INTRODUCTION:

Introduction to Antimicrobial Resistance (AMR)

AMR is an urgent threat to public health and one of the greatest dangers to global health security over the last century, threatening not only global health but also development and productiveness of governments and organizations. AMR is defined as the property of microorganisms, bacteria, viruses, fungi, and parasites to become refractory to the effects of drugs that previously treated these diseases effectively. The consequences of this refusal are manifold and severe, especially at the individual, community and national level, on all regions and income levels¹. The idea behind this section is to explain the extent, causes, and implications of AMR with a view to giving background to a multidisciplinary and holistic approach to the AMR challenge. It is no longer the problem at a distance or the hypothetical problem, but the one that is imminent and measured. In the ensemble analysis published in The Lancet, the direct cause of death associated with bacterial AMR in 2019 was estimated to be about 1.27 million cases and an all-cause 4.95 million deaths were found to be linked to bacterial AMR. These figures highlight the imminent threat of resistant infections, which make ordinary treatments ineffective and lead to a long-term disease, high healthcare expenditures and mortality. With the loss of effectiveness of antimicrobials, even such basic medical practices as surgery, cesarean section, and chemotherapy will be extremely risky to patients, posing a huge burden to the medical facilities all over the world².

The global misuses and overuse of antimicrobials are some of the key amplifiers of AMR in both human and veterinary medicine, agriculture, and animal rearing. Clinical application of antibiotics Since the 1920s, the antibiotics have been widely used in clinical medicine i.e., they are often prescribed and improperly used in the clinical practice because they are used to treat viral infections which cannot be treated by the antibiotics³. Meanwhile, in the livestock businesses and agriculture, they use the antimicrobial as growth stimulators and disease prophylaxis. These are some of the practices that subject it to evolutionary pressure, promoting the emergence and distribution of drug-resistant pathogens. This ecological aspect of AMR illustrates that the issue has its origins in our food production, as well as public health systems and thus needs to be dealt with on a cross-sectoral level through the One Health approach, which is focused on connections between human, animal, and environmental health⁴.

MR is a purely global issue and goes across countries of all income levels. Yet, its burden is highly concentrated in low- and middle-income countries (LMICs), and their healthcare infrastructures, rules and regulations, or even awareness might be low to address the crisis optimally. These areas are frequently under served by quality diagnostics, skilled health care providers, and current treatment recommendations and it is very easy to overuse and underutilize antibiotics. In addition, there is a poor sanitation, inadequate access to clean water, and insufficient infection-preventing measures that lead to increased disease burden, hence driving increased antimicrobial usage. It is not only that poverty and inequality contribute to the spread of infections that are resistant to treatment, but that they also exacerbate the outcomes creating a vicious cycle, which diminishes global economic development⁵.

Intimidation associated with AMR does not only affect the health outcomes of individuals but also threatens across-the-board advancements of modern medicine that have been achieved over decades. The possibility of carrying out procedures associated with the use of effective antimicrobial prophylaxis and post-operative control of infections is threatened. As an example, some simple surgeries cannot be performed without reliable antibiotics, which will make the surgery life-threateningly complicated. Antibiotics are needed in cancer patients whose immune systems are weak during treatment to prevent and cure secondary infections. The scope of MR shadow thus spreads over a broad base in terms of therapeutic interventions and can negate health benefits of vaccination, hygiene and inventions in the field of public health. Besides having significant health consequences, AMR can have significant economic cost to any society. According to the World Bank, it is expected that the costs of AMR to global healthcare costs will be up to US$ 1 trillion by 2050. Also, it would decimate total worldwide gross domestic product (GDP) of up to US$ 3.4 trillion every year by 2030 as a result of decreased labor productivity, faster death rates as well as growth in economic inequality. Such projections indicate that a coordinated and international effort must be put in place to avert the situation in which economic prosperity may be destroyed by an out-of-control resistance crisis. The costs of healthcare will not only burden the government but also the households and individuals who may experience disastrous healthcare expenditures. The realization that the antibiotics research and development (R&D) pipeline is increasingly broad has also become one of the most important things to come out of efforts to combat AMR. Although the threat of resistance is rising, there has been little medicine produced in the pharmaceutical industry to combat antibiotics largely because of the poor returns of investment as opposed to chronic conditions drugs. The end result of this is that very few new antimicrobial agents are actually in a pipeline and that those which are, are not usually available to those people and countries who most need them. This brings about the twin crisis of innovation and access. In response to such a gap, new products in the form of antibiotics, vaccines, and diagnostics need to be developed due to the urgent need of investing into R&D, and existing products should be distributed fairly and utilized correctly. The solution to AMR should be multifaceted and coordinated to combat the problem in human health. Prevention of infections is a priority because it would mean that there will be fewer antimicrobials required in the first place. Increasing the rate of vaccination, improving hygiene and sanitation, and reinforcing IPC measures in health care facilities, etc, are essential measures. It is also relevant to provide access to high-quality diagnostics and suitable treatment of bacterial infection so that all patients can receive them and that can reduce the abuse of antibiotics and improve person outcomes. The increase in laboratory capacities, education of the healthcare professionals, and inclusion of diagnostic stewardship as a part of the clinical workflow are some of the key elements of this strategy⁶.

