A Crossroads of Global Health and Sustainability in the point of Antimicrobial Resistance

 

Yin Myo Thant1*, Mohammad Chand Jamali2, Rabindra Dev Prasad3, Srikumar Chakravarthi4, Yuldashev Bakhrom5, Nikolaus Syrmos6, Ms. Shokhida Rasulova Shukhrat Kizi7

1Department of Education and Liberal Arts, INTI International University, Malaysia.

2Faculty of Medical and Health Sciences, Liwa College, Al Ain, Abu Dhabi, United Arab Emirates

3Dean, Faculty of Education and Liberal Arts INTI International University, Malaysia.

4Deputy Vice Chancellor (Academic, Research, Innovation), SEGi University,  Selangor, Malaysia.

5DSC, Professor, Dean of the Faculty of Medicine, Mamun University, Khiva, Uzbekistan.

6Human Performance and Health, Aristotle University of Thessaloniki, Thesaaloniki, Macedonia, Greece.

7Department of Education and Liberal Arts, INTI International University, Malaysia.

*Corresponding Author E-mail: tthant273@gmail.com, mjamali68@gmail.com, rabindra.prasad@newinti.edu.my, srikumarc@segi.edu.my, baxrom@mamunedu.uz, milanako76@yahoo.gr, shohida98@gmail.com

 

ABSTRACT:

Antimicrobial resistance (AMR) is becoming an international threat leading to the failure of modern medicine as well as the progress toward the United Nations Sustainable Development Goals (SDGs), specifically SDG 3 (Good Health and Well-being), SDG 6 (Clean Water and Sanitation), and SDG 12 (Responsible Consumption and Production). AMR is developed when microorganisms become resistant to antimicrobial drugs through evolutions and becomes ineffective to the treatments thus causing high mortality, prolonged hospital stays, and escalated health expenditures. What makes this crisis grow are factors including the abuse of antibiotics usage both in the health of humans and animals, the poor regulation of such use, poor sanitation, and even a general unawareness in developing and middle-income countries. Resurgent surveillance data indicate high levels of resistance to common pathogens such as Escherichia coli, Klebsiella pneumonia and MRSA among others across the regions. An AMR solution would demand a One Health approach, which addresses the solutions to human, animal, and environmental health. The most important of them are antimicrobial stewardship programs (ASP), better diagnostics, infection control, and investment in new therapeutics. To curb the spread of AMR, efficient policy frameworks, international cooperation and community participation are essential. Unless action is taken immediately and in organized effort, AMR will represent 10 million deaths per year by 2050, with most falls being on vulnerable populations. The fight against AMR is a must to have fair, stable, and sustainable systems of healthcare in line with the global development goals.

 

KEYWORDS: Antimicrobial resistance (AMR), SDG 6, SDG 12, Healthcare, Global Development.

 

 


 

 

INTRODUCTION:

Antimicrobial resistance (AMR) is identified as the formation of the microorganisms’ defenses against the impacts of antibiotics and other antimicrobial agents, i.e., viruses, fungi, parasites, and bacteria.  The growing resistance of diseases towards antibiotics and the delay in producing new medication to treat these diseases have led to this situation becoming one of the most important in the recent history of the world1. One of the factors that have contributed to the epidemic is the excessive and misuse of antibiotics which are used in a variety of estate, such as agriculture, healthcare, veterinary medicine and food production. Dubbed by some as a silent pandemic, antimicrobial resistance (AMR) has become a high priority issue that needs to be acted upon now2. Antibiotics meant the revolution of medicine and lives of millions of people were saved. Breakthroughs like the discovery of penicillin by Alexander Fleming in 1928 and the present World War II age of antibiotic research that was characterized by the introduction of streptomycin, chloramphenicol, tetracyclines, vancomycin and cephalosporins revolutionized the mode of treatment of infectious diseases3. Nevertheless, during the last several decades, the efficacy of these life-saving medications has been reduced with the appearance of antibiotic-resistant bacteria, and an international re-evaluation of the use of antibiotics and the introduction of stewardship initiatives have been suggested. Antibiotic resistance has become one of the contributing factors of morbidity and fatality throughout the world4. The presence of multidrug-resistant pathogens has made most of the conventional methods of treatment ineffective, and more than 670,000 anti-microbial resistance related infections are reported yearly in the European Union. The AMR cost the work in 1.27 million deaths in 2019 directly due to drug-resistant bacterial infections and 4.95 million deaths in total. The problem is that within the next thirty years the number of deaths may surpass 10 million deaths annually due to AMR and Asia and Africa experiences the greatest numbers because of the population and the lack of regulatory processes. The results of the 2019 Global Burden of Disease study indicated that Sub-Saharan Africa had the greatest number of deaths related to AMR, and in comparison, Australia had the lowest5. Antimicrobial resistance (AMR) is a complex multisided problem to the human health, animal health, and environment. Its consequences go outside the field of clinic; they affect agricultural process and the food chain destroying environmental stability. Passive use of antibiotics was put at higher rate with the activities of man that have promoted rapid evolution and spread of antibiotics resistant Bacteria. In the last few decades, the rates of antibiotic resistance continually rose and now it is a severe threat to our health worldwide6. Thus, quite numerous antibiotics lost their effectiveness or became ineffective against infections as the mechanisms of resistances are shared among a set of different bacterial species. This has contributed to enhancement in severity of simple infections, increased hospitalization stays, increased expense of medical care and high mortality level7. Inappropriate use of antibiotics, exorbitant cost of treatment, environmental contamination, healthcare-associated transmission (Table 1), and the long process of developing new antibiotics are other factors that contributed to AMR, illustrating the necessity to implement multipronged tools to resolve this crisis8.


