, a review by Alaa Qumsani (2023) examines the potential of nanoparticles (NPs) as a highly efficient method to combat bacteria. NPs act both as carriers for natural antibiotics and antimicrobials as well as active agents against bacteria [38] . Moreover, the surface engineering of nanocarriers allows for targeted delivery and modification of various resistance mechanisms [38] . However, a limitation of this drug-delivery method is clearance through the reticuloendothelial system [38] . Overall, however, the use of NPs is a promising technique for overcoming bacterial resistance.

While antimicrobial resistance (AMR) is monitored in clinical settings, there is a lack thereof in environmental settings and AMR in environmental settings poses a significant threat to public health. Understanding the environmental aspect of AMR is crucial to understanding the routes of dissemination, selection of resistant microorganism, and risks posed to human health [63] .

This review highlights the issue of antimicrobial resistance in the environment, with an emphasis on water sources. A significant area of concern is wastewater treatment plants, especially in hospital plants, which serve as hotspots for the selection of ARGs and their diffusion in the environment [41] . Of particular concern is the role of horizontal gene transfer in facilitating resistance gene dissemination among pathogenic and non-pathogenic bacteria. This literature review also discussed multidrug resistant Salmonella strains. NTS is spread through many ways including the fecal-oral route, contaminated food, animal contact, and rarely person-to-person [64] . Future steps involve reviewing recent studies which highlight treatments and processes to combat AMR. Ideas discussed in this literature review are ozone-based advanced water treatment processes, bacteriophages, ozonation, membrane bioreactor systems, and efflux pump inhibitors. These strategies show promise in combating AMR, however, improvement in local government policies in regulating antibiotic pollution and enhancements to wastewater treatment capabilities, are necessary in solidifying the battle against AMR.

Publishing this review is essential to raise awareness of the increasing difficulty in treating antibiotic-resistant infections. Without intervention, the continued spread of AMR could render current treatments ineffective, leading to severe public health consequences.