Figure 1: Key Antimicrobial Resistance Mechanisms and Major Resistant Pathogens

The global response also considers strategic information, surveillance and innovation to be central. The surveillance systems that monitor AMR trends and antimicrobial consumption serve to advise policies at the national and the global level and facilitate quick responses to the emerging AMR threats. The World Health Organization has its Global Antimicrobial Resistance Surveillance System (GLASS) that stands out as one of the attempts to normalize and centralize resistance data registration. At the same time, there is potential in new therapeutics, such as non-standard procedures, including bacteriophage therapy and antimicrobial peptides or microbiome restoration, as strong alternatives to regular resistance processes. To summarize, antimicrobial resistance is a serious and, on the increase, crisis straddling the areas of medicine, food or crop production and the economy along with development of nations or communities. The threat is multifaceted and has deep roots in systemic challenges including inequality, inaccessibility to care, and unhealthy drug consumption. The solutions to the AMR problem have to be cross-disciplinary, global, and focused on preventing it, with equal access to healthcare services, medical research, and political will. Once we reel in exactly how AMR established within the pharmaceutical sector and how it is expanded⁷, we will be able to develop durable, sustainable solutions to guarding human health and well-being over the coming millennia.

Global Epidemiology and Burden of AMR:

The epidemiology of AMR across the globe has changed significantly over the past two decades, and today, MDROs are classified as a serious public health issue. Health system and non-systemic disparities, antimicrobial misuse, and environmental factors cause significant regional variation in resistance rates, according to surveillance data from the World Health Organization Antimicrobial Resistance Surveillance System (GLASS) and other organizations in the region⁸. The Southeast Asia and Eastern Mediterranean regions have some of the highest rate of incidences of resistance especially to the last-line antibiotics. Europe European-wide surveillance by the European Centre for Disease Prevention and Control (ECDC) records an increasing trend across Europe with respect to Klebsiella pneumoniae-resistant to third-generation cephalosporins, fluoroquinolones, and aminoglycosides - again with the greatest acuteity in the south / east. The problem of ESBL producing Escherichia coli and Klebsiella spp. has increased in Latin America both in the community and the healthcare setting. The Sub-Saharan Africa is the most susceptible region because of laboratory infrastructure and lack of surveillance⁹. Nonetheless, multicentre research reports depressingly high drug resistance among such pathogens as Salmonella, Shigella and E. coli, especially in paediatric bloodstream cases. In contrast, stabilization or even reductions have been observed in methicillin-resistant Staphylococcus aureus (MRSA) in high-income countries since 2015, although the incidences of carbapenem -resistant Enterobacteriaceae (CRE) infections (particularly intensive care units) are on the rise.

LMICs are grappling with the highest problem of resistance to first line antibiotics with over 50 percent resistance being recorded in most places. The resistant infections were mainly local by 2012 but starting in 2013, it has taken an endemic distribution trend. The international dissemination of resistance genes like New Delhi metallo-beta lactamase (NDM) and mobilized colistin resistance (mcr) are recent global problems that have contributed to the dire situation of resistance in a very significant way since they can spread rapidly due to international travel and trade. Based on epidemiological evidence, the most at-risk groups are the weak populations¹⁰, such as elderly people, immunocompromised individuals, and children in LMICs. The rise of MDRO infections in communities is beginning to grow severely since 2018, especially in highly populated urban regions. Healthcare workers have also become a source of MDRO transmission reservoir, with colonization rates of between 6 to 45 percent the world over.

