Antimicrobial Resistance

Antimicrobial resistance (AMR) refers to the ability of microorganisms—such as bacteria, viruses, fungi, and parasites—to resist the effects of antimicrobial drugs that were previously effective against them. This resistance renders standard treatments ineffective, allowing infections to persist, spread, and increase the risk of severe illness or death. AMR has become a global public health threat, undermining the advances of modern medicine and posing significant social and economic challenges.

Background and Concept

The discovery of antibiotics in the early twentieth century, beginning with Alexander Fleming’s identification of penicillin in 1928, revolutionised medical treatment by enabling effective control of bacterial infections. However, Fleming himself warned of the potential for resistance if antibiotics were misused.
Over time, the widespread and often inappropriate use of antimicrobials in humans, animals, and agriculture has accelerated the natural process of microbial adaptation. Microorganisms evolve through mutation or by acquiring resistance genes from other microbes, resulting in strains that can survive even high doses of drugs designed to kill them.
Antimicrobial resistance is not confined to bacteria (antibiotic resistance) but also includes:

• Antiviral resistance (e.g., HIV and influenza viruses)
• Antifungal resistance (e.g., Candida auris)
• Antiparasitic resistance (e.g., Plasmodium falciparum causing malaria)

Mechanisms of Resistance

Microorganisms employ several biological mechanisms to resist antimicrobial agents, including:

• Enzymatic degradation: Production of enzymes such as β-lactamases that destroy antibiotic molecules (e.g., penicillin resistance).
• Target modification: Alteration of the drug’s target site so that the antimicrobial can no longer bind effectively (e.g., changes in ribosomal binding sites).
• Efflux pumps: Bacteria expel the drug from their cells using specialised proteins.
• Reduced permeability: Alteration of cell membranes to prevent drug entry.
• Gene transfer: Horizontal transfer of resistance genes via plasmids, transposons, or bacteriophages among microbial populations.

These mechanisms enable resistant strains to multiply and spread rapidly, particularly in healthcare settings and densely populated environments.

Causes and Contributing Factors

AMR arises primarily from human activities that exert selective pressure on microorganisms. Major contributing factors include:

• Overuse and misuse of antimicrobials: Excessive prescription, self-medication, and use of broad-spectrum antibiotics for viral infections such as the common cold.
• Incomplete treatment courses: Stopping medication prematurely, allowing partially resistant organisms to survive and multiply.
• Use of antibiotics in agriculture and animal husbandry: Routine use of antibiotics as growth promoters or preventive agents in livestock fosters resistance that can transfer to humans through the food chain.
• Poor infection prevention and control: Inadequate sanitation, hygiene, and hospital infection control measures facilitate the spread of resistant microbes.
• Lack of new drug development: Pharmaceutical innovation has slowed, resulting in a shortage of novel antibiotics to replace those rendered ineffective.

Global travel and trade further accelerate the dissemination of resistant strains across borders, turning local problems into global threats.

Major Resistant Pathogens

The World Health Organization (WHO) identifies several priority pathogens that pose the most serious threat to human health due to resistance, including:

• Methicillin-resistant Staphylococcus aureus (MRSA)
• Vancomycin-resistant Enterococci (VRE)
• Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae
• Carbapenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa
• Multidrug-resistant Mycobacterium tuberculosis (MDR-TB)
• Drug-resistant Neisseria gonorrhoeae

In addition to bacterial resistance, the emergence of antifungal resistance (notably in Candida auris) and antiviral resistance (as seen in HIV and influenza) has raised global concern.