 

Table 1: Factors identified as driving global antimicrobial resistance8

Factors

Plain language translation

Mass drug administration in human health

Mass drug use (MDA) includes the general use of antibiotics in the population of the region, state, or country without the discrimination of people with or without the symptoms of infection

Human antimicrobial misuse or over-use

The term misuse or overuse of antibiotics in a human being is the practice of failure to complete the course of prescribed antibiotics and the use of antibiotics in treating viral infections, e.g. cold or flu, which do not respond to the antibiotics

Animal antimicrobial misuse or over-use

The antibiotics overuse/misuse in animals, especially animals in farming, refers to overuse or inappropriate use of antibiotics, which may be an improper use of antibiotics, i.e. to cure any diagnosed infection, use antibiotics to stimulate animal growth or to prevent disease caused by antibiotic resistance

Environmental contamination (including sewage and heavy metals)

Antibiotic wastes can contaminate the environment through manufacturing leftovers, the sewage system, and discarding inadequately, exposing the ecosystem to antibiotics, which lead to the emergence and transmission of antimicrobial resistance

Healthcare transmission

Healthcare associated drug resistant transmission involves the transmission of drug-resistant bacteria in the hospitals and clinics between patients or healthcare workers or contaminated surfaces. This is normally because of poor hygiene, over-crowding or a bad technique of using personal protective equipment, which plays a big role in healthcare-associated infection (HAIs)

Sub-optimal dosing, including from substandard and falsified Medications

Inappropriate use of antibiotics in humans is noted when the dose is either excessive or inadequate, and it is in many cases that it does not take into consideration the factors such as body weight, age, kidney functions. Dose errors of such a nature may make treatment less effective or encourage the emergence of resistant bacteria

Sub-optimal rapid diagnostics

The absence of effective and fast methods of diagnosis also interferes with the accurate and quick determination of whether an infection is viral, which frequently results in misuse of antibiotics, hence resulting in the emergence of antimicrobial resistance

Sub-optimal preventative medicine/vaccination

The main causes of infectious diseases spread are low vaccination rates and an inability to access the efficient vaccines. As a result, the under-immunization of individuals or the absence of vaccines means that the population-level protection diminishes, leading to spreading of the disease and more chances of antibiotic application and usually its improper use that contributes towards antimicrobial resistance

Travel

International mobility and the transmission of antibiotic-resistant pathogens: with increased global mobility, certain people can be carriers of drug-resistant bacteria without knowing it. This international mobility of resistant strains exacerbates the task of controlling infections and adds to the worldwide burden of AMR

 

 


This study analyzes current data to demonstrate how antimicrobial-resistant bacteria pose significant threats to health systems, economic stability, and environmental sustainability. It also emphasizes the urgent need for interdisciplinary and innovative AMR mitigation strategies to advance global health equity and support sustainable development.