In addition to the clinical implications, AMR has significant economic implications. It has been reported that direct healthcare expense connected to resistant infections has increased by 45 percent since 2020 due to extended hospital admissions and more intensive treatment. In 2023, alone, the United States could find the additional spending on healthcare that is related to AMR and account to USD 4.6 billion. Morbidity and mortality due to AMR cost the global economy an estimated USD 88 billion every year¹¹. The agricultural sector is no exception, and food animal infections that are resistant to medications have lowered productivity by 12 percent. Moreover, high costs of doing R&D, and low returns discourage pharmaceutical innovation. The international pipeline of novel antibiotics is thin, specifically against Gram-negative pathogens, much like Pseudomonas aeruginosa and Acinetobacter baumannii. There is a chance that without more substantial investment, the threat of infections that could not be treated will rise¹². That is why overcoming AMR will involve harmonized surveillance globally, equal access to diagnostics and medicines, and the enhancement of the stewardship in all the sectors.

Socioeconomic and Environmental Determinants:

Antimicrobial resistance (AMR) is not only a microbiological issue but the particular issue is highly imbibed in the socioeconomic and environmental factors that drive the use and the trends of antibiotic resistance. Prescribing behavior is one of the important factors, and its patterns differ considerably in various healthcare settings. Research indicates that 30 to 50 percent of prescribed antibiotics to outpatients are inappropriate or unnecessary, and this is attributable more to diagnostic uncertainty and the unavailability of rapid diagnostic capabilities. Although antimicrobial stewardship programs (ASPs) have been identified to have potentials in the optimization of antibiotic utilization, their implementation tends to be effective depending on the power and the nature of the local healthcare systems. Within long-term care facilities, certain prescribing characteristics have resulted in heightened rates of resistance development to represent the role that institutional practices play in resistance¹³. The lack of strict measures and the great susceptibility of the patients make such environments hotbeds of abuse and resistance organism spreading.

Agricultural antibiotic use is another force behind AMR. Livestock growth promotion and disease prevention by using antimicrobials is common in areas where there are lax regulations. Recently, direct effects of agricultural antibiotic usage on resistance dynamics in human pathogenic organisms have been quantified. This is further complicated by environmental contamination wherein antimicrobial production residues of pharmaceutical manufacturing in healthcare facility, and agricultural runoff triggers the entry of the resistance genes to water hence forming an environmental reservoir of resistance genes. Poor management of industrial waste has also been associated with the development of resistant organisms in rivers and soil, which makes the natural ecosystems conditions of AMR breeding places. There is another complexity given by the climate change scenario¹³. Temperature modification, humidity, and water quality also change bacterial survival rates and mode of transmission, indirectly creating conditions conducive to resistance emergence, and continuance of genes within natural reserves. Perception and behavior of the public play a crucial role in the trend of AMR. The misuse is enforced by misconceptions on antibiotics, self-medication and the easy availability over the counter, common in many low and middle-income countries. The patterns of consumption of antibiotics are also influenced by cultural norms, behavior related to seeking healthcare, both former factors affecting people in specific communities that do not seek professional healthcare and prefer informal health services or self-medicate. Moreover, social media and internet-sourced information have increasingly contributed to the development of attitudes towards the usage of antibiotics, which often contains misinformation that promotes the wrong usage.

Economic differences are also of great importance. In resource-limited locations, the inability to access healthcare and diagnostics results in empirical treatment or inappropriate use of poor-quality or fake medicine. The economic burdens can cause patients and other medical providers to engage in prescription abuse or drug-seeking activity. Such determinants should be combated in a complex way¹⁴. The message of the campaign involving public education should be geared towards particular cultures and socioeconomic backgrounds to eliminate such misconceptions and aim at encouraging responsible use. In a clinical setting, ASPs with advanced diagnostic support tools, supplementary feedback mechanisms, and evidence-based guidelines are highly important. mHealth and electronic decision-support systems have the potential to improve the prescribing practice in underprivileged regions. Furthermore, there is a potential to have fair access to good-quality antibiotic and diagnostics through public-private partnerships. The key aspect of a truly comprehensive and sustainable response to the AMR crisis is embedding all of these efforts in a One Health approach, which combines the concept of human, animal, and environmental health.

