Antimicrobial Resistance (AMR)

“Without urgent action we are heading for a post-antibiotic era, in which common infections and minor injuries can once again kill.” – WHO

Why in news?

Kerala – the first state to adopt a comprehensive policy on AMR in 2016 to fight growing antibiotic resistance – is now taking a big leap.

What is AMR?

• Antimicrobial resistance occurs when microbes (bacteria, viruses, fungi and parasites) become resistant to antimicrobial drugs (such as antibiotics, antifungals, antivirals, antimalarials, and anthelmintics).
• As a result, the medicines become ineffective and infections persist in the body, increasing the risk of spread to others.
• Microorganisms that develop antimicrobial resistance are sometimes referred to as “superbugs”.
• While antibiotic resistance specifically covers resistance to antibiotics, antimicrobial resistance is a broader term that also covers drugs that are used to treat conditions caused by other microbes, including parasites, fungi, and viruses. These conditions include malaria, HIV, and candida.

What causes Antimicrobial resistance

• Misusing antibiotics breeds drug resistance among the bacteria that normally live in our bodies – even though these bacteria are harmless, they can pass resistance on to other, more dangerous species.
• Antibiotic resistance occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections. The bacteria survive and continue to multiply causing more harm.
• An antibiotic targets a particular characteristic of the infectious bacteria, so by specifically killing all bacteria that have this characteristic, any that happen not to have it gain an advantage and are left free to multiply and spread. This creates a population of resistant bacteria that cannot be killed by that antibiotic.
• The term drug-resistant infections makes it clearer that it is the infectious species that is resistant to drug not the patient.

Antimicrobial Resistance in India: Scoping Report on Antimicrobial Resistance in India

The report was prepared for Department of Biotechnology and Research Councils United Kingdom (RCUK) by the Center for Disease Dynamics, Economics & Policy, India (CDDEP).

According to the Report:

• In 2014, India was the highest consumer of antibiotics, followed by China and the United States. However, the per capita consumption of antibiotics in India is much lower than in several other high income countries.
• India has some of the highest antibiotic resistance rates among bacteria that commonly cause infections in the community and healthcare facilities.
• Resistance to carbapenem class of antibiotics (the group of antibiotics available against antimicrobial resistant pathogens) was the highest.
• There is an increasing trend of antibiotic resistance among neonates.

Concerns due to Antimicrobial Resistance

1. Due to growing resistance of pathogens to antimicrobial drugs we are losing our first-line antibiotics making a broad range of common infections much more difficult to treat.
2. Second- and third-choice antibiotics are more costly, more toxic, need much longer durations of treatment, and may require administration in intensive care units.
3. Diseases like smallpox that have been eradicated may come back.
4. The infection are becoming more difficult to treat, giving rise to new forms of previously treatable disease:

• Multidrug-resistant typhoid fever is affecting parts of Asia and Africa.
• Only 50% of all patients with multi-drug resistant tuberculosis can be cured.
• Resistance is an emerging concern for treatment of HIV infection.
• In the case of malaria, spread of artemisinin resistant strains, or the independent emergence of artemisinin resistance in other regions, could jeopardize important recent gains in malaria control.
• Gonorrhoea, a sexually transmitted disease, is now resistant to multiple classes of drugs.

5. Organ transplantation, joint replacements, cancer chemotherapy, and care of pre-term infants, will become more difficult or even too dangerous to undertake.

6. The British government commissioned a series of reports on AMR, estimating that by 2050, as many as 10 million people could die annually from AMR complications.

7. The economic impact of “superbug” outbreaks could top $100 trillion; low-income countries would suffer disproportionately.

8. Fewer inventions of new antibiotics in last two decades due to lack of R&D and high cost of investments,  making increasing resistance to available drugs a concern.

9. New resistance mechanisms, such as the New Delhi metallobeta-lactamase NDM-1, have emerged among several gram-negative bacilli.

Note: New Delhi metallo-beta-lactamase 1 (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections.

10. “Nosocomial infections” or, “Hospital-associated infections” can involve some pathogenic bacteria that developed resistance to antibiotics:

•  Staphylococcus aureus resistant to methicillin,
• Enteroccocci resistant to vancomycin causing heart valve infections,
• Acinetobacter baumannii resistant to carbapenems producing surgical site and wound infections.

11. Resistance to last resort antibiotics on rise:

• Resistance to carbapenem class of antibiotics, one of the last-resort antibiotics to treat serious bacterial infections in humans, among various gram-negative bacteria is on rise.
• With increasing use of Colistin, last resort antibiotic in human medicine, for treatment of carbapenem-resistant gram-negative bacterial infections, Colistin resistance among gram-negative bacteria has emerged in India .

