eChapters

Introduction
Antimicrobial resistance (AMR) has emerged as one of the most alarming public health challenges of the 21st century, threatening the effectiveness of life-saving drugs and the future of modern medicine. This crisis is not limited to healthcare settings; it spans communities, agriculture, and the environment, impacting every facet of society. India, with its large population, high burden of infectious diseases, unregulated access to antibiotics, and considerable pharmaceutical manufacturing industry, stands at the forefront of the global struggle against AMR. The rise of resistant microbes stems from a complex interplay of factors: overuse and misuse of antibiotics in humans and animals, poor infection prevention practices, lack of sanitation, and environmental contamination from antibiotic waste. As a result, common infections are becoming harder to treat, surgical procedures riskier, and healthcare costs are escalating, all leading to increased morbidity and mortality. Tackling AMR requires robust intersectoral collaboration—no single stakeholder can succeed alone. Non-governmental organizations (NGOs), industries, and Corporate Social Responsibility (CSR) initiatives form a critical triad in India’s fight against AMR. NGOs drive grassroots education, advocacy, surveillance, and policy change, often bridging gaps where governmental capacity is limited. The pharmaceutical and healthcare industries, responsible for antibiotic manufacturing, distribution, stewardship, and infection control, play a pivotal role in curbing environmental emissions, supporting responsible use, and promoting the discovery of new treatments. Meanwhile, CSR channels the resources and expertise of corporations towards sustainable, communityfacing projects that promote awareness, improve hygiene, foster stewardship, and drive systemic change.

Introduction
Animal sector is growing very fast particularly in India as people’s purchasing power is increasing day by day. With increase in income, people’s dietary habit is shifting towards more animal origin products. The use of antibiotics for animal food production is growing very fast and India is the 4th largest country in the world regarding consumption of antibiotics in veterinary and animal husbandry sector. There is urgent need of AMR mitigation strategies to reduce the effect on human and animal health. As per the World Bank AMR can affect the global GDP upto 3.8% by 2050. Most of the countries in the world are very cautious regarding antibiotic residues and rejecting the livestock products which lead to economic loss. Many world agencies/forum such as CodexAMR Guidelines, UN Political Declaration on AMR Guidelines, Global Leaders Group on AMR reiterated judicious use of antibiotics. All-India Network Project on AMR inLivestock and Fisherieswas started in India to reduce the effect of AMR by educational awareness, adoption at field level, surveillance system and diagnosis but it didn’t meet out the desired outcome. Capacity building programmes in the field of AMR by training, reform in curriculum, collaboration from different fields of professionals can mitigate the harmful effect of AMR. According to the Food and Agriculture Organization (FAO), education and training play pivotal roles in translating knowledge into practical implementation, warranting the inclusion of Antimicrobial Use and AMR as integral components in professional education, postgraduate training, and continuing education within the food and agricultural sectors Training Strategies It involve Antimicrobial Stewardship training for healthcare professionals, public awareness campaigns, farmer education, and veterinary training on responsible antimicrobial use. Other critical elements include fostering collaboration through professional networks, building surveillance capacity, utilizing AI-driven tools for better decision-making, and promoting hygiene and infection prevention to reduce infection incidence and the need for antibiotics.
Training for Healthcare Professionals
There is substantial evidence that both healthcare workers and members of the public have knowledge gaps about appropriate use of antibiotics and mechanisms of antibiotic resistance. Surveillance is a prerequisite to estimate the magnitude of the AMR burden and to establish any intervention strategies, such as antimicrobial stewardship. In order to launch successful intervention approaches through cooperative efforts from different stakeholders (e.g., international agencies, human and veterinary medicine sectors, agriculture and animal production industries, and consumers), the existing knowledge gap needs to be addressed first.

Introduction
Antimicrobial resistance (AMR) has emerged as one of the most pressing global health threats, with implications that extend beyond human medicine to animal health, food security, and the environment. In livestock production systems, the misuse and overuse of antibiotics contribute significantly to the development of resistant pathogens. These resistant organisms can spread from animals to humans through direct contact, contaminated food products, and environmental pathways. The containment of AMR in livestock is not solely a technical or regulatory challenge—it is also a social and behavioral issue. Public awareness, education, and behavioural change are key pillars of any effective AMR mitigation strategy. Schools, community networks, and media platforms play vital roles in shaping knowledge, attitudes, and practices related to antibiotic use in livestock.
Causes of AMR in Livestock
Over-prescription and misuse of antibiotics in veterinary care Use of antimicrobials as growth promoters rather than for therapeutic purposes Poor farm bio-security and hygiene leading to frequent infections
Inadequate regulation and over-the-counter sale of antibiotics without veterinary oversight
Public Health Impact
Transmission of resistant pathogens via the food chain Contamination of soil and water with resistant genes through manure
Emergence of zoonotic diseases with limited treatment options

