The Role of Emerging Antibiotics in Addressing Antimicrobial Resistance: A Pharmacological Review

Antimicrobials is a term that consist of antibiotics, antifungals, antivirals and antiparasitic – are the drugs employed for preventing and curing different infectious ailments typically arise in humans, plants and animals.[1] Antimicrobial resistance (AMR) is recognized as one of the leading global health and development issues. Its rise is mainly driven by the overuse and improper use of antimicrobial agents in humans, animals, and plants. This misuse accelerates the emergence of pathogens that no longer respond to conventional treatment.[2] AMR represents a global health crisis that occurs when bacteria, viruses, fungi, or parasites no longer respond to antimicrobial therapies. These resistant infections are harder to treat and increase the likelihood of disease spread, severe health outcomes, and mortality. As a result, once-effective treatments become less reliable, allowing infections to persist and spread to others.[3] These resistant organisms are often referred to as "superbugs".[4]

Types of AMR:

Antimicrobial resistance is generally categorized into two main types: [33]

• Intrinsic Resistance
• Acquired Resistance

Intrinsic or natural resistance is the built-in ability of certain bacterial species to resist the effects of specific antibiotics.[33] This means the antibiotic is inherently ineffective against them due to natural characteristics of the bacteria.[34] The most common mechanisms by which bacteria exhibit intrinsic resistance include reduced permeability of their outer membrane and the presence of naturally occurring efflux pumps that expel antibiotics.[33]

Eg: one type of bacterium (bacteria, plural) may have a cell wall that can keep out some antibiotics. [34]

Acquired resistance arises when a bacterium that was originally sensitive to anantibiotic gains the ability to withstand its effects. Bacteria can acquire this resistance by taking up genetic material through transformation, transposition, or conjugation—collectively referred to as horizontal gene transfer (HGT). They may also develop resistance through spontaneous mutations in their chromosomal DNA. where a naturally susceptible microorganism acquires means of not being influenced by the drug.[33]

Impact of AMR on animal, humans, plants and environment:

The emergence of new drug-resistant bacterial strains in land and water animals often leads to increased suffering and economic loss. This ultimately affects global livelihoods, especially for the 1.3 billion people relying on livestock and over 20 million dependents on aquaculture. Proper antibiotic use and safe disposal of unused or expired medications, along with regulated industrial waste management, are crucial in minimizing environmental contamination and the spread of resistant microbes.[5]

Silent Pandemic and Agriculture

Overuse of antibiotics in human and veterinary medicine, as well as in agriculture, contributes significantly to the rise of resistance genes—fueling a so-called “silent pandemic” that could surpass current leading causes of death by 2050. [5][6]

Hospital Impact

Today, resistant strains are increasingly affecting hospitalized individuals worldwide. Infections like drug-resistant gonorrhea, urinary tract infections (cystitis), and those linked to common surgeries such as hip replacements are becoming harder to treat. [5]

Importance of Antimicrobial Resistance:

Threat to Modern Medicine: AMR compromises the effectiveness of antibiotics that are essential for treating infections and performing life-saving procedures. [9]

Global Health Security: AMR is a serious global health threat because resistant infections can spread rapidly across borders, affecting people of all ages and health statuses. [10]

Economic Impact: If left unchecked, AMR could costtheglobaleconomyupto$20trillion (about $62,000 per person in the US) by 2050 due to rising healthcare expenses and reduced productivity. [7][8]

Morbidity and Mortality Data

In 2019, antimicrobial resistance was directly responsible for approximately 1.27 million deaths and contributed to another 4.95 million deaths worldwide. If current trends continue, this figure is projected to reach 10 million deaths per year by 2050. [10]

Figure1: Projected death rate from AMR vs. most frequent cause of actual deaths [10]

Overview of individuals that are more susceptible to these AMR:

Newborns: 3 million annual sepsis in newborns, resulting in 570,000 deaths from drug resistance. Some antibiotics are currently only 50% effective in curing sepsis and meningitis in newborns.[12]

Older adults: Especially those in long- term care facilities, are particularly vulnerable to drug –resistant fungal infections like Candidaauris, which are associated with notably high mortality rates ranging from 30% to 60%.