Major Reasons for spread of Antimicrobial Resistance

• Antibiotic Consumption: The main origin of resistance to antibiotics is their misuse. As underlined by the European Centre for Disease Prevention and Control (ECDC) there are three main types of misuse:
• The unnecessary prescription of antibiotics for viral infections like flu, influenza, against which they have no effect;
• The too frequent prescription of “broad-spectrum antibiotics”, in place of a better targeted antibiotic, through more precise diagnosis;
• The inadequate use by the patient, not respecting either dosage or duration of the treatment, which means that some of the bacteria may survive and become resistant.
• Indiscriminate use of antibiotic FDCs even without the knowledge of a proven advantage over single compounds, leading to emergence of bacterial strains resistant to multiple antibiotics. Approximately 118 antibiotic FDCs are available in India.

2. Social factor: Among the general public, social factors include self-medication, access to antibiotics without prescription, use of pharmacies and informal healthcare providers as sources of healthcare, and lack of knowledge about when to use antibiotics. the practice of Over-The -Counter (OTC) dispensation of antibiotics without any prescription is common.
3.  Animal Protein: Although direct antibiotic sales data in food animals are not available for India, it is estimated that India was the fifth-largest consumer of antibiotics in food animals (poultry, pigs, and cattle) in 2010. Antibiotics such as colistin, tetracycline, doxycycline, and ciprofloxacin, which are critical to human health, are commonly used for growth promotion in poultry
4. Cultural Factors:

• One of the major cultural activities associated with potential acquisition and spread of antibiotic-resistant bacteria is mass bathing in rivers as part of religious mass gathering occasions.
• For example, according to a study, Mass-bathing in the Ganga during pilgrimages may be contributing to anti-microbial resistance (AMR)

5. Pharmaceutical Industry Pollution:

• The wastewater effluents from the antibiotic manufacturing units contain a substantial amount of antibiotics, leading to contamination of rivers and lakes.
• In India, the Central Pollution Control Board (CPCB) established effluent standards for pharmaceutical industry waste, and all state pollution control boards use the same standards. The current standards do not include antibiotic residues, and thus they are not monitored in the pharmaceutical industry effluents

6. Sanitation:

• Poor sanitation plays a major role in the spread of antibiotic-resistant bacteria and ARGs. According to the World Bank, more than 50% of the Indian population does not have access to sanitation facilities for safe disposal of human waste (World Bank 2017).
• In addition, a large proportion of sewage is disposed untreated into receiving water bodies, leading to gross contamination of rivers with antibiotic residues, antibiotic-resistant organisms

7. Poor Infection Control Practices in Healthcare system:

• The prevalence of various health care associated infections (HAIs) among Indian hospitals ranges from 11% to 83%, in contrast to the WHO estimate of about 7% to 12%.
• This is primarily poor infection control practices. For example, a study in Mangalore which assessed hand-washing practices of nurses and doctors, found that only 31.8% of them washed hands after contact with patients.

1. Chennai Declaration:

• Formulation of an effective national policy to control the rising trend of antimicrobial resistance,
• A ban on the over-the-counter sale of antibiotics,
• Changes in the medical education curriculum to include training on antibiotic usage and infection control
• Setting up of a National Task Force to guide and supervise the regional and State infection control committees.
• An Infection Control Team (ICT) be made mandatory in all hospitals.
• Regulatory authorities and accreditation agencies such as the National Accreditation Board for Hospitals and ISO must insist on a functioning ICT during the licensing and accreditation process
• National Accreditation Board for Hospitals & Healthcare Providers (NABH) insist on strict implementation of hospital antibiotic and infection control policy, during hospital accreditation and re-accreditation processes.

Actions Taken Under Chennai Declaration

• To meet the obligations of the declaration, the National Programme on Containment of Antimicrobial Resistance was launched under the 12th Five-year Plan.
• The Drugs and Cosmetic Rule, 1945 were amended in 2013 to incorporate a new Schedule H1.  It contains certain 3rd and 4th generation antibiotics, certain habit forming drugs and anti-TB drugs. This rule is meant to regulate over-the counter dispensing of drugs. Pharmacists not only have to insist on a prescription from a registered medical practitioner, but they also need to enter details in a register. Drug inspectors will monitor compliance. First-line antibiotics will not come under the strict monitoring as those are excluded from the list, at least initially. The new H1 list is based on a step-by-step strategy of Chennai declaration
• Under the Drugs & Cosmetics Rules, drugs specified under Schedule H and Schedule X are required to be sold by retail on the prescription of a Registered Medical Practitioner only.