Introduction
AMR is a critical global problem that affects human, environmental, and animal health. AMR is a complex problem; it is necessary to look at it from different disciplines to frame it within the One Health approach [Shrestha,2018].The World Health Organization (WHO) has identified AMR as a top ten global public health threat.Globally, there were an estimated 4.95 million deaths associated with bacterial AMR in 2019, including 1.27 million deaths attributable to bacterial AMR [O’Neill, J. (2016)]. The economic impact is equally alarming. The World Bank projects that AMR could lead to an additional US$ 1 trillion in healthcare costs by 2050, and over US$ 1 trillion in annual gross domestic product (GDP) losses by 2030.The One Health approach is defined as a joint effort of various disciplines that come together to provide solutions for human, animal, and environmental health. AMR is linked to each of these three components due to the irresponsible and excessive use of antimicrobials in various sectors (agriculture, cattle raising, and human medicine). Under the pressure of antimicrobial selection, bacteria acquire resistance genes and mobile genetic elements that can spread to other bacteria of the same or different genus. When bacteria acquire resistance to antimicrobials, they also acquire a greater ability to proliferate in animals, humans, and the natural world. Mismanagement of antimicrobials, inadequate infection control, agricultural debris, contaminants in the environment, and migration of people and animals infected with resistant bacteria facilitate the spread of resistance [Collignon,et.,al,2018]. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and ani mal health and the balance of the ecosystem. Several international organizations (The World Organisation for Animal Health [OIE], WHO, and the Food and Agriculture Organization of the United Nations [FAO]) have joined forces to develop a Global Action Plan on Antimicrobial Resistance-WHO. Action taken in this plan included understanding the AMR from surveillance and research. The advisory group established guidelines for AMR surveillance to ensure all countries implement integrated surveillance, which will cover the use and consumption of antimicrobials in the human and animal population. These guide lines will provide a clear understanding of how AMR spreads in different settings and specific areas. It will allow to study the correlation between AMR and antimicrobial use in a different setting (animals, humans, and environment) and to assess the effect of interventions within and between sectors [W.H.O 2015,2017].

Introduction
Antimicrobial resistance (AMR) is increasingly recognised as a “silent pandemic,” threatening global health and development. In 2019 alone, bacterial AMR was directly responsible for 1.27 million deaths and contributed to nearly 5 million more worldwide. Projections warn that by 2050, unchecked AMR could result in 10 million annual deaths and impose a staggering economic burden of USD 100 trillion. A major driver of this crisis is the indiscriminate and often prophylactic use of antibiotics in livestock production systems, which account for a majority of global antimicrobial consumption. The One Health framework—emphasising the interconnectedness of animal, human, and environmental health—offers a strategic pathway for mitigating AMR. It requires dismantling sectoral silos and fostering collaboration among veterinarians, physicians, public health authorities, food safety regulators, and environmental scientists. Against this backdrop, NDDB has positioned itself as a frontrunner in India by embedding One Health principles into large-scale field programmes. Since 2014, NDDB has progressively promoted alternative medicine for bovine mastitis control under its Mastitis Conrol Project (MCP), subsequently expanding in 2017–18 into a broader Disease Control through Alternate Methods (DCAM) project with Ethnoveterinary Medicine (EVM) as the central pillar.
Building Up: From DCAM to DISHA as One Health Strategy
Building on the successes of MCP, DCAM, and BCP, NDDB launched the Dairy Integrated Safety and Health Action (DISHA) project for 2025–2030, DISHA consolidates NDDB’s One Health strategy by combining animal health management, zoonotic disease surveillance, and food safety monitoring. Its objectives include: managing bovine cases with EVM, organising farmer awareness programmes, training veterinarians and health workers, screening cattle as well as their owner for brucellosis, and testing bulk milk samples for aflatoxins and antibiotic residues. Importantly, DISHA also addresses emerging food system contaminants such as microplastics, per- and polyfluoroalkyl substances (PFAs), Bisphenol-A (BPA) and heavy metals, thereby broadening the scope of One Health beyond infectious diseases.

Introduction
It is reasonable to consider that the history of humanity has been marked by two transformational revolutions: the cognitive revolution (35,000 to 70,000 years ago), when Homo sapiens began to manifest our capacity to abstract, imagine things that did not exist and give meaning to non-representational thoughts; the agricultural revolution (10,000 to 12,000 years ago), when Homo sapiens stopped being a hunter/collector to settle on land, cultivating the soil and raising domesticated animals. It was possibly the beginning of property ownership, monogamy, family and also when malaria, and other diseases more easily spread in communities, became consolidated as human diseases. It was with the cognitive revolution that things changed and our previously acquired abilities of creating images and dealing with abstract concepts started to push humankind to become the “Dominant Mammal” controlling all other animals and Earth’s environments. Progressively, man learned to work with wood, iron and all minerals extracted from the soil, produced clothes with leather and wool from animals, linen and cotton from plants, silk from insects, and latter from natural oils created arts, jewellery, dynamite, electricity, vaccines, transatlantic ships, locomotives, cars, computers, antibiotics, contraceptives, robots, portable cell phones, informatics, bioengineering, internet, artificial intelligence, social networks and many other innovations . Not surprisingly, conscious of all these attributes, man felt important, central and essential, falling into the temptation of judging himself a magnificent creature with all rights and that became deep rooted in some cultures. For the pleasure,comfort, sophistication and power, man interfered with and altered the environment in a so ambitious and predatory manner that he modified and compromised his and other species living conditions, causing also climate changes that threaten his own survival on the planet. With time, it became clear that, in addition to this entirely anthropocentric “Ego’s” point of view, there might be another perspective fromwhich one can perceive the world and interact with it. An ecological “Eco’s” perspective corresponds to a compassionate view (how can we contribute to the greater good and make the world a better place) of the Globe. After all the damage done to nature by man, moving from the socalled Ego to the Eco attitude became a mandatory needConcerning Global Health, for a long-time, human health has benefited by sacrificing the “health” of wild ecosystems (e.g., deforestation and conversion of wilderness to farmland, damming of water for irrigation, destruction of swamps and dislocation and jeopardy of wild species) which reflects a protectionist vs utilitarian conflict, over the question of whether to put human domination of the biosphere on hold or whether to embrace it .It hides unaddressed concerns about the value of (macroscopic) life (human, animal or plant), the definitions of health and wellbeing (human, animal, plant and environmental) and their relative importance. This has hampered the development and acceptance of a One Health (OH) understanding of Global Health.