 

Epidemiology of Global Antimicrobial Resistance:

The World Health Organization (WHO) scandalized with the increasing gravity of antimicrobial resistance (AMR) and the presumable post-antibiotic world in which common infections can be incurable. These data showed an encouraging picture of declining rates of resistant infections; however, in some countries the national surveillance data varied dramatically, perhaps due to underreporting. Resistance to fluoroquinolones has been reported in 92 countries, 3rd generation cephalosporin resistance in 86 which is almost always owing to extended-spectrum beta-lactamase (ESBL) production9. The same trends of resistance are observed with Klebsiella pneumoniae and methicillin resistant Staphylococcus aureus (MRSA). Surveillance systems all over the world, including the European Antimicrobial Resistance Surveillance Network and the national Healthcare Safety Network in the CDC, show that resistant infections have been on an ascent gradually over the last decade. A ratio of 10 to 30 per 100,000 individuals per year of Staphylococcus aureus and coagulase-negative staphylococci infections is seen in high-income nations as the most widespread Gram-positive infections. Despite the stabilization or worse in certain regions, resistant blood MRSA infections are still happening, especially with central nervous system and gastrointestinal responsive infections. Although most MRSA strains are still sensitive to trimethoprim sulfamethoxazole, glycopeptide resistance such as vancomycin and teicoplanin is on the increase10. The CA-MRSA has become an important public health concern as exemplified by five predominant clonal lineages that have occurred since the early twenty first century. Resistance E. coli belongs to the group of Gram-negative bacteria and is mainly attributed to CTX-M type ESBLs, that make penicillins and cephalosporins ineffective. The strains pose extra risk to immunocompromised patients, including patients with blood cancers. In the U.S. E. coli mediates approximately 8-14 percent of all bloodstream infections, and there is increasing resistance against aminoglycosides and quinolone. Klebsiella pneumoniae are also common ESBL producers, and are highly resistant against the third-generation cephalosporins11. It sprinkles the second most frequent species of carbapenem-resistant Enterobacterales. Even though there is generally low resistance to carbapenems within most EU countries, there is a great disparity with other countries such as Greece, Italy, and Romania, which have an even higher resistance rate to carbapenems12.

 

Mechanisms of Antimicrobial Resistance (AMR):

The effects of antibiotics are caused by interfering with vital bacterial processes which causes failure to grow or death of the bacteria13. As an example, β-lactams and glycopeptide affect the bacterial cell wall and membrane and weaken structural integrity. There are other types of antibiotics, e.g. linezolid, macrolides, chloramphenicol, tetracyclines, and aminoglycosides which exert their inhibition on the protein synthesis by bacteria. Rifampicin and fluoroquinolones disrupt synthesis of DNA as well as RNA creating defectiveness in replication of genes and transcription. Moreover, impairment in major bacterial metabolic pathways is modulated by polymyxins, sulfonamides, folic acid analogues and daptomycin14. Although they are normally initially susceptible, bacteria may adjust to antimicrobial assault using physiological shifts and become antimicrobial resistant (AMR) as illustrated in

Figure 115.

 

Figure 1: Mec hanisms of Antimicrobial Resistance (AMR). This figure illustrates how bacteria develop resistance through multiple mechanisms, allowing them to survive and multiply despite antimicrobial treatments15

 

Genetic Mutations:

Resistance may arise due to genetic mutations by bacteria which are spontaneous alterations that occur in the DNA of the bacteria. Such mutation may either change the structure or the functioning of the antibiotics target making the antibiotic less effective. As an example, in Mycobacterium tuberculosis, the RNA polymerase is the resistance-conferring mutation to rifampicin antibiotic, which blocks synthesis of RNA. The same can be said about mutation involving the gyrase gene that gives rise to fluoroquinolone resistance due to alteration in the replication of bacterial DNA16. Other mutations initiate the overproduction of efflux pumps which are proteins that secrete out the antibiotics before they could even operate on their target within the bacterial cell. It is a mechanism that enables bacteria to be resistant even in the presence of antibiotics. As an example, the Pseudomonas aeruginosa employs MexAB-OprM efflux pump to withstand fluoroquinolones, tetracyclines, and aminoglycosides17.

 

Horizontal Gene Transfer (HGT):

One of the most significant means through which antibiotic resistance gene (ARG) can be transferred between a bacterium and other bacterial groups is horizontal gene transfer (HGT). The process is what allows the quick response to antibiotic selective pressures by allowing the transfer of the resistance determinants among different species. There are three main mechanisms through which HGT takes place namely conjugation, transformation and transduction. Direct transfer of plasmids which are extrachromosomal DNA elements that harbor resistance DNA occurs in the conjugation process, and plasmids represent a traditional mechanism of spread of beta-lactamases in pathogens including Enterobacteriaceae, Pseudomanas spp. and Acinetobacter spp. As an example, blaNDM-1 gene that makes them carbapenem resistant is widely dispersed via conjugation. The process of transformation involves the acquisition of free, extracellular DNA by competent bacteria such as the case in Streptococcus pneumoniae taking in DNA fragments that have the penicillin resistance genes. The horizontally transferred resistance genes such as extended-spectrum beta-lactamases (ESBLs) can be mediated by transduction through bacteriophages (viruses infecting bacteria). A combination of these processes of HGT increases the rate of spreading of antimicrobial resistance and makes the treatment of infections problematic and in directions high-risks level18.

