Epidemiology of Antimicrobial Resistance (AMR)

Antibiotics are antibacterial compounds produced sometimes by bacteria, and also synthesized artificially sometimes like Penicillin, the first natural antibiotic but there are antibiotics like dynamites which are semisynthetic ones.

Antimicrobial is a broad term covering antibiotics, anti-parasitic agents, antiviral compounds and antifungals.

Things like inadequate dosage and over-the-counter (OTC) availability of antibiotics have made antimicrobial resistance a global problem now.

Some compounds are antibiotics but also act as anti-parasitic agents, like metronidazole (act on anaerobic bacteria as well as gut protozoa) so they have a dual function

Epidemiology of Antimicrobial Resistance (AMR)

Worldwide, over 7 lakh people are losing their lives every year to antimicrobial resistance. This was the reported figure, so the actual figure may be 6-10 times the figure given in fact.

In India, every year one lakh people have died due to road accidents or are prone to cancer. This is an arbitrary- an imaginary figure. Nearly 3-4 lakh people die due to antimicrobial resistance which means infections due to drug-resistant or multidrug-resistant bacteria.

By 2050, AMR will decrease the Global Domestic Product (GDP) by 2 to 3.5%. So, this arises financial affinity not only the health implications and several managerial problems can be checked and also proper AMR if more, results in prolonged illness and longer duration of hospital stay, leading to more cost burden for the patient.

According to WHO, AMR is one of the top 10 global public health threats facing humanity lack of clean water, proper hygiene and sanitation, and inadequate infection prevention and control promote the spread of antibiotic-resistant microbes (also termed bugs and superbugs).

According to a survey, a lot of people die due to AMR, one child dies every nine minutes and around 80,000 people are infected by drug-resistant TB in 2015. So, AMR concern all the microbes and all the disease but it is especially prevalent in a few gram-negative bacteria such as mycobacterium tuberculosis, and staphylococcus, which are common in any scenario. WHO has designated AMR as an immediate and urgent priority. We all need to work together to reduce the menace of AMR. One needs to work together to emphasize the team. The message for this World’s Antibiotic Awareness Week is that come forward and prevent the emergence of the burden of AMR and try to mitigate it.

Why AMR is such a crisis now? Because of antibiotic resistance is mostly attributed to several factors:

•         The overuse and misuse of antibiotics as well as
•       A lack of new drug development by the pharmaceutical industry due to reduced economic incentives and challenging regulatory requirements. So, a drug has a lot of force and a lot of time then several trials have to go in animal models or other trials, safety issues or safety trials, efficacy trials and only then it can enter the market by the time it enters the market it will encounter a large number of robust drug-resistant microbes.
•         Easy availability
•         Prescription of antibiotics by quacks and other unqualified persons.
•          a Sufficient number of new antibiotics classes are not coming up. In 2019, WHO identified 32 antibiotics in clinical development addressing the WHO list of priority pathogens, of which only six were classified as innovative and the rest are modifications of existing ones.
•         Bacteria have developed some smart strategies to overcome antibiotic resistance like biofilms wherever the bacteria have biofilms, they will form a layered sheet like a layer of eggs are problematic matrix and all the microcolonies. And this will firstly not allow the bacteria antibiotic to penetrate the bacteria and reach its target of action. And secondly, even if the bacteria enter through these variants, they will be flung out through influx forms, the efflux pumps are also there, gene-mediated resistance via plasmids and episomes and others.
•         Most healthcare facilities do not have or do not implement antibiotic stewardship policies.

What is AMR?

Resistance of a microorganism to an antibiotic that was originally effective in treating infections caused by it. This is AMR, so that means there is a problem with bacteria, there is a problem with viruses, and fungi and India’s bacterial disease burden is the highest among the world’s largest population. The large population suffers from diseases like diabetes, and cardiac disease, 40% of the children are malnourished and other risks of infections and more and more drug-resistant bacteria are being identified. Why does one face such a stiff challenge from AMR in India? One study published in the lancet Regional Health- Southeast Asia, examined antibiotics use in India and found that India consumes a high volume of broad-spectrum which should ideally be used sparingly. In India, if one doesn’t consume it in proper doses, a large number of drugs would become inefficient or inefficacious in treating a large number of infections after any point in time. So instead of that one should go for a narrow-spectrum antibiotic for initial use. And there are some stark gaps in infection prevention and control (IPC) practices, and the high burden of communicable diseases also. So, there is one specific metal activist called NDM or New Delhi Pomellato-beta lactamase activist that was discovered in 2009 in a patient who migrated to Sweden from India it was found equally, and this is perhaps a controversial issue, but it was possibly found first in India in E. coli and Klebsiella pneumonia. According to a survey it was found that the death rate in South Asia, Southeast Asia and Sub-Saharan Africa is high and comparatively low in Central Europe, Eastern Europe and Central Asia, Latin America and the Caribbean, North Africa and the Middle East. There are several factors which contribute to the economic crisis, political instability or socioeconomic status. Many factors go hand in hand to cause such a picture. India carries one of the largest burdens of drug-resistant pathogens worldwide. Like the highest burden of multi-drug resistant tuberculosis (TB) alarmingly high resistance among gram-negative and gram-positive bacteria even to newer antimicrobials such as carbapenems and faropenem. Even environmental and veterinary-derived strains are highly antibiotic-resistant in India. Powerful drugs like newer generation cephalosporins are sold far more frequently in India for no apparent reason-between 2005 and 2009, sales of cephalosporins increased by 60%. So, it is the most abused antibiotic during wartime. Azithromycin is one among them.  it has been used for covid super secondary prevention of infections in covid or treatment of secondary infections or even it can target to kill SARS coronavirus too. Probably it does, but it has led to some abuses of this antibiotic and other regulatory issues are also they are like antibiotic-related laws which are not always enforced strictly in India. This is a great area which needs to be focused on. Antibiotic laws are not always possible to be enforced strictly and in such a huge population and there are not enough monitoring or pharmacovigilance issues are there. The Indian medical representatives play a crucial role in marketing antibiotics and pharmaceutical drugs. These quacks, in turn, unwillingly speed up the creation of superbugs by offering incomplete or unnecessary antibiotic treatments. 