Our animal companions are our family members. We want the best for them and want them to be healthy and happy. However, just as it is with everyone else, our companion animals can also fall ill and suffer from emotions such as grief, fear, and anxiety. And while we follow all expert medical advice, sometimes we may wish for something more – something that will make life easier for them as well as us. This is where the concept of energy healing for animals comes in – to comfort and support our animal companions. With joy, we watch them relax with a sigh; we see our nervous dogs calm down, and those recovering from an acute illness get back on their paws in no time. Energy healing for animals involves a holistic approach to ensure the physical, emotional, and spiritual well-being of our animal friends. It is based on the fundamental concept that just like us, our animal companions too have a subtle energy layer, and they too have vital life-force energies or Prana or Qi. And just like us, they, too, have chakras and meridians through which the Qi flows. Energy healing is a set of powerful techniques practiced to calm and restore the balance of the body. This system is largely based on the removal of energetic blocks and helps restore the body’s energy levels. It is crucial for those living with companion animals to understand the importance of energy healing for their animal companions, as it encompasses a broad range of alternative and complementary therapies designed to support the natural healing process of animals. Here are some proven, popular, non-invasive energy healing techniques that bring relief and comfort to companion animals.
1. Animal Reiki: The word Reiki means “mystical energy.” The system of Reiki for healing was revealed by Japanese Buddhist practitioner Mikao Usui in the early 1900s. And while it was initially meant for humans, practitioners soon discovered that animals responded much more swiftly and effectively to this gentle, non-invasive energy work.
2. EFT Tapping: This involves tapping on specific points on the body to free up emotional blocks. EFT Tapping for animals brings powerful transformations when an animal is struggling with emotional distress, such as grief over the loss of a loved human or animal.
3. Scalar Wave Healing: Scalar Wave was discovered in the 1900s by James Maxwell and later Nicolas Tesla. Scalar Wave harnesses the healing power of high vibrational frequencies meeting to create a standing wave, and practitioners use this to bring about healing at a cellular level.
4. Shamanic Healing: In this ancient technique, practitioners work with the elements of nature, such as plants, trees, and stones, as well as beings in other dimensions, to bring about healing. Shamanic healing can reach beyond space and time and has been very effective in releasing old trauma or emotions that are often hidden beneath layers of survival mechanisms.
5. Healing Mantra: Ayurveda, the Indian system of medicine, advocates about different types of Chikitsa. Daivavyapashraya Chikitsa is one of the treatment approaches concerned with Spiritual way of treatment. It includes so many approaches, amongst all Mantra Chikitsa is described in Ayurveda at various places as a potent approach. It is discussed for both the healthy and unhealthy conditions. Mantra comes from Sanskrit word which means sacred message or text, spell. The word Mantra is derived from Man+Tra, man—mananaat---just by chanting and tra—trayate---- we can protect ourselves. Means, just by chanting one can save himself in the universe. i.e. it is saved from onset of disturbances. Mantras are the words loaded with power and sounds capable of penetrating our body into deep levels. Mantra chikitsa is the ancient science originated from Vedas, this is a parallel science to Ayurveda also called alternative medicine system.Mantra Chikitsa is one among the Daivavyapashraya Chikitsa highlights the importance of concept of Mantra. In Atharva Veda and Kaushikasutra, the two most ancient and authentic sources of Daivavyapashraya. Mantra Chikitsa is mainly used for both preventive and curative aspect. It is also used for the enhancement of the Gunas of Aushadhi. Effect of Mantra is described as Prabhavajanya action. Prabhava means the specific and characteristic action of substances, it is called as Acintya. Mantra Chikitsa cure the Karmaja Vyadhi and Agantuja Vyadhi. In the Vedic period, Daivavyapashraya Chikitsa was followed in various rituals.