 

Enzymatic Inactivation of Antibiotics:

The resistance of antibiotics by bacteria is possible by large-scale enzyme production which destroys or alters them. As an example, the breakdown of penicillins and cephalosporins is done by beta-lactamases and carbapenems by utilizing carbapenem compounds in case of severe infections. Antibiotics such as gentamicin used against bacterial infections are modified by the action of aminoglycoside-modifying enzymes which prevent binding to the bacterial ribosomal proteins thereby inhibiting protein synthesis. Enzymes doing such actions contribute significantly to antimicrobial resistance (AMR)19.

 

Efflux Pumps:

Efflux pumps are proteins located on membrane which actively get rid of antibiotics into the bacteria prior to them taking effect. This component helps to contribute to multidrug resistance (MDR) as bacteria develop resistance to a number of different categories of antibiotics. An example can be given of Pseudomonas aeruginosa which employs the use of MexAB-OprM efflux mechanism to flush out fluoroquinolones, tetracyclines as well as aminoglycosides. Efflux pumps have a wide range of antibiotics that they can transport enabling bacteria to live in an environment of different antimicrobial agents. The Gram-negative and Gram-positive bacteria utilize this resistance mechanism20.

 

Altered Membrane Permeability:

There are some bacteria that may find a way around the metabolic ways as to which the antibiotics acts by use of used of different biochemical routes. As a case in point, trimethoprim prevents the activity of the enzyme dihydrofolate reductase that plays a really important role in synthesis of folate and DNA. Relatively, however, some bacteria will regulate and express other enzymes which allow the survival of the biosynthesis of folate in the presence of trimethoprim, thus avoiding its inhibitory situation. Through the use of these other metabolic pathways, bacteria will be able to thrive even when hit with antibiotics developed to interfere with their usual metabolic pathways21.

 

Population-specific risk factors recognised to AMR:

Other risk factors associated with antimicrobial resistance (AMR) also tend to be uneven due to the disparity of risk factors in developed and developing countries, and studies indicate regional gaps in methods used to counter them. In low-income countries and middle-income countries, AMR is mostly attributed to poor quality control of the drugs distributed, irrational use of antibiotics in the healthcare systems, limited surveillance structures, and regulatory deficiency in the distribution of antimicrobials. The percent of antibiotics sold under unregulated paths is relatively high and, in this case, there is a possibility of the pharmacies offering prescriptions on minor pathologies hence there is free access to the public. Such a great accessibility combined with low level of the citizens health literacy, a lack of understanding of the antibiotic resistance topic, and mistrust of the medication authenticity are contributing to some inappropriate uses of antimicrobials as well22. All these happen to increase the burden of AMR in such environments. Moreover, developing countries experience even more problems, such as uncontrolled antibiotics usage in healthcare establishments and wide prominence of antimicrobials in the agrarian environment. As an illustration, a report released in 2017 reported that China used 45 percent of all veterinary antibiotics in the world and is predicted to be the principal user through 2030. However, on the other side of the spectrum, the percentage of sales of antibiotics in relevant countries declined by 39.2 in the United Kingdom between 2015 and 2017, which is indicative of the increase of the antimicrobial stewardship in high-income countries. However, recent dynamics show that some of the factors that were characteristics of developing economies including inappropriate use of antibiotics, and weak regulation platforms are becoming prominent in the industrialized countries thus reducing the distinct boundaries of these countries23.

 

Ecosystem-Related Transmission Networks for Antibiotics:

Water Pollution:

Environmental microorganisms are known to manufacture natural antibiotics but their effect tends to be localized hence limiting their exposure. On the contrary, synthetic antibiotics with their broader impact form selection pressures on whole microbial communities. Some of the ways through which these antibiotics find their way into the environment include human excretion, and improper disposal; contamination by aquaculture or agricultural processes as well as wastewater of the manufacturing process of antibiotics24. Most of the antibiotics that enter the environment are based on their usage and excretion by human beings and animals. Antibiotics in the environment will depend on the concentration of the community-wide antibiotic use, the dose of the drug, and how the drugs are processed in humans and animal life. Assuming that the laboratory-derived values of Minimum Inhibitory Concentrations (MICs) are higher than the levels of the antibiotics in the environment, there still exist locations like the sewage treatment plants, whose levels surpass those anticipated to drive resistance25.