Impact on Public Health and Society

The consequences of AMR are severe and multifaceted:

• Treatment failure: Common infections such as pneumonia, urinary tract infections, and sepsis become difficult or impossible to treat.
• Increased mortality and morbidity: WHO estimates that AMR causes nearly five million deaths annually, either directly or indirectly.
• Longer hospital stays and higher costs: Resistant infections require extended treatment, expensive second-line drugs, and additional medical resources.
• Threat to modern medicine: AMR undermines procedures such as organ transplantation, chemotherapy, and major surgeries that rely on effective infection control.
• Economic burden: Global economic losses from AMR could reach USD 100 trillion by 2050 if unaddressed, according to the Review on Antimicrobial Resistance (2016).

Global Response and Initiatives

Recognising AMR as a critical global issue, several coordinated initiatives have been developed:

• Global Action Plan on Antimicrobial Resistance (WHO, 2015): Outlines strategies to improve awareness, strengthen surveillance, reduce infection incidence, and promote sustainable drug use.
• One Health Approach: Emphasises the interconnectedness of human, animal, and environmental health, advocating coordinated action across all sectors.
• Global Antimicrobial Resistance Surveillance System (GLASS): Facilitates international data sharing and monitoring of resistance trends.
• United Nations and G20 Declarations: Commit member nations to implement policies against AMR, including research funding and regulation of antimicrobial use.

International organisations such as the Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (WOAH) play vital roles in managing AMR in agriculture and animal health.

National Response in India

India faces a particularly high burden of AMR due to its large population, high infection rates, and widespread antibiotic use. In response, the government launched several initiatives:

• National Action Plan on Antimicrobial Resistance (NAP-AMR) 2017–2021: Based on WHO’s global framework, focusing on awareness, surveillance, rational use, and infection prevention.
• National Programme on Containment of AMR (2012): Established laboratory networks and surveillance systems across hospitals.
• Schedule H1 under the Drugs and Cosmetics Rules (2014): Restricts over-the-counter sales of critical antibiotics, requiring prescription-based dispensation.
• AMR Surveillance and Research Network (AMRSN): Operated by the Indian Council of Medical Research (ICMR) to collect and analyse resistance data.
• Kayakalp and Swachh Bharat Mission: Promote hospital hygiene and sanitation to prevent infection spread.

India has also initiated collaborations with global partners under the One Health framework to monitor resistance in humans, animals, and the environment.

Prevention and Control Strategies

Tackling antimicrobial resistance requires a multi-sectoral and sustainable approach involving governments, healthcare providers, industry, and the public. Key strategies include:

• Rational use of antimicrobials: Prescribing antibiotics only when necessary and using narrow-spectrum agents whenever possible.
• Infection prevention and control (IPC): Strengthening hospital hygiene, sterilisation, and isolation procedures to reduce infection spread.
• Vaccination: Reducing disease incidence through immunisation, thereby lowering the need for antibiotics.
• Antimicrobial stewardship programmes: Institutional frameworks to monitor antibiotic use and resistance patterns in healthcare facilities.
• Public education: Raising awareness about the dangers of misuse and the importance of completing prescribed treatments.
• Research and innovation: Encouraging pharmaceutical companies and academic institutions to develop new antimicrobials, vaccines, and diagnostic tools.
• Environmental regulation: Monitoring and controlling antimicrobial waste from pharmaceutical industries and agriculture.

The One Health Approach

The One Health approach is central to AMR containment, recognising that human, animal, and environmental health are interlinked. Resistance genes can move between ecosystems—through water, soil, and food chains—necessitating integrated policies that address:

• Rational antibiotic use in veterinary medicine and aquaculture.
• Safe handling of animal waste and agricultural runoff.
• Surveillance of resistance in wildlife and environmental reservoirs.

Future Challenges

Despite global awareness, AMR continues to expand due to inadequate implementation, weak surveillance, and limited access to diagnostics. Developing countries face the dual challenge of ensuring access to essential medicines while curbing their misuse.
The COVID-19 pandemic exacerbated the problem, as antibiotics were often prescribed inappropriately for viral infections, further increasing resistance rates. Additionally, few new antibiotic classes have been developed in recent decades, creating an urgent need for innovative drug discovery and alternative therapies.