AMR and the Sustainable Development Goals (SDGs):

Antimicrobial resistance (AMR) is not merely a serious problem in the field of public health but also a myriad of impediments in the execution of the United Nations Sustainable Development Goals (SDGs). As costly as it is to individual health, AMR is becoming a major threat to global health because it further destroys all that has been achieved under its various targets and agendas. Vested with the sense of urgency, the World Health Organization (WHO) made the declaration of AMR as a worldwide issue in 2014, and the Global Action Plan has insisted that there needs to be national responses by 2017. Incorporation of AMR control into SDG framework is important to ensure that successful development is achieved¹⁵. The scope of MR is the point of intersection with SDG 3 (Good Health and Well-being), which envisages improvement of healthy lives and well-being of all. MR resistant compromises our capability to address infectious illnesses and threatens decades of healthcare development and intensifies the number of morbidity and fatalities, specifically in vulnerable communities. Antimicrobial stewardship (AMS) programs are among the effective measures to minimize the use of unnecessary antibiotics and enhance better patient outcomes. Nations that have adopted AMS including via the WHO- and UN-recommended initiatives show advancements in both the safety of patients and the economic viability.

MRs are also a threat to SDG 6 (Clean Water and Sanitation) and SDG 12 (Responsible Consumption and Production). Resistance antibiotic residues in the environment are also widely released, due to pharmaceuticals, agriculture, and waste water. Addressing these links requires the One Health approach in which health conditions in people, animals, and the environment are not treated separately. The Quadripartite (WHO, FAO, UNEP, and WOAH) stresses the wide ecological implications of AMR and promotes environmental factors such as multi-sectoral collaboration that could control its proliferation¹⁶.

The success of AMR initiatives also sustains SDG 17 (Partnerships in the Goals). Of course, there are already examples of international collaboration like the Tripartite FAO/OIE/WHO and the Global Alliance on Rapid Diagnostics (GARD). The network to the network (NTN) model of GARD encourages both training and research and development in different regions and increases the richness of testing as well as scientific neutrality between low- and high-income countries¹⁷. Digital and big data are also one of the emerging elements in AMR mitigation, finding a place within SDG 9 (Industry, Innovation, and Infrastructure). Real-time surveillance systems and AI-driven diagnostic tools increase the ability to detect as early as possible and provide more personalized treatment options in resource-limited settings. The technologies have a positive effect by promoting access to and the quality of decision-making, prevention of misuse of antimicrobials, and development of novel treatment¹⁸. AMR poses challenges to the achievement of a number of SDGs, due to the problem aggravating health disparities, environmental impairment and economic burden. The fight against AMR needs to be global, interdisciplinary, and would involve involving technological, education, and policy innovations. AMR is also a health goal that is not only important in and of itself, but is also firmly entrenched within the 2030 Agenda on sustainable global development.

One Health Approach to Tackling AMR:

Antimicrobial resistance (AMR) is a global health burden that has become a live threat and the infections caused by multidrug-resistant bacteria have rendered all existing treatments as ineffective; causing increased mortality and financial burden. All this time, WHO has reminded the world that, unless we alter the pattern of the current use of antimicrobials, new drugs would soon get ineffectual. The international, multisectoral nature of the problem is at the heart of the One Health approach which acknowledges the human, animal and ecological health relationship¹⁹. The problem with MR is spurred by the overuse and misuse of antimicrobials in all sectors. Antimicrobials in agriculture are widely used, not only in treating sick farm animals, but also as growth promoters and for prevention of diseases often in inappropriate ways. The excretions of such drugs into the environment pollute soil and water and are part of the resistant bacteria spreading to other ecosystems. Unfortunately, quite a number of the same categories of antimicrobials are crucial in usage with human medicine and are also applied with the same classes in animals, plants, and aquaculture, which increases resistance all around living domains. To tackle these risks, the international bodies, namely WHO, the Food and Agriculture Organization (FAO), and the World Organization for Animal Health (WOAH) have collaborated with the creation of the Global Action Plan on AMR. In this plan, AMR surveillance and responsible use of antimicrobials are encouraged across sectors. The Global Antimicrobial Resistance Surveillance System (GLASS) started in 2015, aiming to create a standardized data that is globally collected on consumption and resistance of antimicrobials in humans and animals. This scheme aids in the detection of trends, as well as monitoring the dissemination of resistance gene in various environments. An important component of the One Health action plan also involves minimizing inappropriate use of antimicrobials in agricultural production and fish farming, better infection control and sanitation in hospitals and clean-up of wastes to prevent environmental pollution. The World Antimicrobial Awareness Week is one of the ways to help professionals and laymen learn how to act reasonably using antimicrobials²⁰.