 

Veterinary and Livestock:

It has been established that animal wastes have the ability to release antibiotic-resistant bacteria and other pollutants to the environment. Like human beings, a good percentage (30 to 90%) of antibiotics that livestock takes in their bodies is released in their urine and feces. Some of the common antibiotics in animal wastes include tetracycline, flumequine, lincomycin, tylosin, oxytetracycline, doxycycline and sulfadiazine26. It has been detected that approximately one-third fecal samples have more than one kind of antibiotics and pig feces very likely have as high as three antibiotics and cattle feces, up to eight. Research has indicated that especially with reference to pigs, antibiotic resistance is able to transfer itself on the farms leading to environmental contamination27.

 

Manure and Sludge:

The common classes of antibiotics found in the sewage sludge wastes are less water-soluble and some of the common antibiotics that are found in the waste include ciprofloxacin, trimethoprim, sulfamethoxazole, doxycycline, and ofloxacin. Among the factors that influence the concentration of antibiotics in final sludge and compost, there is the origin of the wastewater, the applied treatment procedures, the properties of the antibiotics, and environmental factors28. Triclocarban and triclosan are biocides with antimicrobial (both bactericidal and fungicidal) activity commonly detected in the American sewage sludge, albeit on lower scales of up to 48.1mg/kg and 19.7mg/kg (dry weight), respectively. You also find antibiotics like azithromycin ciprofloxacin, ofloxacin, tetracycline, minocycline, doxycycline and the 4-epitetracycline and this is also quite common and, in most cases, they are within the limits of 0.8 to 6.8mg/kg (dry weight). Research indicates that such antibiotics and biocides are prone to absorb into the wastewater sludge and this feature sets them as being persistent in the environment29.

 

Impact of Antimicrobial Resistance on UN Sustainable Development Goals:

Antimicrobial resistance (AMR) is a pressing issue that significantly hampers progress towards achieving several of the United Nations' Sustainable Development Goals (SDGs). AMR, which occurs when bacteria, viruses, fungi, and parasites evolve to resist the effects of drugs, complicates global health efforts. It leads to prolonged illnesses, increased treatment costs, and more fatalities, undermining progress in achieving health and other SDGs30.

 

New Drug Development:

Antimicrobial resistance (AMR) has been increasing rapidly therefore, making the need all the more necessary to develop new antibiotics that will counter drug resistant bacteria. Scientists are always seeking alternative ways of curbing such infections. Teixobactin is a potential antibiotic developed in 2015, and its discovery comes after an attempt to develop a drug that targets drug-resistant organisms that cause trouble in the process of damaging the cell walls of the bacteria. The novel antibiotic, teixobactin, has a reduced chance of triggering resistance as compared to other conventional antibiotics. The other important news comes in the form of Lefamulin which was approved by the FDA in 2019 and it is used to treat the community acquired bacterial pneumonia, specifically the Pneumonia that is resistant to the old antibiotics. Lefamulin is an agent that binds to bacterial ribosome to shut down production of bacterial protein. The new antibiotic, zoliflodacin targeting Neisseria gonorrhoeae, inhibits the DNA replication process and can be an option to overcome the current problem of gonorrhea infections. Also, cefiderocol, a sort of cephalosporin that aids the uptake of iron by the bacteria, works on Carbapenem-resistant Enterobacteriaceae, and other antibiotic-resistant Gram-negative bacteria. The mechanism of action of this antibiotic makes it break the cell walls of bacteria and allow them to absorb iron, and it is a novel mechanism to combat AMR31,47.

 

Bacteriophages:

Bacteriophages are viruses, which attack and kill bacteria through breakdown of cell walls. Adapted lysins are enzymes made by these phages, and may be programmed to destroy particular bacteria, including antibiotic resistance strains. Lysins are easy to manufacture and have the ability to kill any kind of a variety of bacteria and provides urgent yet fast action in the event of bacterial infection, in particular, resistant bacteria. The sudden release of toxins can however be caused through the rapid destruction of the bacterial cells and may cause difficulties in the process of treatment. Use of bacteriophages in managing infections (phage therapy) has demonstrated success in some cases, especially in Eastern Europe, where it has a more than century-long history. However, there are still difficulties such as selection of suitable phages to use in specific infections, stability of phages, regulatory concerns and development of personalized treatment. Treatment combination with phage therapy has the potential to enhance the effect in phage-based treatment due to the individual mechanisms of action of phage therapy and antibiotics, antibodies or lysins32.