Women: Drug-resistant urinary tract infections are a common and prevailing reason for global antibiotic prescribing.[12]

Low- resource environments: Limited healthcare infrastructure and systemic inequalities contribute to significantly elevated AMR-related mortality, such as the 27.3 deaths per 100,000 reported in western sub – Saharan African in 2019.

People with chronic conditions: Individuals with conditions like diabetes and cancer are at greater risk of developing drug- resistant infections.[12].

Figure2: Impact of Antimicrobial resistance on human health [20]

1. Prolonged illnesses: Antimicrobial resistance can result in extended periods of illness, heightening the chances of complications and negatively affecting overall quality of life.
2. Increased healthcare utilization: Patients with AMR infections often require more hospitalizations, surgeries, and intensive care unit (ICU) admissions, resulting in increased healthcare costs and resource utilization.
3. Chronic conditions: AMR may contribute to the development or worsening of long-term health conditions like chronic obstructive pulmonary disease (COPD) or cystic fibrosis, which can substantially influence both morbidity levels and the quality of daily living.
4. Contributing factors to AMR:

Excessive and inappropriate use of antimicrobial agents [16]

• • • Poor prescribing
    • Patient demand
    • Economic incentives
    • Lack of adherence to prescribed medicine
  • Poor quality medicines.[16]
  • Lack of knowledge by prescribers and users.[18]
  • Poor sanitation in clinics.[15]
  • Overused antibiotics in livestock farming and crop production.[13]
  • Natural evolution leading to genetic changes.[17]
  • Lack of new antibiotics being developed.[14]

Discontinuing treatment prematurely, such as stopping medication once symptoms improve rather than completing the full prescribed course.” [23]

Figure 3: Various causes of AMR [19] Mechanism action of AMR

Bacteria produce enzymes that breakdown antibiotics, for example:

β-lactamases that specifically target the β-lactam ring present in β-lactam antibiotics.” “Carbapenems, which are capable of degrading the entire β-lactam class of antibiotics.”

2. Enzyme Modification:[27]

“Bacteria can develop or acquire enzymes that either alter the antibiotic’s target site or modify the antibiotic molecule itself,” such as: - erm genes, which methylate the ribosome, making it resistant to macrolide antibiotics

2. • Aminoglycoside-modifying enzymes, which introduce an acetyl group to amino glycoside antibiotics, thereby reducing their efficacy.
3. Alteration of the antibiotic’s target site: [27][28]

Bacteria may alter the antibiotic’s target site through specific genetic mutations, such as:

3. • Mutations in penicillin binding proteins, which make Streptococcus pneumoniae resistant to penicillin
   • Genetic Mutations in DNA gyrase and DNA topoisomerase IV, can render bacterial pathogens resistant to fluoroquinolone antibiotics.
4. Replacement of the target site: [27]

Some bacteria acquire an extra copy of a gene encoding a protein that confers resistance to the antibiotic, as seen in examples like:

4. • Methicillin-resistant Staphylococcus aureus (MRSA), for instance, acquires an additional copy of penicillin binding protein 2a.
5. Over production of the Target: [27]

In some cases, bacteria increase the production of the antibiotic’s target, making it resistant to the antibiotic, such as: - Escherichia coli and Hemophilus influenzae, which overproduce the target of trimethoprim.

6. Efflux and Reduced Permeability:[27][29]

“Efflux and Reduced Permeability: Bacteria may either acquire extra efflux pumps or alter their membrane structure to lower the internal concentration of the antibiotic, contributing to resistance. Examples include:”

-TetA efflux pumps, which actively expel tetracycline from the bacterial cell.”

-“Loss or alteration of porin channels, which decreases membrane permeability and limits antibiotic entry.”