Introduction
The safety of meat and its derivatives is a paramount concern in the dynamic realm of food trade. Consumers demand food products that are not only affordable and possess an extended shelf life but are also of high safety standards. Consequently, meat inspections require strict adherence to good manufacturing practices and safety labelling that aligns with regulatory standards. Food-borne pathogens, including Listeria monocytogenes, Staphylococcus aureus, pathogenic Escherichia coli, Clostridium perfringens, Campylobacter spp., and Vibrio spp., are responsible for numerous illnesses, thereby exerting a significant impact on public health and the economy. According to the World Health Organization (WHO), food contaminated with pathogens, chemicals, and allergens results in 600 million cases of food-borne illnesses and approximately 400,000 deaths globally each year. Furthermore, 56 million individuals die annually, with about 7.7% of the global population affected by foodborne diseases. Meat and meat products are essential sources of nutrients for humans, providing high-quality protein, essential amino acids, B vitamins, and minerals. However, due to their high-water activity and nutrient content, they also create a conducive environment for spoilage microorganisms and food-borne pathogens. Until a few decades ago, the meat industry was largely dominated by the unorganized sector, with limited access to knowledge that could enhance productivity. However, in the post-World Trade Organization (WTO) era, meat entrepreneurs have succeeded in increasing productivity, although they have faced challenges in ensuring product quality that aligns with the legislative standards of numerous developed and developing countries. The use of antibiotics as antimicrobial growth promoters in animal food production has been a contentious issue, as their unauthorized application has inadvertently contributed to the emergence of antibiotic-resistant bacteria within the food chain. Recently, the United States Trade Representative’s office estimated that international trade has expanded significantly since the General Agreement on Tariffs and Trade (GATT) was signed in 1947. The establishment of the WTO in 1995 further facilitated trade in animal-origin foods and live animals between nations. However, the emergence and re-emergence of diseases caused by pathogenic bacteria have become a significant concern in this new pattern of food trade. Some of these pathogens are so virulent that they were not previously reported. According to a 1998 report by the Centers for Disease Control and Prevention (CDC), the annual cost of foodborne illnesses in the United States is nearly 10 billion US dollars. The bacterial pathogens most commonly associated with illnesses from beef products include Salmonella spp., Clostridium perfringens, and Staphylococcus aureus. Interest in Escherichia coli O157: H7 increased following a highly publicized food poisoning outbreak linked to undercooked beef patties in the United States in 1993, although it was largely confined to North America until the mid-1990s. Similarly, multidrug-resistant Salmonella typhimurium DT-104 has spread widely since it was first identified in the United Kingdom. In India, the incidence of Salmonella in red meat was recorded at up to 9%. These potentially harmful bacterial pathogens can reside on the hides or in the intestinal tracts of foodproducing animals or may originate indirectly through cross-contamination or the processing environment. Other emerging foodborne diseases include Listeriosis, which has spread throughout France and Canada, where meat and meat products have been implicated as sources of Listeria monocytogenes. Similarly, Staphylococcal food poisoning or food intoxication syndrome, first reported in 1894, has become a global issue in the meat industry.

Introduction
Antimicrobial resistance (AMR) has emerged as a critical global health threat, diminishing the effectiveness of antibiotics against bacterial infections. Conventional strategies to counter AMR—including antibiotic stewardship programs and the development of new drugs—are often slow, expensive, and labor intensive. However, artificial intelligence (AI) and machine learning (ML) present ground breaking alternatives to address this challenge. By leveraging advanced computational techniques, AI can significantly speed up the discovery of novel antibiotics, enabling researchers to identify promising drug candidates more efficiently than traditional methods. Additionally, ML algorithms enhance treatment optimization by analyzing patient data to recommend personalized antibiotic regimens, reducing misuse and resistance risks. AI also strengthens surveillance systems by processing vast datasets— such as genomic sequences and electronic health records—to detect emerging resistance patterns in real time. These capabilities allow for proactive interventions, helping healthcare providers and policymakers stay ahead of AMR outbreaks. Together, AI and ML offer a transformative approach to mitigating AMR, combining speed, precision, and scalability to combat one of the most pressing medical challenges of our time.
AI in Antibiotic Discovery
One of the most promising applications of AI in AMR mitigation is in antibiotic discovery. Traditional drug development is costly and time-consuming, often taking over a decade [1]. Machine learning models can analyse vast datasets of chemical compounds to predict their antibacterial properties. For example, researchers at MIT used deep learning to identify halicin, a novel antibiotic effective against drug-resistant bacteria. AI-driven platforms can also repurpose existing drugs, reducing the time needed for clinical trials [2].
Fig. 1: AI cyclic interface in antibiotic discovery
Predictive Analytics for Resistance Patterns AI-powered predictive analytics enables early detection of antimicrobial resistance (AMR) patterns by processing clinical, genomic, and epidemiological data. Machine learning models analyse electronic health records (EHRs) [3] and bacterial genome sequences to identify emerging resistance threats in real time. These predictive insights allow hospitals to take proactive measures— such as optimizing antibiotic prescriptions—before resistant strains spread. Beyond clinical settings [4], AI models assist public health agencies in forecasting outbreaks and strategically deploying resources. By integrating large-scale datasets, these systems enhance surveillance, enabling faster, datadriven decisions to curb AMR progression. This approach not only improves patient outcomes but also supports global efforts in combating antibiotic resistance through smarter, pre-emptive interventions [5].