 

Combination Therapies:

A good way to result in better treatment results and avoidance of antibiotic resistance is the combination of several antibiotics that all address various levels of pathogen activity. The strategy assists in decreasing the selection pressure that usually deems to make a resistance. Well-known combinations are beta-lactams plus beta-lactamase inhibitor, such as ampicillin/sulbactam and piperacillin/tazobactam, which extend the activity of beta-lactam antibiotics by blocking the activity of beta-lactamases enzymes. The example of trimethoprim, and sulfamethoxazole (TMP-SMX) that prevents the bacterial folate synthesis in two primary stages by blocking dihydrofolate reductase and dihydropteroate synthase is another example. TMP-SMX shows impressive results in viral upper respiratory and lower urinary tract infections, opportunistic drug-resistant infections occurring in immunocompromised individuals, and both the drug-resistant Staphylococcus aureus (MRSA) and Pneumocystis jirovecii pneumonia. The use of combination therapies covers a wide selection of bacteria and allows slowing the evolution of resistance33.

 

CRISPR-Cas System:

The CRISPR gene-editing technology provides a fresh approach to affecting antibiotic resistance, hitting the target of the disabled resistance in the bacterial DNA. CRISPR has been used by scientists in designing artificial phages that act against the resistant bacteria and target those that have no resistance so as to make the current antibiotics effective once again. The same technology has been used in direct editing of the bacteria resistance conferring genes hence making previously resistant strains responsive to antibiotics34. Additionally, CRISPR has been used to produce synthetic peptides and protein as a method of creation that is aimed at occluding resistance routes in bacteria rendering them susceptible to the standard antibiotics. CRISPR is versatile and can be used to target specific resistance phenotypes including efflux pumps and enzymes that make antibiotics less toxic. Although methods based on CRISPR have challenges, such as precision and correct delivery, significant promise exists to use this approach as a method of promotion of antimicrobials and maintenance of the effectiveness of contemporary antibiotic applications35.

 

Antimicrobial Peptides:

Antimicrobial peptides (AMPs) are natural peptides with antibacterial properties, and have recently drawn interest as a potential new therapy of infections by a bacteria resistant to current antibiotics. The host defense AMP LL-37 exists in human tissues and body fluids and has been found to be effective in wound treatment and MRSA infections. Defensins are small cationic peptides which attack a great range of bacteria, both Gram-positive and Gram-negative stain. Naturally occurring peptides found in frogs and other amphibians are very much known to be able to destroy bacteria in many ways, and are known to be able to penetrate the cell walls of bacteria. Antimicrobial peptides have been demonstrated to work under various conditions, including in aquatic life, insects, and in the plant kingdom36.

 

Immune Modulation:

Immune modulation is a strategy employed to combat antibiotic resistance and it is defined as the process of ensuring the response to bacterial invasion and infection is heightened. Immunomodulatory pills such as interferons, interleukins and colony-stimulating factors are applied to stimulate macrophages and help to beat bacterial invaders. The emergence of vaccines which attack specific bacteria has been associated with less occurrences of antibiotic-resistant pneumonia. The immune system can generate increased numbers of white blood cells with the assistance of immunostimulants such as G-CSF, so fewer antibiotics will be needed. These measures help prevent bacteria and decrease the magnitude of dependence on antibiotics37.

 

Monoclonal Antibodies:

The evolution of monoclonal antibodies (mAbs) and antibody-derived products has enabled the writing of a particular and defining treatment to bacterial infections. Bezlotoxumab is directed against the toxin B of C. difficile and prevents the re-occurrence of infections in it, and Altastaph is directed against the surface protein of Staphylococcus aureus, and it neutralizes it. Attacking the usual composition of the cell wall of the bacteria, these antibodies also attack a broad spectrum of microorganisms. Lysibodies may decrease the need of highly specialized antibodies against each pathogen by being engineered to be specific against multiple species of bacteria. Antibody-conjugates which are a potential alternative to conventional antibiotics in the event of multidrug resistance Pseudomonas aeruginosa have also been researched and this process includes an attachment of antibodies with a toxic form38.

 

Nanoparticles:

Some of the benefits attributed to nanoparticle as antimicrobial agents are being wide-spectrum active agents, increased stability, and the ability that they have to enhance the solubility of poorly soluble antimicrobial agents. There is also a role of reducing antibiotic resistance with the help of them. Although this has its advantages, there are issues related to their compatibility with human cells, cost of production of the same, safety and environmental effects39. Metal-organic frameworks (MOFs) are unique in nature, in that they have crystalline structures and their antimicrobial potential is confirmed by the fact that they can be modified structurally and can also be used to release antimicrobial agents over time hence increasing efficacy and improving activity. Moreover, carbon quantum dots (CQDs) and carbon nanodots have diverse electric, optical, and chemical characteristics which allow them to attach with microbial cells, interplay with cellular membranes, and produce reactive oxygen species (ROS). These nano materials are non-toxic, enhance cell internalization and have potential in many spheres of biomedical applications40.