Figure 4: Mechanism of antimicrobial resistance [26]

• Discussion of genetic and molecular basis of AMR:

Genetic basis of AMR:

1. Chromosomal methods-Mutation:[30]
   • It is a heritable and stable alteration in the structure of the bacterial DNA
   • The spontaneous and random mutations occur in bacterial cells at an approximate rate of one per million.
   • “During antibiotic treatment, resistant bacteria can continue to grow and multiply, resulting in the selection of mutants that are resistant to the drug.”
   • Mutations can happen in bacterial DNA, and this results in alteration of the site of action of the antibiotic, e.g., the penicillin-binding protein (PBP) in streptococcus pneumoniae

Mutants due to chromosomal mutation possess lesser pathogenicity, apart from Mycobacteria species (causing tuberculosis and leprosy) and methicillin resistant staphylococcus aureuas (MRSA)

2. Plasmid–Based chromosomal Mechanism:[30]
   • Plasmids are additional chromosomal genetic components that serves as vectors for DNA transfer.
   • “Plasmids are small, self-replicating circular DNA molecules that carry antibiotic resistance

genes and can be exchanged between bacterial cells.”

• • “Plasmids harboring resistance genes are referred to as R-plasmids.”
  • Resistance genes can be readily transferred from one R-plasmid to another
  • Transfer of resistant genes can occur between bacteria cells of the same species or across

different species.

3. Gene amplification: Microbes may amplify genes of resistance, like ampC in Escherichia coli that carries the information to code a beta –lactamase enzyme. [31]
4. Gene transfer: Microbes can share genes for resistance from other microbes via horizontal transfer of genes by processes like conjugation, transformation, or transduction. [31]

Molecular basis of AMR:[32]

1. Enzyme-Mediated Resistance: Bacteria can produce enzymes that degrade antibiotics, e.g., beta-lactamases, which enzymatically break down beta-lactam antibiotics.
2. Target Modification: Bacteria can modify the target site of the antibiotic, e.g., the bacterial ribosome, making it less effective against the antibiotic.
3. Efflux Pumps: Bacteria may develop efflux systems that export antibiotics from the cell, diminishing their potency.
4. Cell Wall Adaptations: Bacteria adapt the cell wall to decrease the uptake of antibiotics, often by reducing the permeability of the outer membrane

Factors influencing antimicrobial resistance:[24][25]

• • Drug Associated factors
  • Environmental factors
  • Patient related factors
  • Prescriber related factors

Drug related factors:[25]

1. Falsified or Substandard drugs
2. Variability in drug quality
3. Widespread and indiscriminate use of antibiotics
4. Unregulated over- the – counter access to antimicrobial agents
5. Inappropriate use of fixed dose combination of antimicrobial agents
6. Substandard and counterfeit drug leading to sub-optimal blood Concentration
7. Growing overuse of antibiotics [24]

Environmental factors:

1. Massive populations and overcrowding [24][25]
2. Inadequate sanitation [24][25]
3. Emergence of community acquired resistance [24][25]
4. Faster spread as a result of improved transport facilities [24][25]
5. Extensive use of antibiotics in agriculture and live stock production, and as medicated hygiene products [25]
6. Poor infection control program [25]

Patient related factors:[24][25]

1. Non-compliance with prescribed dosage regimens
2. Limited financial resources.
3. Self-medication
4. Misconception
5. Lack of sanitation concept

Prescriber/physician related factors:

1. Inadequate dosing [24][25]
2. Insufficient up-to-date knowledge and clinical training [24][25]
3. Frequent empiric use of multiple antimicrobial agents [24][25]
4. Overuse of antimicrobials [25]

Global Epidemiology of AMR in Europe:

> 650,00 infections caused by antibiotic resistant bacteria resulting in:

> 30,000 attributable deaths[35]

> 870,000 disability-adjusted life years (DALYs) [35]

Figure 5:Usage of antibiotics in EU countries [35]

“Several key factors contribute to the definition and understanding of AMR across Europe:”

1. Resistance Prevalence: Various European nations have different rates of resistance among prevalent pathogens. For instance, methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli are commonly encountered across multiple regions. Southern and Eastern European nations tend to have higher rates of resistance than Northern and Western Europe.
2. Antibiotic use: The administration of antibiotics is a key contributory factor in AMR. Nations with more antibiotic use generally have greater rates of resistance. For instance, Southern European nations such as Italy and Greece have been reported to have high antibiotic prescribing rates that are associated with higher resistance.
3. Surveillance Systems: The European Centre for Disease Prevention and Control (ECDC) along with European Surveillance of Antimicrobial Consumption Network (ESAC-Net) play pivotal roles in tracking AMR trends and antibiotic consumption throughout Europe. They provide data that helps identify trends and guide public health interventions.