Resistance Mechanisms of Bacteria 

They can modify or thicken cell walls (VISA), develop biofilms (preventing entry via thick EPM), have efflux pumps and modify target sites (like aminoglycosides) or modify/ alter the antibiotics (like aminoglycosides), beta-lactamase and ESBL, along with other ways.

ESKAPE group of bacteria are most important concerning AMR, like enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species.

WHO list of Priority Pathogens

World Health Organization (WHO) has published a list of priority pathogens which need to be managed very carefully, and how they should be noted or notified. This data was released in 2017. And many pathogens in this list are highlighted below:

Priority 1: CRITICAL

Acinetobacter baumannii which is often carbapenem-resistant

Pseudomonas aeruginosa, carbapene resistant

Enterobacteriaceae, carbapenem-resistant, 3rd generation cephalosporin-resistant

Priority 2: HIGH

Enterococcus facecium, vancomycin-resistant

Staphylococcus aureus, methicillin-resistant, vancomycin

Helicobactor pylori, clarithromycin-resistant

Campylobacter, fluoroquinolone-resistant

Salmonella spp, fluoroquinolone-resistant

Priority 2: MEDIUM

Streptococcus pneumonia, penicillin-non-susceptible

Haemophilus influenza, ampicillin-resistant

Shigella spp, fluoroquinolone-resistant

 Problem with Super Bugs

With MDR TB coming up, the problem escalates and mounts.

Now, it will also be very difficult to contain pneumonia, tuberculosis, gonorrhoea and Salmonella infections.

For common bacterial infections, including urinary tract infections, and sepsis, resistance against antibiotics used to treat these infections has been observed worldwide.

This shows that there is a scarcity of effective antibiotics. The stock is deficit and flooding dry. The usage of new drugs along with judicious usage of the existing drugs and prevent misuse or not using it whenever it is not needed.

Tryst with AMR

• In vitro nitrofurantoin resistance in E. coli in CA-UTI is worrisome (more than 10%).
• In vitro Ciprofloxacin resistance in E. coli in CA-UTI is also a problem.
• Candida isolates from UTI are still mostly susceptible to Fluconazole.

Solution 

Antibiotic stewardship and broadly antimicrobial stewardship (AMS) can guide in the proper use and prevent misuse.

Antimicrobial Stewardship (AMS) by definition, measures all steps to be taken to minimize abuse and promote judicial usage and adverse effects of antimicrobials.

Antibiotic Stewardship

• Enhancing infection prevention and control
• Controlling the source of infection
• Prescribing antibiotics when they are truly needed
• Prescribing appropriate antibiotics with adequate dosages
• Using the shortest duration of antibiotics based on evidence
• Reassessing treatment when culture results are available
•  Supporting surveillance of AMR and HAIs and monitoring of antibiotic consumption
•  Educating staff
• Supporting an interdisciplinary approach

Examples of Misuse of Antibiotics

• Nitrofurantoin for upper UTI (does not attain therapeutic concentration in upper UTI)
• Vancomycin for gram-negative bacterial infections (intrinsically resistant almost always)
• Irrational antibiotic combinations and using 2 classes of beta-lactams together (like Ampicillin with Meropenem).

Rationale Use Needed

• Usage recommended in proper dosage.
• Common cold (due to virus) and most diarrhoea (due to virus) do not require antibiotics.
• Clinicians should try to administer antibiotics only after getting antibiotic susceptibility results from the lab if lab support is available. 
• Escalate and de-escalate the matter judiciously.
• Use the narrowest spectrum of antibiotics for urgent empirical use.

Other Things to do

Two institutions in India’s Ministry of Health: The Indian Council of Medical Research (ICMR) and the National Centre for Control (NCDC), each have developed National networks of public and private hospitals to measure AMR trends, prevent healthcare-associated infections (HAIs), and promote appropriate use of antibiotics.

• One health approach is the need for this is rampant in the veterinary sector misuse. These discarded effluents and other things are contaminating the water, and the soil and are found in groundwater, open air defecation contaminates surface water, and one may consume it inappropriately or inadvertently and then it will again cause transmission of superbugs to one and cause diarrhoea and other diseases.
• Antibiotic ward rounds.
• National Action Plan (NAP) for antimicrobial resistance in India (2017-2021 release). The government has released a few of them like there are some strategic priorities.

Strategic Priorities in NAP:

There are six such priorities:

• Improve awareness and understanding of AMR through effective education, communication and training more and more webinars and such workshops need to be conducted with hands-on training to be given.
• Strengthen knowledge and evidence through surveillance.
• Reduce the incidence of infection through effective infection, prevention and control which also includes vaccination whenever required.
• Optimize the use of antimicrobial agency, health, animals and food.
• Promote investments for AMR activities, research and innovation.  
• Strengthen India’s leadership on AMR.

The Focus Areas of the Six Strategic Priorities of NAP-AMR

•   Improve awareness and understanding of AMR through effective communication, education and training
• Strengthen knowledge and evidence through surveillance.
• Reduce the incidence of infection through effective infection prevention and control, in healthcare.