The investment in research and innovation is equally important. The ease of rapid diagnostic tools development will reduce inappropriate and incorrect diagnosing and incorrect prescripts. Vacines, phage therapy and other alternatives are giving hope that we can reduce antibiotics dependence. Global alliances such as the Global Alliance Antibiotic Research and Development have been making progress towards finding new products that will work against WHO priority pathogens. The issue of better governance and cooperation that the One Health approach proposes is also more important. A concerted global action by policy, healthcare professionals and workers, veterinarians, environmental scientists and communities is required to incorporate and ensure sustainability of effective measures. The next important things are the development of human resource capacity in controlling infectious diseases and provision of incentives to pharma innovations. In brief, the One Health approach is realistic in identifying that the potential solution to AMR cannot be addressed by one sector²¹. By improving community awareness of the interdependence of ecosystems, encouraging inter-sector cooperation, and facilitating sustainable transition, it offers the most extensive route to mitigating the AMR epidemic.

Innovations and Strategies to Combat AMR:

New antimicrobial resistance (AMR) in the world requires the implementation of new approaches that go beyond traditional antibiotic research. The cellular processes that are important to traditional antimicrobials are DNA replication (quinolones), RNA and protein synthesis (aminoglycosides), cell wall production (beta-lactams, vancomycin). and membrane stability. Nonetheless, there is growing resistance to these agents, which has been driving scientists to devise new research areas in the area of antimicrobial discovery and design. Among the least expected solutions, but at the same time promising ones, may be the use of new antibiotics found in nature. Soil microbe, marine, and plant extract natural products continue to be a fertile source of bioactive molecules²². The bioinformatic tools and genome mining allow this effort to be more supported and aid in biosynthetic gene clusters identification which would encode novel antimicrobial metabolites. More modern approaches place an emphasis on eliminating the viability of bacteria and also using virulence and metabolic certain pathways. Avirulence factors (e.g., secretion systems or quorum sensing) can be perturbed by compounds which are not associated with a selective force that drives resistance like their counterparts, antibiotics. The further enhancement of the discovery of context-effective drugs is host-adapted screening methods that can also evaluate compound efficacy in a condition reproducing the host environment. The field of drug discovery has also been transformed with machine learning and artificial intelligence predicting antimicrobial activity and the optimization of molecular docking of target-specific compounds. The computational strategies are employed to virtually filter databases of small compounds based on their potential to interact with proteins of bacteria, such as persistence-related and even some biofilm-associated proteins.

Combinatorial therapy is another potential strategy and existing drugs are screened to see whether there are synergistic effects. The technique also does not only activate the effectiveness of the old antibiotics but also decreases the chance of the development of resistance due to the simultaneous strike of alternative targets in cells. Intrinsic mechanisms of resistance are also discovered in a better way that provides new targets in drug development. As an example, targeting the resistance mechanisms like muramyl endopeptidases in Salmonella typhimurium has made the pathogen sensitive to vancomycin²³. Also, Derivatised 2-lactam, especially N-thiol substituted monocyclic compounds, have been found as having the ability to inhibit enzymes like L-D transpeptidase 2 in Mycobacterium tuberculosis and testifies effective in both dormant and multidrug-resistant bacteria. Another new strategy is going after horizontal gene exchange. Low doses of antibiotics have been known to increase transfer of plasmid-mediated resistant resistance in bacteria. Concerted efforts to prevent plasmid maintenance/conjugation²⁴, as observed with IncFIA plasmids may have the potential to make further dissemination of resistance genes much more difficult; particularly in the event that such targeted strategies are specific to resistance related plasmids in resident flora.

Lastly, structure guided drug design- through the use of protein crystallography and in vitro screening, specificity and efficacy can be achieved by refining and optimizing a compound. The techniques permit the redesign and repurposing of existing compounds in order to get through resistance connected with changed or homologous bacterial targets. To sum up, the problem of AMR needs a multidimensional solution that includes the creation of natural compounds, computational models, high-throughput screening, and genetic knowledge²⁵. Combined with solid public health measures, such innovations give a chance of a sustainable and successful containment of AMR.