4. Infection Control Procedures: The level of effectiveness for infection control practice in healthcare organizations differs between nations. Countries that have robust infection prevention practices generally have fewer incidents of AMR. Poor infection control, however, can increase the occurrence of resistant infections by causing outbreaks.

5. Public Awareness and Education: “Responsible antibiotic use is essential in addressing this issue. Public awareness campaigns focused on antibiotic stewardship are therefore highly valuable.” “The challenges related to the misuse and overuse of antibiotics remain prevalent across numerous European nations.

6. Legislation and Policy: Various policies have been enacted in different countries to address AMR, ranging from policies on the prescription of antibiotics, enhancing antibiotics, on the development of new antibiotics, to developing prompt diagnostic tests to minimize antibiotic overuse.

• Prevalence of AMR in types of infections:[36]

AMR is a growing concern worldwide, compromising our capacity to treat infectious treat diseases and carry out life-saving surgery. The development and dissemination of resistant microorganisms are a result of the misuse and overuse of antibiotics persist across numerous European countries.

1. Infections caused by bacteria:

The current scenario regarding drug-resistance among bacteria is alarming, with:

- “Reported rates indicate 42% resistance in third-generation cephalosporin-resistant E.coli and 35%  in methicillin-resistant Staphylococcus aureus across 76 countries.”

- Approximately 1 in 5 urinary tract infections caused by E.coli exhibit reduced susceptibility to commonly used antibiotics.

- Significant levels of resistance against key antibiotics in Klebsiella pneumoniae [36]

2) Fungal Infections

The development and dissemination of multi-drug-resistant Candida auris is an emerging fungal pathogen, associated with life threatening infections. Fungal infections are hard to treat, and resistance to antifungal drugs is an increasing menace. [36]

3) HIV Infections: Drug-resistant HIV disease is a principal cause of public health concern with enhanced HIV illness and HIV/AIDS mortality. Antiretroviral drug use mismanagement and abuse have spawned the development of resistant HIV isolates. [36]

4) Tuberculosis (TB): “Multi drug-resistant tuberculosis (MDR-TB) remains a major contributor to the global AMR burden. In 2022, treatment was provided to only about two out of every five individuals with drug-resistant TB. These strains represent a substantial threat to global health security.”

5) Malaria: The development of drug-resistant malaria parasites presents a serious challenge to effective malaria control. The resistance to artemisinin-based combination therapies (ACTs) is of growing concern, necessitating robust surveillance efforts to monitor resistance trends. [36]

6) Neglected Tropical Diseases (NTDs): “Drug resistance in treatments for neglected tropical diseases poses a significant threat to efforts aimed at disease control, elimination, and eradication.”Resistance has already emerged in medications used to treat leprosy, helminthics, and human African trypanosomiasis and leishmaniasis. [36]

The medical and economic costs of resistance:[52][53][54]:

The health and economic cost of antimicrobial resistance (AMR) is a major international concern that impacts individuals and healthcare systems. Below is a comprehensive description of the two facets:

1. Health Burden of AMR

• Higher Mortality and Morbidity: AMR causes more challenging infections to treat, leading to longer hospitalization, increased medical expenses, and higher mortality rates. The World Health Organization (WHO) approximates that AMR results in about 700,000 deaths annually globally, and this figure could escalate further if nothing is done.

• Restricted Treatment Choices: When bacteria are becoming resistant to available antibiotics, there are fewer choices of treatment for infections. This can result in the use of more toxic or less effective drugs, which have extreme side effects.

• Surgical and Medical Intervention: Most surgical interventions, including cancer therapy, organ transplants, and operations, are dependent on successful antibiotics to avoid infection. AMR puts these interventions at risk, thus making them unsafe.

• Effects on Vulnerable Patients: AMR strikes with higher frequency in vulnerable patients, such as the elderly, infants, and patients with chronic disease, causing increased rates of morbidity and mortality among these populations.

2. Economic Costs of AMR

• Enhanced Healthcare Expenditures: It usually involves costlier medications for treating resistant infections, increased days of hospital stay, and added follow-up services. This entails higher healthcare expenses for both individuals and the health care system.