Introduction
Antimicrobial resistance (AMR) constitutes a profound global health crisis, jeopardizing the efficacy of antibiotics and posing a severe threat to the foundation of modern medical practice. The rise of multidrug-resistant (MDR) pathogens, which exhibit resistance to multiple classes of antibiotics, has significantly escalated the global burden of infectious diseases, complicating treatment protocols and increasing morbidity and mortality rates. According to the World Health Organization (WHO), AMR could lead to 10 million deaths annually by 2050 if current trends continue, accompanied by economic losses projected to reach trillions of dollars due to prolonged hospitalizations, increased healthcare costs, and reduced productivity. The traditional antibiotic development pipeline has stagnated, hampered by scientific complexities, high financial costs, and stringent regulatory frameworks, resulting in a critical shortage of novel antimicrobial agents. This necessitates the exploration of innovative strategies to combat AMR and preserve the utility of existing antibiotics. Among these strategies, Crispr-Cas (Clustered Regularly Interspaced Short Palindromic Repeats and Crispr-associated proteins) systems have emerged as a groundbreaking gene-editing platform with transformative potential for addressing AMR. Initially identified as a bacterial adaptive immune mechanism, Crispr-Cas has been repurposed to enable precise targeting of genetic elements, offering novel therapeutic, diagnostic, and environmental solutions. This chapter provides a comprehensive analysis of Crispr-Cas systems in the context of AMR, exploring their molecular mechanisms, diverse applications, current limitations, and future prospects across clinical, agricultural, and environmental domains. By leveraging the precision and programmability of Crispr-Cas, researchers aim to develop targeted interventions that mitigate the spread of resistance while minimizing collateral damage to beneficial microbial communities.

Introduction
Antimicrobial resistance (AMR) is an escalating global concern, rendering many once-effective antimicrobials useless and threatening modern medicine’s foundations [1]. RNA-based therapies offer precision, programmability, and modularity—tailoring interventions directly to microbial genetic machinery [2, 3].
Main RNA-based modalities include
• Antisense Oligonucleotides (ASOs): Short synthetic single-stranded RNAs that bind complementary mRNA in bacteria to inhibit translation or induce RNase H–mediated degradation [15].
• RNA Interference (RNAi): Though classically applied to eukaryotes, siRNAs or crRNAs delivered via nanoparticles (also termed “nanoantibiotics”) can silence microbial resistance or virulence genes while the carrier materials physically damage microbial membranes— enhancing lethality [3, 4,5].
• CRISPR-Cas Systems: Adapted as antimicrobials, CRISPR-Cas tools can precisely target and cleave resistance genes in pathogens via conjugative plasmids or phages [6].
• Ribozymes / External Guide Sequences (EGSs): Engineered noncoding RNAs that harness RNase P or ribozyme activity to degrade specific bacterial mRNAs [16].
Key strengths
• Target specificity—can silence essential microbial or resistance genes while sparing beneficial microbiota.
• Rapid design and adaptability—once delivery systems are in place, targeting new genes requires sequence change alone.
• Synergy potential—combining gene silencing with antibiotics or physical antimicrobial actions increases efficacy.

Introduction
A microorganism or microbe is a tiny living thing that can exist as a single cell or in groups of cells. People have suspected the existence of these unseen microbes since ancient times. These single-celled creatures have caused serious infections that often led to deaths and illness. These microorganisms can spread quickly and cause big outbreaks of disease. In 1928, Alexander Fleming discovered the first antibiotic, penicillin. This discovery started the development of one of the most important groups of medicines in medical history. In the next three decades, many different types of antimicrobial drugs were developed. In his Nobel Prize speech, Fleming warned that using penicillin too much might one day lead to bacteria becoming resistant to it, which would be a major problem. Antimicrobial resistance (AMR) is one of the biggest public health challenges today. Many of the microbes that cause diseases, like bacteria, viruses, and protozoa, no longer respond to common antimicrobial drugs such as antibiotics, antivirals, and antiprotozoals. Antimicrobial resistance is when a microbe becomes able to survive and grow even when treated with medications that used to work on it. Antibiotic resistance is a type of AMR, but it only applies to bacteria becoming resistant to antibiotics. Resistant microbes are harder to treat, and doctors may need to use other medicines or higher doses. These options can be more expensive and have more side effects. Microbes that resist multiple antimicrobials are called multidrug resistant (MDR). Those that are resistant to almost all drugs are sometimes called ‘superbugs’. Antimicrobial prophylaxis is used by doctors to prevent infections, but it should only be used when it’s really needed to avoid unnecessary costs, side effects, and the development of resistance. Antimicrobial prophylaxis can be used to prevent a first infection or to stop an infection from coming back or reactivating.

Introduction
The discovery of antibiotics and their subsequent use in combating infectious diseaseswas amedical breakthroughin the 20th century, as it completely changed the treatment approach to infections in general and bacterial infections in particular. In 1928, Alexander Fleming discovered Penicillin that started the started the so-called “golden age of antibiotic”. However, later in course of time the underuse, overuse and misuse of antibiotics in medical and veterinary practice led toemergence of drug-resistant pathogens resulting in phenomenon called antimicrobial resistance (AMR). In last few decades AMR has evolved silently and now threatening the human and animal health and has acquired the potential to be a next pandemic. AMR develops in a microorganism (e.g., bacteria, viruses, fungi, parasites) when it accumulates genetic changes over time and fails to respond to antibiotic(s) leading to severe illness and mortality due to infection. Although, AMR is an evolutionary event occurring naturally in microbes, but inappropriate use of antibiotics in humans and animal medicine act as key driver to its spread. Global antibiotic consumption increased between 2016 and 2023, with total consumption rising by 16.3% to 34.3 billion defined daily doses (DDDs) in reporting countries and a projected 20.9% increase when extrapolated to nonreporting countries. World Health Organization (WHO) and other authorities have called for coordinated action to address antimicrobial resistance, a threat looming large on horizon. In 2021, there were an estimated 1.14 million deaths attributed directly to Antimicrobial Resistance (AMR), with globally another 4.71 million deaths associated with AMR infections. This dataindicates a significant global health burden, with prophecy that AMR deaths could increase dangerously by 2050 if current trends continue. Global Action Plan (GAP) of the WHO highlights the importance of “One Health approach” calling for the joint action in human health, food production, animals and environmental sectors, to achieve better results. In the year 2015, the WHO initiated the Global Antimicrobial Resistance and Use Surveillance System (GLASS)to collect, analyze and share AMR data received from all countries. The Global Action Plan on AMR lists five strategic objectives to contain AMR viz., 1. optimizing the use of antimicrobials, 2. preventing infections (including the use of vaccines), 3. strengthening surveillance and research, 4. improving awareness and understanding of AMR, and 5. investing in new medical products. Vaccines stimulate the body’s immune system to recognize and attack specific pathogens and thus can prevent AMR through several ways viz., 1. reduce the incidence of infections leading to reduction in morbidity and mortality, 2. vaccines can prevent secondary bacterial infections e.g. Streptococcus pneumoniae after an initial infection with influenza, 3. produce herd immunity, 4. Prevention of infections resulting in decrease in use of antibiotics that reduces development of AMR. Immunotherapeutics can both combat and be complicated by Antimicrobial Resistance (AMR). Other immunotherapies antibodies, and immune-boosting agents can directly fight AMR by preventing infections and reducing the need for antibiotics.