Future Directions and Research Priorities:

Innovative, Integrated and Equitable solutions are the key focus of future research regarding the antimicrobial resistance (AMR) and its worsening around the world. The advent of resistant pathogens demonstrates the necessity of something drastic in order to step in because such pathogens like E. coli with more than 60 percent resistance to the third-generation cephalosporins in South Asia, and Klebsiella pneumoniae with more than 50 percent resistance to carbapenems in Eastern Europe are strong indicators of the need to take action. Although scientific innovations are fast-growing, there is a wide disparity in the translation of research to practice, more so in resource-constrained environments. New treatment methods are on the rise Risper-based technologies may hold potential in the accurate targeting of resistant species of bacteria and provide the ability to offer highly specific and adaptable treatment strategies²⁶. The same thing happens with bacteriophage and immunomodulatory treatment: both have re-appeared as alternatives to other more common antibiotics. There is a lot of potential with the manipulation of the human microbiome in order to stop colonization by a resistant strain. Such methods need sound clinical validation, an ethical review system, and the current system of delivery to be scalable.

Artificial intelligence (AI) is also revolutionizing the AMR field by allowing quick discovery of an efficacious drug, refining treatment regimens and anticipating resistance patterns. Surveillance can be improved using machine learning with the combination of genomic, clinical, and epidemiological analysis. In the meantime, nanotechnology and advanced drug delivery agents are being formulated to provide better antimicrobial activity and reduce development of resistance. Multiplexed large-scale signal detection systems such as those using quantum sensing have the potential to provide resistance-markers detection hundreds of times faster and higher sensitivity than currently achieved, allowing targeted treatment of cancer to commence immediately. Nonetheless, implementation is not uniform. Whole-genome sequencing (WGS) has been implemented by 35 percent or fewer of WHO member states in their AMR surveillance, which constrains the ability to monitor the evolution of resistance in real-time. In addition, although the technological capacity has increased²⁷, very little money is spent on AMR innovation, which is less than 1% of the overall spending on health research and development. This bifurcative profile should require fund reallocations, regularization of home scan, and the formation of common platforms of data in order to conjoin discovery with deployment. Another research priority is the need to understand how resistance is transmitted through the human, animal and environmental ecosystems. The One Health concept should become a part of the future policy and research programs. Behavioral, cultural, and socioeconomic studies on antimicrobial use, especially of the LMICs, would be paramount in distributing effective stewardship programs. Unless these human aspects are considered, even the high tech will not see much adoption. With regard to economic planning, new models that can provide incentive to develop sustainable antibiotics and make them accessible to all must be developed²⁸. There must be push n pull mechanisms like market entry incentive or subscription-based systems but they need to be designed to promote pharmaceutical investment that is not prohibitively costly to low-resource health systems. Above all, there should be better global coordination. Adoption of emerging technologies in healthcare systems, and in particular in LMICs requires contextual implementation practices. International frameworks have been elevated to respond to cross-border resistance threats and enhance surveillance coverage and decrease disparities in data among the high-income nations and the global south. Overall, addressing AMR demands a synergetic response, which can be performed via a combination of biomedical innovation, digitization, social-behavioral sciences²⁹, and inclusive policymaking, to provide a sustainable and global response to one of the most severe challenges of our era public health-wise.

CONCLUSION:

There is a heavy burden of antimicrobial resistance (AMR) threatening the world health and disproportionately affecting the low- and middle-income countries. The increase in the rates of resistance caused by misuse, lack of surveillance, and socioeconomic inequalities counters the objectives of modern medicine and sustainable development. Multidrug resistant organisms are spreading globally and need to be controlled with immediate effect in human, animal, and environmental health development. The problem of AMR needs a holistic approach to it, which includes improved surveillance, fair access to diagnostics and therapeutics, prudent antibiotics consumption, and innovation efforts. There is no doubt rather that as long as there are no immediate, coordinated and sustainable solutions that are based on One Health approach, the global health and economic burden of AMR will keep growing.