•Reduced Productivity: Individuals afflicted with AMR-related infections can suffer from extended illness, resulting in lost workdays and reduced productivity. This has a snowball effect on the economy, especially for industries dependent on a healthy workforce. -

•Burden on Healthcare Systems: The impact of AMR on healthcare systems can result in full hospitals, higher healthcare demands, and difficulties in managing resources optimally.

•Global Economic Impact: The World Bank estimates that AMR may cost the global economy as much as $100 trillion (approximately $310,000 per individual in the US) by 2050 if not addressed. This is inclusive of healthcare costs, lost productivity, and reduced economic output.

The medical and financial implications of antimicrobial resistance are profound and extensive. AMR is tackled by harmonized action among healthcare, policy, and public awareness to contain its effects and protect future therapy.

Significance of antibiotics in contemporary medicine:

Antibiotics: Antibiotics is a "chemical produced by a microorganism that kills or inhibits the growth of another microorganism". [37]

- "Antibiotic" is derived from antibiosis, i.e., "against me"[38]

- Antibiotics are also referred to as anti-bacterial.

Eg of widely used antibiotics are:

• Penicillin

• Cephalosporins

• Macrolides

• Tetracyclines [37]

Importance:

Antibiotics have transformed the practice of medicine, saved countless lives and made it possible to treat diseases that were once incurable. The discovery of penicillin in the 1940s by Alexander Fleming's signaled the start of the antibiotics have become a mainstay of contemporary medicine. [40]

Regulating antibiotic prescribing:

To fight antibiotic resistance, policy makers seek to control antibiotic prescribing and encourage the prudent use of these medications. Education and awareness regarding antibiotic-resistant bacteria and the harm caused by antibiotic misuse are critical in this worldwide battle against drug-resistant infections. [41]

How antibiotics work:[42]

Antibiotics cure bacterial infections by killing bacteria or inhibiting and halting its growth. They achieve this by:

 • targeting the wall or coating of surrounding bacteria

• inhibiting bacteria reproduction

• inhibiting protein synthesis in bacteria

Most antibiotics need to be taken for 7-14 days (approximately 2 weeks). In a few cases, shorter courses are as effective.

Present problems in the antibiotic development:

The challenges facing the development of antibiotics today are complex and concerning. Scientific Challenges are the challenge of finding new chemical structures that are safe for human use and have the ability to target resistant bacteria effectively.[43] Moreover, Gram negative bacteria possess a protective outer membrane, and thus it is difficult to design antibiotics that can pass through this layer [44]. Economic Challenges also contribute significantly. The heavy expense of introducing new antibiotics at an estimated $1.4 billion (roughly $4.3 per individual in the US) for each registered drug and the modest financial rewards because of low prices and volumes of sales makes it a costly venture [43][44]. This has resulted in insufficient investment in the research and development of antibiotics, causing a stagnant pipeline. Regulatory and Structural Challenges also compound the problem. The long and complex route to approval, taking 10-15 years, and the high rate of antibiotic candidates that fail, estimated at between 1.5% and 3.5%, deter investors and slow down the development of new antibiotics [44]. Finally, Global Health Challenges highlight the necessity of collaboration. Antibiotic resistance is a worldwide problem, and the absence of access to effective antibiotics in low resource environments continues to aggravate the issue.[45] There is a need for a new, public health needs-based approach to tackle these challenges so that effective, affordable, and accessible antibiotics can be developed.

Methods to mitigate/decrease the antibiotic resistance:

Figure 6: Strategies To Combat Antibiotic Resistance [46]

New antibiotics are under development to target the increasing threat of antibiotic resistance. Two new class antibiotics for gram-negative bacterial infections are in clinical development by Roche, one to treat carbapenem-resistant Acinetobacter baumannii (CRAB) and the other for carbapenem-resistant gram-negative infections [47].

Scientists are also seeking new methods, including:

- Fully synthetic platforms: Constructing new macrolide antibiotics using modular building blocks [48].

- Non-culturable bacteria: Searching for bacteria that are unable to be cultured in laboratory media as sources of new antibiotics [49].

- Bacteriophages: Screening viruses that infect bacteria as potential antibacterial compounds [49].