 

Heterocyclic Compounds:

Heterocyclic compounds, a broad concept of various chemical substances prepared out of other organic compounds in various methods of ways, are also becoming a potential avenue of antibacterial agents. These compounds are also helpful against wide range of bacteria that are both Gram-positive and negative. They make growth and survival very difficult because they have a way of disrupting critical life processes. There are two drawbacks of these compounds, namely the development of resistance and the problem of toxicity. More research is needed to ascertain their safety in clinical practice as well as address regulatory topics. Studies of the potential anti-infectious characteristics of antimicrobial peptides are underway41.

 

One Health Approach to AMR:

The One Health Approach is built on the premise that antimicrobial resistance (AMR) is an issue of global concern that requires a concerted effort by focusing on health linkage among human, animal and environmental health. Because of the rapid spread of AMR in human and animal populations, the process of managing infectious diseases is becoming ever more confused in various ways, including food chains, health care institutions, and the environment. Several multinational bodies have emphasized the role of collaboration at a sectoral level, and these include the world health organization (WHO), food and agriculture organization (FAO), the one health equine (OIE)34. Although the previous studies used to have an orientation towards human-centered factors, the current studies have received more concern regarding the role of animals as the key determinant. It is postulated that approximately over 73 percent of all the antibiotics in the world will be given to livestock, particularly those found in the food production sector. Controls such as prohibition of veterinary antibiotic use and specific doctor fees on the use of antibiotics as a way of controlling their abuse have also been suggested. As a result, bodies like the Responsible Use of Medicines in Agriculture Alliance (RUMA) are lobbying the sensible and responsible use of antibiotics to protect human and animal health and the farming sector has begun to develop antimicrobial stewardship schemes35. Nonetheless, such factors as poverty, insufficient healthcare infrastructure, corruption, and unhygienic sanitation systems precondition the implementation of the One Health Approach particularly in low-income countries and middle-income countries (LMICs) to be complicated. Moreover, with only a few alternatives to common practice of using antibiotics in treating serious bacterial infections in livestock, antibiotics are commonly used in animal farming in these native areas. Water, sanitation, and hygiene (WASH) programs Complementary interventions such as the improvement in water, sanitation, and hygiene (WASH) are important steps to increase the level of antimicrobial resistance management at low- and middle-income countries (LMICs), along with One Health programs42.

 

Epidemiological Surveillance in AMR Control:

A systematic review of observational data published in the recent past linking antibiotic use to emergence of MRSA resistance suggests that there is a lack of appropriate reporting in some of the studies.  One of the diagnoses made by the examination is the pressing need of high-quality epidemiological data representing all parts of the world and discussing high-risk groups to support the treatment selection process and expand the monitoring programs.  Some drug-resistant diseases do not have licensed therapeutics and hence the need to understand the mechanisms and forces that lead to antimicrobial resistance (AMR).  However, adoption of effective measures towards preventing antimicrobial resistance remains an issue of concern both in communities and hospitals due to lack of targeted therapies.  Epidemiological surveillance and recording of practices and use of antibiotics are very essential in setting up effective management of antimicrobial resistance in people and animals.  The study can help further discriminate high-risk groups who are mostly likely to be the carriers of resistant diseases.  Combining the data of both community and hospital interventions, the electronic health records, pathogen tracking, and clinical records are vital to the improved management of antimicrobial resistance.  Although the data exists, there are no common processes of data gathering and analysis of resistance.  The dynamic effects of antimicrobial resistance (AMR) on people, livestock, and ecology have cross-related aspects that require a more governmental system of data collection.  Routine antimicrobial resistance surveillance through standardized procedures and prompt sharing of data is pivotal towards having accurate sources and patterns of antimicrobial resistance in humans, animals and through the food chain.  Enhancement of the knowledge on pathogen lineages across different populations aided by the technology of sequencing is crucial in strengthening antimicrobial resistance surveillance and control programs44.