Introduction
India with a population of 1.30 billion people is highly focusing on “Development”i.e. good food, better health & living conditions for everyone. With the increase in the incomes, people can now afford better nutrition in the form of poultry egg and meat, now poultry industry has transformed from a mere backyard activity into a major commercial activity in just four decades. India is now the world’s 3rd largest egg producer and the 5thlargest producer of broilers. The Indian poultry market witnessed an increasing trend over the past five years, growing at a Compound Annual Growth Rate (CAGR) of 8.6% (DAHD, 2023). Poultry sector in India is valued at about Rs. 1,50,000 crore (2022-23) broadly divided into two sub-sectors – one with a highly organized commercial sector with about 80% of the total market share (say, Rs. 1,20,000 crore) and the other being unorganized with about 20% of the total market share of Rs. 30,000 Crore. (DAHD, 2023). Poultry production in India has become a profitable and most popular income generating sector for the educated unemployed youth. Most of the poultry farmers are interested in broiler production due to its quick returns, less space requirement and higher weight gains. The productive potential of poultry in India has not been fully exploited due to deficit feed resources and unutilization of available improved technologies for getting high productivity from the poultry at economical rate. Hence, it is essential to further enhance the feeding value of available feed resources so as to improve the efficiency of feed utilization and minimize the cost of feed per kilogram live weight gain. The use of antibioticas growth promoters in poultry has been banned due to concern about their residues in tissue and induction of bacterial resistance. Due to these concerns, recently many feed additives has been investigated for alternatives tofeed antibiotics. The international feed industry is facing the challenge of the awareness among the consumers of meat on the risk of bringing about antibiotic resistance in pathogenic microbiota through antibiotics used in animal and poultry feeds. It has directed them towards the non-antibiotic feed additives. Among them, the feed additives of plant origin, called as Phyto-additives or Phytogenic Feed Additives (PFA) or Phytobiotics are considered to be a better alternative as non-antibiotic growth promoters, even though there are well established non antibiotic growth promoters such as organic acids and probiotics. The Phytogenic feed additives also vary widely in their botanical origin, processing and composition. They have been used in solid, dried and ground forms or as extracts or essential oils.It is reported that aromatic plants may increase feed intake and may improve secretion of endogenous digestive enzymes. It has been shown thatthe dietary incorporation of herbs may provide beneficial effect on poultry performance and health due to the antimicrobial activity of their phytochemical components. Phytobiotics have gained increasing interest as natural growth promoting feed additives in broiler production in recent years. These have wide range of medicinal properties with no residual side effects and are best alternatives to antibiotic growth promoters (Chaudhary et al., 2018, 2019, Rahman et al., 2014). Beneficial effects of these substances in poultry nutrition are due to their high content of pharmacologically active compounds stimulating appetite and feed intake, improving endogenous digestive secretion and activating immune responses (Nouzarian et al., 2011 and Toghyani et al., 2010).