- OXF-077: An SOS response inhibitor molecule that can repress the emergence of quinolone antibiotic resistance. [47]

- Teixobactin: A potential antibiotic agent found in soil microbes that disrupts cell-wall construction of Gram-positive microbes such as MRSA. [49]

- Peptidomimetic antibiotics: Creating antibiotics that mimic peptides to act against certain bacterial proteins [48].

- Darobactin: A new antibiotic from a nematode symbiont, with potential against several ESKAPE pathogens [48].

Other efforts, such as the Global Antibiotic Research and Development Partnership (GARDP) and the REPAIR (Replenishing and Enabling the Pipeline for Anti-Infective Resistance) programmes, are also attempting to support late-stage antibiotic discovery and clinical trials[48].

Future directions and conclusions:

• Discussion of future directions for tackling AMR:

Antimicrobial resistance (AMR) needs to be addressed in a multi-faceted manner, and education plays an important part in awareness and encouraging appropriate use of antimicrobials.

Educational Strategies

- Educational programs on AMR can be integrated into school curricula at primary school levels to raise awareness and encourage behavior change [49].

- Extracurricular and interactive activities like plays, debates, and clubs of interest may engage students and help them acquire and retain knowledge [49]

- Education efforts based on community can empower the local communities to learn about AMR and what they can do to fight against it [49].

The Role of Education in AMR Awareness

• Education has the potential to improve prescriber performance and increase citizens' awareness, developing a culture of stewardship and prudent antimicrobial use [50]
• Sound educational interventions have the potential to fill knowledge gaps and associated practices regarding AMR, especially in low-resource settings [50].

• Development of new diagnostic tools and technologies:

Figure7: Summarizing chart of the methods and technologies analysed in the present review [51]

Improving the accuracy, speed, cost-effectiveness, and ease of use of new diagnostic tools for Antimicrobial Resistance (AMR) should be prioritized in the development of new diagnostic tools. From the image, diagnostic methods can be classified as Conventional Methods, Non- Conventional Methods, and Microfluidic Technologies.

The following are the major considerations for developing new diagnostic tools:

1. Improving Conventional Methods:

Traditional diagnostic approaches to AMR encompass phenotypic and molecular-based methods. Refinement of these techniques can make them more reliable and efficient.

1. Enhancing Phenotypic Techniques

• Manual Techniques:

-Optimize agar dilution, disk diffusion, and broth microdilution for enhanced accuracy.

-Invent automated readings to decrease human error in interpretation.

• Automated Platforms:

-Refine existing systems such as VITEK®2COMPACT, Sensititre™, and ARIS™2Xto enhance throughput.

-Incorporate AI-driven analysis to improve detection speed and result interpretation.

B. Advancements in Molecular-Based Methods

• PCR-Based Methods:

Develop rapid and portable PCR techniques for on-site AMR detection.

 • Isothermal Amplification Methods:

Innovate more sensitive is other malamplification approaches for faster results

• DNA Microarrays:

Improve specificity and multiplexing capabilities to detect multiple resistance genes in one test.

2. Innovation sin Non-Conventional Methods:

Non-traditional approaches emphasize next-generation sequencing (NGS) and innovative spectroscopy for AMR detection.

A. Genome Sequencing and Metagenomics

-Create accelerated whole-genome sequencing (WGS) for real-time monitoring of AMR

.-Enhance pyrosequencing and nanopore sequencing to make the technologies accessible and deployable in the field.

-Streamline bioinformatics software for short-and long-read sequencing to improve pathogen identification.

B. Spectrometry-Based Approaches:

• MALDI-TOF Mass Spectrometry:

Expand mass spectrometry uses for quick bacterial identification and AMR profiling.

•Fourier Transform Infrared (FTIR) Spectroscopy Create portable FTIR devices to identify bacterial resistance patterns

3. Integration of Microfluidic Technologies: Microfluidics offers a miniaturized, high- throughput platform for AMR diagnostics

A. Spectroscopy & Colorimetric Methods

-Create low-cost, portable spectroscopy-based AMR detection systems.

-Improve colorimetric assays for real-time and visible detection of resistant strains.

B. pH and QCM-Based Technologies

-Use pH-based sensors to identify changes in resistant bacteria's metabolism.