 

Antimicrobial stewardship programmes (ASPs):

Antimicrobial Stewardship Programs (ASPs) are aimed to reduce the emergence and spread of antimicrobial resistance (AMR) through rational and evidence-based treatment using antibiotics. Such programs often embrace the use of electronic health record (EHR) systems to standardize the administration of antibiotics prescribing as per the laid down procedures. EHR systems also encourage review of microbiological results within 48 or 72hours and enable better decision making on the antimicrobial treatment regimens continuation, adjustment or discontinuation45. Also, surveillance software can streamline the choice of antibiotics by informing prescribers on the optimum prescription. The deployment of ASPs requires access to effective ecological and epidemiological data on AMR. Research has established that, despite the large initial cost on adopting ASP through conducting training personnel, the programs have been found to be cost effective both in the medium and long-run, even in low resource environments. Coupling of complementary measures like intensive hand hygiene practices also boost the effect of the AMR mitigation strategies46. Precision medicine can be an effective pathway in counteracting AMR because precision antimicrobial therapies will be customized to the patient profile based on susceptibility to infection as well as responses to treatment; the effectiveness of this approach depends on the presence of rapid, accurate and cheap diagnostic services. The urgent need of new antimicrobial agents to deal with the drug resistance of pathogens is still present since there are no new classes found since the year 1987. To succeed this endeavor, academic researchers, pharmaceutical industries and governmental bodies will need to work in sync47,48.

 

Prevention and treatment:

The antimicrobial resistance (AMR) is an important issue in low- and middle-income countries (LMICs).  Its effects can be relieved by preventive measures such as immunization, strict food safety policies, infection control measures, and improved waste management49.  However, a few LMICs face a number of challenges, like the lack of healthcare infrastructure facilities and shortage of healthcare personnel that make the implementation of these efforts difficult.  One of the major steps taken in countering AMR is the development of rapid diagnostics that can be used to detect infection by bacteria and resistance to antibiotics simultaneously.  The behavior of using an antibiotic depends on different factors that change the trends in different settings such as the prevalence of self-diagnosis, popular use of over-the-counter medications, and local prescription regulations.  Poor use of antibiotics and lack of point of care diagnostic methods promotes growth of resistant microorganisms. In addition, undereducated patients could prematurely stop using medication, thus worsening resistance50.  Globalization through increased mobility of populations has increased the spread of resistant diseases and it has been pointed out that widespread global surveillance systems are needed to track the danger posed by imported drug resistant bacteria.  Newer technologies such as next-generation sequencing present opportunities in understanding the source of antimicrobial resistance (AMR) as well as demystifying the role played by population movement in its distribution.  In addition, the possibility of development and transmission of antimicrobial resistance may increase with urbanization in low- and middle-income nations.  The multi-sectoral approach to combating AMR in these countries involves involving the interest of international stakeholders in carrying out effective and sustainable intervention measures51,52.

 

CONCLUSION:

The development of antibiotic-resistant microbial life forms is destroying the efficiency of modern therapies used to battle diseases of infection and is also a very serious global health danger. The problem is made even worse by the usage of antibiotics poorly and effective infection prevention methods that are not adequate as well as suboptimal surveillance systems in low- income countries and middle-income countries. The essential precondition concerning the elaboration of the effective diagnostic and interventions strategies based on antimicrobial resistance (AMR) is a profound comprehension of the factors and molecular pathways involved in the process. Avoidance, such as vaccination, stewardship of antimicrobials, and an increased focus on sanitation, ought to be a priority to restrict the spread of resistant pathogens. At the same time, it is important to continue the development of new antimicrobial agents and rapid diagnostic technologies. A situation of AMR is more than a clinical issue but it is a shared global responsibility. Unless communities, medical workers, policy-makers, and researchers organize timely and coordinated action, the achievements made in healthcare may be discarded and the surrounding environment will be swept with the high rates of morbidity, death, and costs of healthcare. The future generation can only have sustainable solutions to equitable healthcare if they preserve the efficacy of the antimicrobial agents.

 

Abbreviation:

AMR = Antimicrobial Resistance

ASP = Antimicrobial Stewardship Programs

ASPs = Antimicrobial Stewardship Programs

EHR = Electronic Health Record

ESBLs = Extended-Spectrum Beta-Lactamases

FAO = Food and Agriculture Organization

HAIs = Healthcare-Associated Infection

LMICs = Low- And Middle-Income Countries

MDA  = Mass Drug Use

MRSA = Methicillin Resistant Staphylococcus Aureus

OIE = One Health Equine

RUMA = Responsible Use of Medicines in Agriculture Alliance

SDGs = Sustainable Development Goals

TMP = Trimethoprim

WASH = Water, sanitation, and hygiene

 

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Received on 28.07.2025      Revised on 12.11.2025

Accepted on 26.01.2026      Published on 20.05.2026

Available online from May 25, 2026

Research J. Pharmacy and Technology. 2026;19(5):2397-2406.

DOI: 10.52711/0974-360X.2026.00343

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