2. National Action Plan on Antimicrobial Resistance- Delhi Declaration

The plan calls for coordinated efforts by government agencies involving health, education, environment, and livestock to change prescription practices and consumer behaviour and to scale up infection control and antimicrobial surveillance.

The objectives of the plan include:

• To establish a laboratory-based surveillance system by strengthening laboratories
• To generate quality data on AMR for pathogens of public health
• To generate awareness among healthcare providers and in the community regarding the rational use of antibiotics
• To strengthen infection control guidelines and practices and promote rational use of antibiotics

3. Red Line Campaign on Antibiotics 2016: The campaign  was launched to:

• Raising awareness about how to identify a drug that should be dispensed only with a prescription from a licensed doctor
• Limiting the practice of self-medication
• Making the public aware of the potential harms that may result from the misuse of antibiotics.

4. In 2017, FSSAI released certain guidelines limiting the antibiotics in food products such as fish and honey- The Food Safety and Standards (Contaminants, Toxins and Residues) Regulations in food animals.

5. Kerala became the first state to adopt a comprehensive policy on AMR in 2016, which is now being implemented comprehensively . To curb anti-microbial resistance (AMR), government has prepared an all-inclusive action plan involving human health, animal, food and environment.

International Initiatives:

Global Action Plan on AMR:

1. The May 2015, World Health Assembly of WHO adopted a global action plan on antimicrobial resistance, which outlines five objectives:

• to improve awareness and understanding of antimicrobial resistance through effective communication, education and training;
• to strengthen the knowledge and evidence base through surveillance and research;
• to reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures;
• to optimize the use of antimicrobial medicines in human and animal health;
• to develop the economic case for sustainable investment that takes account of the needs of all countries and
• to increase investment in new medicines, diagnostic tools, vaccines and other interventions.

2. In 2017, WHO launched new guidelines on use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antibiotics routinely to promote growth and prevent disease in healthy animals. These guidelines aim to help preserve the effectiveness of antibiotics that are important for human medicine by reducing their use in animals.

3. WHO has also grouped antibiotics into three categories – ACCESS, WATCH and RESERVE – with recommendations on when each category should be used. Initially, the new categories apply only to antibiotics used to treat 21 of the most common general infections.

• The change aims to ensure that antibiotics are available when needed, and that the right antibiotics are prescribed for the right infections. It should enhance treatment outcomes, reduce the development of drug-resistant bacteria, and preserve the effectiveness of “last resort” antibiotics that are needed when all others fail.

Way Ahead:

Infection Prevention and control within health-care facilities:

• Establishing an infection prevention and control committee (IPC).
• Good hand hygiene practices.
• Effective diagnosis and treatment of infection.
• Rational antimicrobial use.
• Surveillance of antibiotic resistance and antibiotic use.
• Improving the antimicrobial quality and supply chain.
• Good Microbiology Practices.

Innovation in new Drug and Technology:

• Concerns of increased antibiotic resistance lead to the urgent need of concentrating on the issue of new drugs and vaccines development to combat AMR. Collaborated efforts of national, international, government and academic networks are needed to identify new classes of antibiotics and diagnostic technologies.
• For example, the EU, the UK, the US and Canada have moved forward on projects to fill knowledge gap by directly funding basic and clinical research by scientists; working with pharmaceutical companies; and offering monetary prizes for new diagnostics needed to use antibiotics more responsibly

Awareness:

• Educate and aware people to ensure rational use of antimicrobial drugs. Further, health-care practitioners should not prescribe or dispense antibiotics unless they are truly necessary.
• Awareness on not prescribing antibiotics for common viral infections, pharmacists selling antibiotics over the counter and a few precautions for hospital-based workers — using a hand rub before and after examining the patient, for instance — will go a long way in controlling the spread of resistant bugs, as well as hospital-acquired infections.

Agriculture and Livestock:

• It is important to ensure that antibiotics given to animals are used only to control or treat infectious diseases and under veterinary supervision. Last resort” antibiotics should never be used as growth promoters in livestock farming, but achieving this will require significant changes to current practices.

Surveillance:

• Weak surveillance and regulatory system is also an important determinant of antimicrobial resistance. Thus appropriate surveillance mechanisms in the health and veterinary sectors to generate reliable epidemiological information, baseline data, trends on antimicrobial resistance, utilization of antimicrobial agents and impact on the economy and health should be implemented