REFERENCE:

1. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399(10325): 629–55. doi:10.1016/S0140-6736(21)02724-0

2. Earny VA, Kamath V, Muralidharan A, Vandana KE, Khera K. Marine Microbial Metabolites: A new wave of drugs for Combating Antimicrobial Resistance. Res J Pharm Technol. 2021; 14(4): 2348-52. doi:10.52711/0974-360X.2021.00414

3. Abbas HA, El-Saysed MA, Ganiny AM, Abdel Fattah A. Antimicrobial Resistance Patterns of Proteus mirabilis isolates from Urinary tract, burn wound and Diabetic foot Infections. Res J Pharm Technol. 2018; 11(1): 249–52. doi:10.5958/0974-360X.2018.00046.X

4. Abbas HA, El-Sayed MA, Al-Kadi LM, Gad AI. Diabetic foot infections in Zagazig University Hospital: bacterial etiology, antimicrobial resistance and biofilm formation. Res J Pharm Technol. 2014; 7(7): 783–8.

5. Rani U, Chawla K, Lewis LE, Bairy I, Kumar S, Muragundi PM. Antimicrobial Resistance and Microbiological Spectrum among Neonate Acquiring Healthcare-Associated Infections in South India. Res J Pharm Technol. 2022; 15(12): 5647-50. doi:10.52711/0974-360X.2022.00952

6. Sreeja MK, Gowrishankar NL, Adisha S, Divya KC. Antibiotic Resistance-Reasons and the Most Common Resistant Pathogens – A Review. Res J Pharm Technol. 2017; 10(6): 1886–90. doi:10.5958/0974-360X.2017.00331.6

7. Zine S, Patankar SA, Raopati SS. Rise of Antibiotic Resistance in Tuberculosis. Res J Pharm Technol. 2018; 11(7): 3201–4. doi:10.5958/0974-360X.2018.00588.7

8. Marino A, Maniaci A, Lentini M, Ronsivalle S, Nunnari G, Cocuzza S, et al. The Global Burden of Multidrug-Resistant Bacteria. Epidemiologia. 2025; 6(2): 21. doi:10.3390/epidemiologia6020021

9. Patel SK, Roberts JA, Lipman J, Tängdén T, Harbarth S, Winterfeld U, et al. Antimicrobial resistance in low-income settings. Lancet Glob Health. 2024; 12: e45–57.

10. Martinez JL, Coque TM, Baquero F, Canton R, Rossolini GM, Pascual A, et al. Novel resistance mechanisms in gram-negative bacteria. Nat Rev Microbiol. 2024; 22: 89–102.

11. Morgan DJ, Laxminarayan R, Duse A, Wattal C, Zaidi AK, Wertheim HF, et al. Economic burden of antimicrobial resistance: A global perspective. Health Econ Rev. 2024; 14: 12–25.

12. Goldman RD, Coast J, Smith RD, Miller E, Laxminarayan R, Mendelson M, et al. Global economic impact of antimicrobial resistance. World Dev. 2024; 164: 106118.

13. Anderson MJ, Fridkin SK, Pollack LA, Srinivasan A, Laxminarayan R, Suda KJ, et al. Patterns of antimicrobial prescribing in global healthcare settings. Clin Infect Dis. 2024; 78: 234–47.

14. Ramirez JA, Musher DM, Evans SE, Dela Cruz CS, Crothers KA, Hage CA, et al. Impact of rapid diagnostics on prescribing decisions. Diagn Microbiol Infect Dis. 2024.

15. Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Aguilar GR, Gray A, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399(10325): 629–55.

16. Payumo J, Alocilja E, Boodoo C, Luchini-Colbry K, Ruegg P, McLamore E, et al. Next generation of amr network. Encyclopedia. 2021; 1(3): 871–92.

17. Chowdhury AS, Lofgren ET, Moehring RW, Broschat SL. Identifying predictors of antimicrobial exposure in hospitalized patients using a machine learning approach. J Appl Microbiol. 2020; 128(3): 688–96.

18. Briliyanti A, Rojewski JW, Luchini-Colbry K, Colbry D. CyberAmbassadors: Results from pilot testing a new professional skills curriculum. In: Practice and Experience in Advanced Research Computing. 2020. p.379–85.