Introduction
Antimicrobial resistance (AMR) is rapidly becoming one of the most critical challenges in global health, with profound implications for both human and veterinary medicine. The increasing prevalence of drug-resistant bacterial infections has eroded the effectiveness of many frontline antibiotics, making even routine treatments more complex and less predictable. Surveillance data from the World Health Organization’s GLASS initiative highlights the scale of the problem: resistance to third-generation cephalosporins in Escherichia coli and methicillin in Staphylococcus aureus has reached alarming levels in dozens of countries, complicating the management of common infections and raising the stakes for therapeutic innovation. In veterinary settings, the crisis is equally urgent. Resistance has emerged across nearly all major antibiotic classes used in livestock, poultry, and companion animals. Contributing factors include widespread antibiotic use in agriculture, limited diagnostic stewardship, and the ease with which resistance genes spread within and between microbial communities. These trends not only threaten animal health and productivity but also increase the risk of zoonotic transmission, blurring the boundaries between veterinary and human public health. Global health authorities have long warned of a “post-antibiotic era” - a time when conventional antibiotics may no longer offer reliable protection against bacterial pathogens. Recent reports suggest that this era is no longer hypothetical. If current trajectories continue, drug-resistant infections could account for up to 10 million deaths annually by 2050, with staggering economic consequences. To address this escalating threat, researchers are exploring alternative therapeutic strategies that go beyond traditional antibiotics. Among the most promising are antimicrobial peptides (AMPs) and bacteriophage therapy. AMPs are naturally occurring molecules found in animals and other organisms, known for their broad-spectrum activity and rapid bactericidal effects. Their ability to disrupt bacterial membranes through electrostatic and hydrophobic interactions makes them less susceptible to resistance mechanisms that target conventional antibiotics. Bacteriophages - viruses that specifically infect and lyse bacteria - offer a complementary approach. Phage therapy is highly targeted, capable of eliminating specific bacterial strains while sparing beneficial microbiota. Phage’s can also evolve alongside bacterial populations, potentially outpacing resistance development. In veterinary medicine, phage-based treatments have shown promise in managing infections in poultry, swine, cattle, and companion animals, particularly where antibiotic options are limited or ineffective. The combined use of AMPs and bacteriophages represents a novel and potentially synergistic strategy for tackling AMR. By leveraging distinct mechanisms of action and delivery profiles, these agents may enhance therapeutic efficacy, reduce resistance selection pressure, and improve outcomes across a range of veterinary applications. This chapter explores the pharmacological and pharmacokinetic challenges associated with delivering such combination therapies, with a focus on optimizing their use in the fight against antimicrobial resistance.

Introduction Antimicrobial resistance (AMR) has emerged as one of the gravest threats to modern medicine, undermining decades of progress in infectious disease control. It is cited by the World Health Organization (WHO) as one of the top 10 threats to global health. In 2019 alone, AMR was associated with approximately 4.95 million deaths, including 1.27 million directly attributable to resistant bacterial infections. This makes AMR a leading cause of death worldwide, surpassing HIV/AIDS (0.86 million deaths) and malaria (0.64 million deaths) in the same year. Projections suggest that if the trend continues unchecked, AMR could cause 10 million deaths annually by 2050, representing a profound human-cost escalation. Livestock and Animal burden While the quantitative burden of AMR in animals is not yet globally mapped, its effects in livestock are already both profound and alarming. Over 70% of all antimicrobials globally are used in farm animalsfrequently for growth promotion and disease prevention—not just treatment. This widespread use contributes to emerging resistance in key pathogens—Salmonella, E. coli, Campylobacter in poultry, and severe swine dysentery in pigs. In some outbreaks, swine dysentery, resistant to conventional treatment, has caused up to 90% morbidity and 30% mortality in weaned pigs. Animal-to-Human Transmission and the One Health Paradigm Antimicrobial resistance in livestock doesn’t stay on the farm—it seeps into the environment and crosses over to humans via food chains, direct contact, and environmental pathways. For example, substandard veterinary medicines and antibiotic misuse has been traced in zoonotic infections and veterinary-tohuman AMR transmission.Surveillance gaps remain: the World Organisation for Animal Health (WOAH) acknowledges that while human-related AMR mortality is well-documented, the animal health burden is not yet quantified globally—though numerous projects are underway to address this gap. The failure of conventional antibiotics to treat resistant infections highlights the urgent need for alternative therapeutic strategies. Among the most promising options is bacteriophage therapy—the use of viruses that specifically target and kill bacteria. Bacteriophages Bacteriophages, often referred to simply as phages, are viruses that infect and replicate within the bacteria. They are considered as the most abundant biological entities on Earth, with an estimated amount 10³¹ phage particles present in the biosphere—outnumbering bacteria by approximately tenfold. Phages are naturally found in diverse ecosystems including soil, ocean, sewage, and even within the microbiomes of humans and animals.

Introduction
Antimicrobial resistance (AMR) is a critical public health problem globally, which can shake the foundation of modern healthcare. Infections caused by drugresistant organisms could lead to increased mortality and prolonged duration of hospitalization, causing a huge financial burden to the affected persons, healthcare systems and hinder the goals of sustainable development. With rising AMR, antibiotics are increasingly becoming ineffective for treating diseases.The post antibiotic era is not a dreadful imagination but a potential reality unless effective global actions are initiated now (1). AMR is not the only problem of human health, it widely affects the animal husbandry as well as environment. In India in 2019, there were 297,000 deaths attributable to AMR and 1,042,500 deaths associated with AMR. India has the 145th highest age-standardized mortality rate per 100,000 population associated with AMR across 204 countries.The number of AMR deaths in India is higher than deaths from neoplasms, respiratory infections and tuberculosis, enteric infections, diabetes and kidney diseases and maternal and neonatal disorders.Out of 10 million projected human deaths in 2050, one-fifth may be from India (2).Annually, more than 50 000 new-born are estimated to die from sepsis due to pathogens resistant to first-line antibiotics. The median cost of treatment of a resistant bacterial infection in India is estimated to be more than a year’s wages of a rural worker. There are five pathogens to be aware of in India (number of deaths associated with AMR in parenthesis): Escherichia coli (152,700), Klebsiella pneumoniae (123,200), Staphylococcus aureus (111,400), Acinetobacter baumannii (103,500), and Mycobacterium tuberculosis (98,600).If there is no timely containment, AMR is likely to cause nearly 10 million deaths by 2050 and resulting in significant economic losses. It would also impact nutrition security, livelihood and hinder the attainment of the Sustainable Development Goals. In 1928, penicillin was developed and socalled magic drug was subsequently commercialised and used globally. When antibiotic resistance ?rst emerged, novel antibiotics to treat these bacteria were developed. However, it is dif?cult to develop effective new antibiotics every time as it is time consuming and costly and if developed a new resistance mechanism emerges in bacteria. There is a demand for new strategies to treat bacterial infections, such as endophytes therapy, phage therapy, antimicrobial peptides, CRISPER cas and so on.