-Apply Quartz Crystal Microbalance (QCM) systems to enable very sensitive AMR detection.

C. Point-of-Care (POC) and Multiplexing Strategies

- Develop POC diagnostics for bedside AMR detection at speed.

- Develop multiplexing tools that can detect several resistance genes in one go.

- Design single-cellor single-molecule detection technologies for ultra-sensitive identification of AMR.

Conclusion

The future of AMR diagnosis is to harness automation, AI-based analytics, rapid sequencing, and microfluidic technologies to build highly efficient, cost-effective, and easy-to-use devices for global AMR surveillance and control. Role of Pharmacogenomics and Precision Medicine in Antimicrobial Resistance (AMR): [56][57]

1. Introduction:

Antimicrobial resistance (AMR) is a worldwide health hazard caused by the excessive use and abuse of antibiotics. The integration of pharmacogenomics and precision medicine provides a new strategy for addressing AMR via personalized therapy and enhanced antimicrobial stewardship.

2. Pharmacogenomics: Personalizing Antimicrobial Therapy:

Pharmacogenomics allows for the tailoring of antimicrobial therapy to genetic differences affecting drug response and metabolism. This lowers the risk of under-or over-dosing, reduces side effects, and prevents unnecessary exposure to antibiotics—critical drivers of resistance emergence.

3. Precision Medicine: Targeted Interventions

Precision medicine integrates genetic, clinical, and environmental information to inform the use of targeted antimicrobials. By pinpointing the most suitable treatment for every patient, it restricts the application of broad-spectrum antibiotics and deters the selection pressure that promotes resistant strains.

4. Implications for AMR Mitigation:

These strategies enhance the effectiveness of treatments, save on healthcare costs, and facilitate improved infection control. For AMR, they promote timely and effective treatment decisions as well as retain the effectiveness of available antimicrobials.

5. Future Directions:

Implementing rapid genomic diagnostic testing and resistance surveillance in real time within the clinic will play a crucial role in taking the potential of precision medicine beyond controlling AMR.

• Emerging Technologies for AMR: CRISPR-Based Antimicrobials:[55]

• What is CRISPR?

 CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene-editing system that enables specific DNA sequence modifications. It has been found to have potential in fighting antimicrobial resistance (AMR) by targeting and removing antibiotic-resistance genes.

How CRISPR Works?

Figure 8: CRISPR/CAS9 Systems allow scientists to make targeted changes to an organism’s DNA[61] CRISPR-Cas systems work in three main stages: adaptation, expression, and interference. They utilize RNA-guided nucleases to destroy specific DNA sequences, conferring immunity against subsequent infections.

Potential of CRISPR in Fending Off AMR:

CRISPR has shown promise in targeting and deleting antibiotic-resistance genes, rendering bacteria susceptible to antibiotics again. It provides a new strategy to curb and limit antibiotic resistance among pathogens.

Limitations and Challenges:

Although promising, CRISPR antimicrobials have challenges of off-targeting, delivery route, and potential side effects. More research must bed one to maximize the methods and optimize safety and efficacy.

Prospects for the Future:

Base editing and prime editing, two CRISPR technology advancements, provides a far and more predictable results. Future advancements will concentrate on enhancing delivery methods, decreasing off-target effects, and increasing specificity.

In summary:

Antimicrobials based on CRISPR have potential in the fight against AMR. Even though there are still obstacles to overcome, new research and developments in CRISPR technology have the potential to completely change how we treat antibiotic resistance and influence antimicrobial therapy in the future.

• New Technologies to Fight Antimicrobial Resistance (AMR): Drug Delivery Using Nanotechnology:[58]

Nanotechnology's targeted antimicrobial action provides creative ways to fight.

Role of Nanotechnology:

Nanomaterials can disrupt bacterial membranes and biofilms, generate reactive oxygen species, and overcome efflux pump – mediated resistance. Types of nanomaterials used include:

• Metalnanoparticles: Oxide nanoparticles of zinc, silver, and gold have antibacterial qualities.

• Therapeutic molecules can be delivered and encapsulated by liposomes and polymeric nanocarriers.

Figure 9: Common types of nano –drug carriers [62]