19. Velazquez-Meza ME, Galarde-López M, Carrillo-Quiróz B, Alpuche-Aranda CM. Antimicrobial resistance: One Health approach. Vet World. 2022; 15(3): 743–9. doi:10.14202/vetworld.2022.743-749

20. Wibisono FJ, Widiasih DA, Nguyen-Viet H. Multidrug Resistance of Escherichia coli in cats and the Level of Understanding of Cat Owners on Antimicrobial Resistance. Res J Pharm Technol. 2024; 17(8): 3855–8. doi:10.52711/0974-360X.2024.00598

21. Mahedi MRA, Mounich K, Hsu CY, Bhuiyan JR, Jasim IK, Khalaf OM, et al. Cefiderocol (CFDC): A Spy Antibiotic Future Replacement of Carbapenem. Res J Pharm Technol. 2023; 16(11): 5492–6. doi:10.52711/0974-360X.2023.00888

22. Choudhary MI, Römling U, Nadeem F, Bilal HM, Zafar M, Jahan H, et al. Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance. Microorganisms. 2023; 11(1): 16. doi:10.3390/microorganisms11010016

23. Katharios-Lanwermeyer S, O’Toole GA. Biofilm Maintenance as an Active Process: Evidence that Biofilms Work Hard to Stay Put. J Bacteriol. 2022; 204: e00587-21. doi:10.1128/jb.00587-21

24. Lundberg JO, Weitzberg E. Nitric oxide signaling in health and disease. Cell. 2022; 185: 2853–78.

25. Afrin S, Hasan MS, Mahedi MRA, Kuri OC, Iqbal H, Kadham MJ, et al. Eltrombopag Olamine in Dengue Fever: Systematic Review of Clinical Trials and Beyond. Res J Pharm Technol. 2024; 17(6): 2778–82. doi:10.52711/0974-360X.2024.00436

26. Wilson DN, Langer R, Anderson DG, Peppas NA, Park K, Moghimi SM, et al. Novel antimicrobial delivery systems. Adv Drug Deliv Rev. 2024;195:114568.

27. Kumar V, Blundell TL, Baker D, Schreiber SL, Wilson IA, Shoichet BK, et al. Novel drug targets through structural biology. J Med Chem. 2024; 67: 567–80.

28. WHO Expert Group. Future policy frameworks for AMR control. Bull World Health Organ. 2024; 102: 234–46.

29. Deepigaa M. Antibacterial Resistance of Bacteria in Biofilms. Res J Pharm Technol. 2017; 10(11): 4019–23. doi:10.5958/0974-360X.2017.00728.4

Received on 03.07.2025 Revised on 11.11.2025

Accepted on 14.01.2026 Published on 01.07.2026

Available online from July 04, 2026

Research J. Pharmacy and Technology. 2026;19(7):3393-3400.

DOI: 10.52711/0974-360X.2026.00482

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Replacement	Functions	Merits	Demerits
Herbal Medicine	Phytochemicals	Efflux inhibitory activity against Gram negative bacteria Biofilm inhibitors. Quorum sensing inhibitors	Lack of standardization
Vaccine	Easy to use Limit onset of disease	Promote Specific Immunological Protection Prevent Bacterial And Viral Infection	Limited cross-protection with some pathogens
Monoclonal Antibodies	Prophylactic action Pre-emptive approach	Long half-life Highly specific Do not disrupt normal flora	Limited stain efficacy
Probiotics	Prebiotic Symbiotic Competitive exclusion	Useful for commensals gut bacterial health Prevent pathogen colonization	Mixed efficacy of a single probiotic
Predatory Bacteria	Alter and consume other bacteria	Effective against biofilm Can access recalcitrance infection	No interaction between host and commensals
Phage Therapy	Narrow host spectrum Great diversity Bacteriolysis	Lytic activity independent of antibiotic resistance Do not infect eukaryotic cells Found naturally in environment	Potential ability to induce horizontal gene transfer by generalized transduction
Nano-particles	Low minimum inhibitory concentration (MIC) Unique physical and chemical properties	Can target multiple cellular pathways at once Can penetrate through cell wall and kill bacteria Used to treat multiple drug-resistant bacteria	High cost of drug development Toxicity
Bacterial cell wall hydrolases	Lysozymes Autolysins Virolysins	Highly effective against antibiotic resistant bacteria Safe and well understood Immunogenicity is not a concern for their effectiveness	Non-effective against many Gram-negative bacteria Some Gram-positive stains also resistant to lysozymes