Introduction
Antimicrobial resistance (AMR) has become a major worldwide health issue, requiring the search for natural, safe, and efficient substitutes for synthetic antibiotics. The ancient medical system known as Ayurveda lists a variety of polyherbal compositions having jwaraghna (antipyretic) and krimighna (antimicrobial) qualities. A traditional decoction preparation that is frequently prescribed for microbial infestations (krimi), wound infections, fevers, and skin conditions called Nimbadi Kwatha.Strong herbs that have been separately shown to have antibacterial and immunomodulatory properties, including Nimba (Azadirachta indica), Guduchi (Tinospora cordifolia), Triphala (Haritaki, Bibhitaki, Amalaki), Vasa (Adhatoda vasica), and Katuki (Picrorhiza kurroa), make up Nimbadi Kwatha. Triphala has antimicrobial and antioxidant qualities, Guduchi boosts host immunity and has antibacterial qualities, and Neem provides broad-spectrum antibacterial, antifungal, and antiviral activity. According to experimental studies, giloy extracts are effective against a variety of pathogens, such as bacteria, viruses, and fungi. It has a distinct antimicrobial activity that involves two mechanisms: it enhances phagocytosis, changes cytokine production, and activates macrophages. In light of antimicrobial resistance (AMR), T. cordifolia is a prospective option for the development of plant-based antimicrobials and integrated therapies. Its use is backed by both modern pharmacological research and ethnomedicinal history for infectious disorders and immune health. Nimbadi Kwatha and its derivatives, including Nimbadi Ubatan and soap formulations, have been shown to have antibacterial properties by modern pharmacological research, which also showed a notable inhibition of bacterial and fungal growth in vitro. These results demonstrate the value of Ayurveda in treating infectious diseases and lend credence to its traditional claims. To close the gap between traditional knowledge and contemporary evidence, a thorough analysis of Nimbadi Kwatha’s antibacterial impact is essential. It also identifies the plant’s potential as a natural remedy for drug-resistant infections.

Introduction
The discovery and widespread use of antibiotics in the mid-20th century marked a transformative era in modern medicine, enabling life-saving interventions in surgery, transplantation, and critical care. Diseases once considered fatal became manageable, and the global burden of infectious diseases significantly declined. However, the remarkable success of antibiotics has been increasingly overshadowed by the rapid rise of antimicrobial resistance (AMR), now recognized by the World Health Organization (WHO) as one of the most serious threats to global health, food security, and sustainable development. Resistant infections already contribute to longer hospital stays, increased healthcare costs, and elevated mortality rates. Alarmingly, if current trends continue, AMR-related deaths are projected to exceed those caused by cancer by 2050.A pivotal yet often underestimated factor in the persistence and spread of AMR is the formation of microbial biofilms. Biofilms are highly organized, surface-attached communities of microorganisms embedded in a self-produced extracellular polymeric substance (EPS) composed of proteins, polysaccharides, lipids, and nucleic acids. This matrix not only anchors microbial population but also confers protection against environmental stressors, immune responses, and antimicrobial agents. Bacteria within biofilms can withstand antibiotic concentrations up to 1000 times higher than their planktonic counterparts due to altered metabolic states, enhanced horizontal gene transfer, and activation of resistance mechanisms such as efflux pumps. Biofilms are implicated in over 80% chronic and device-associated infections, including those caused by ESKAPE pathogensAcinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus. These infections are notoriously difficult to treat and often recur, posing significant clinical challenges. Beyond healthcare settings, biofilm formation in livestock and agricultural environmentsexacerbated using antibiotics as growth promoterscontributes to the emergence of resistant strains that can spread to humans via direct contact, environmental contamination, or the food chain.Understanding the multifaceted resistance mechanisms within biofilms is essential for developing effective containment strategies. These include physical exclusion of antibiotics by the EPS matrix, metabolic dormancy, persister cell formation, quorum sensing-mediated coordination, and stress response activation. Moreover, biofilms often consist of multispecies communities, where interspecies interactions further enhance resilience.In response, antibiofilm agents have emerged as a promising frontier in AMR containment. These include natural compounds (e.g., antimicrobial peptides, essential oils), engineered materials (e.g., nanoparticles, surface coatings), quorum sensing inhibitors, efflux pump blockers, and enzymatic disruptors such as dispersin B and DNases. Ecological approaches like probiotics and positive biofilms offer preventive strategies in agriculture and food systems. Importantly, these agents aim to complement antibiotics by enhancing their efficacy rather than replacing them.Despite challenges in scalability, safety, and regulatory approval, antibiofilm strategies represent a paradigm shift in infection control. Their integration into clinical, veterinary, and environmental practicesaligned with the One Health frameworkis essential for preserving antibiotic effectiveness and mitigating the global AMR crisis.