Education, Infectious Diseases

What is Antimicrobial Resistance (AMR)?

Author Kimberly Hazel , 19-Jul-2022

Table of contents

The World Health Organisation drives World Antimicrobial Awareness Week to improve global knowledge of antibiotic drugs. Running from the 18th to the 24th of November, the awareness initiative is focused on uniting to preserve effective antimicrobials and reduce or prevent the spread of Antimicrobial Resistance (AMR), which is becoming an increasing concern worldwide.

Before we jump deeper into the AMR and the global impact it will have if not addressed, let’s briefly cover the history of antimicrobials in medicine. The term antibiotic was first used professionally by Selman Waksman in 1942 when he defined it as “a substance produced by a microorganism that has the power of inhibiting the growth of another microorganism.” However, the use of antibiotics dates back much further. 

 

A Brief History of Antibiotics

 

The ancient Egyptians used moldy bread to treat infections, and the Greek physician Hippocrates prescribed garlic to treat wounds. In the early 20th century, scientists began to develop synthesized versions of these natural antibiotics. 

 

A Famous Scientist & His Work on Medicines

Dr. Paul Ehrlich is a German-born American scientist who has made numerous significant contributions to the field of medicine, including the development of a treatment for syphilis and the discovery of immunity to diphtheria. In addition to his many medical achievements, Ehrlich also made essential contributions to the fields of immunology and toxicology.  His work has profoundly impacted both medicine and society, and he is rightly considered one of the most influential scientists of our time. 

Dr. Ehrlich’s groundbreaking work has helped to save countless lives and has dramatically improved our understanding of the human body and its response to disease. He noted that certain dyes would color bacterial cells but not others. Ehrlich thought that if these cells could be isolated, selective chemicals could be used to target and neutralize bacteria. He was instrumental in developing the idea of using antibodies to fight disease, and he also pioneered the use of equilibrium dialysis in toxicology. 

The word antibiotic means “against life.” Ehrlich first used the term casually in the early 1900s while he searched for a substance that could kill bacteria without harming the body’s cells. In 1909, he and his colleague Sahachiro Hata announced the discovery of the first proper antibiotic, salvarsan. Salvarsan came from the toxic element arsenic. Salvarsan, now known as arsphenamine, was the ‘drug of choice’ to treat syphilis until the 1940s. 

 

The Antibiotic that Changed the World

Treatment of syphilis with Salvarsan was superseded by the most famous antibiotic of them all – penicillin. Early observations of penicillin properties were made by William Roberts and Louis Pasteur during the close of the 19th century however, it was not until 1928 that Sir Alexander Fleming made a revolutionary discovery. 

Fleming discovered that the mold killed and prevented the growth of bacteria. He deduced that the mold must create a specific substance and named this ‘mold juice’ penicillin. Penicillin is derived from a fungus called Penicillium chrysogenum, and it proved to be a highly effective treatment for bacterial infections.  

This first antibiotic was not isolated and purified until 1942 by two Oxford scientists, Ernst Chain and Howard Florey – who shared the 1945 Noble Prize in Medicine with Fleming. Over the next several decades, several other antibiotics were discovered, including streptomycin, tetracycline, and chloramphenicol. These created an arsenal for use against several major diseases.  Today, they are an essential part of modern medicine.

 

Antimicrobials: More Than Just Antibiotics

Antimicrobials are a broad class of agents that kill or inhibit the growth of microbes, including bacteria, viruses, fungi, and protozoans. They can be used to treat both viruses and bacteria, and they work by killing or inhibiting the growth of the microbes. 

 

Antimicrobials are a vital tool in medicine, effectively treating many infections. They can also be used in food preparation and preservation to prevent the growth of harmful microbes. In general, antimicrobials are safe and effective when used as directed.

 

Common Antibiotics and Their Uses

Antibiotics are a type of antimicrobial that explicitly targets bacteria and are used to treat bacterial infections. They work by killing bacteria or preventing them from growing. Many different types of antibiotics are available, each effective against a specific type of bacteria. 

Some common antibiotics include amoxicillin, erythromycin, and penicillin. Antibiotics are typically taken orally as pills or capsules but can also be given intravenously. Common side effects of antibiotics include nausea, vomiting, and diarrhea. More severe side effects are rare but can include allergic reactions and liver damage. The specific antibiotic that is prescribed will depend on the type of infection that is being treated. 

For example, amoxicillin is often used to treat ear infections. It is also used to treat urinary tract infections. Erythromycin is used to treat respiratory infections. Penicillin is a common antibiotic for treating strep throat, skin, and ear infections. Azithromycin (Zithromax) is an antibiotic used to treat skin infections, pneumonia, and ear infections. Cephalexin (Keflex) is an antibiotic used to treat skin and urinary tract infections.

Antibiotics are ineffective against viruses and often used with other drugs to treat viral infections.  This is why there are many different antimicrobials aside from just antibiotics, and they can be used in various ways, including topically, orally, and intravenously. 

 

Common Antivirals and Their Uses

Antivirals are a class of medication used specifically for treating viral infections. Various antivirals are available on the market today, each with unique benefits.  They are generally most effective when used in the early stages of an infection. They can also prevent infection by using them before exposure to a virus or taking them regularly to prevent outbreaks. 

The most common antivirals are nucleoside analogs, which work by inhibiting the replication of viral DNA. Other popular antivirals include protease inhibitors, which prevent the assembly of new virus particles, and neuraminidase inhibitors, which block the release of viruses from infected cells. 

Some common antivirals include acyclovir, commonly used to treat herpes and chickenpox, and valacyclovir, often used to treat shingles. In addition, several antivirals are specifically designed for children, such as amantadine and oseltamivir

Overuse or misuse of antimicrobials can develop resistance among microbes. The antimicrobial becomes less effective at treating or preventing infections when this happens. 

 

What is Antimicrobial Resistance?

AMR stands for “antimicrobial resistance” – a pathogen adaptation process whereby bacteria, viruses, fungi, and parasites develop defenses that make antimicrobials less and less effective. When a tried and proven medicine is no longer effective at fighting its targeted disease, an alternative is needed, which might take years to develop. 

Antimicrobial resistance is a natural phenomenon that human actions impact. Some actions may promote an avoidable spread of these AMR infections. These actions are things like the inappropriate use of antimicrobial medicines in both healthcare and raising crops or animals. Other actions, including poor water quality, lack of sanitation, and substandard hygiene, have also hastened the spread of antibiotic-resistant infections. 

Ultimately, treatment times are prolonged, increasing the risk of spreading disease and developing complications. A “worst-case scenario”  will result in pathogens ‘outsmarting’ humans, and we are left without drugs needed to cure even the most common bacterial infections.

 

If AMR is the Evil Twin, MDR is the Even More Evil Twin

Multidrug resistance (MDR) is a phenomenon that occurs when pathogenic bacteria develop the ability to resist the effects of multiple drugs, precisely two or more. MDR can occur when bacteria or other microorganisms mutate, resulting in changes to their cell structures that make them less susceptible to the effects of drugs. 

MDR can also occur when microorganisms develop mechanisms to pump drugs out of their cells before they have a chance to take effect. This can happen through various mechanisms. While MDR is a natural phenomenon, it can seriously threaten public health. 

It is a significant problem in the healthcare industry, as it limits the effectiveness of antibiotics and other medications. When bacteria become resistant to multiple antibiotics, treating infections with those drugs becomes difficult or impossible. As a result, patients may experience more prolonged periods of illness and more severe symptoms. In some cases, MDR bacteria can even cause life-threatening infections.

There are several ways to combat MDR, such as developing new drugs or using combination therapies. However, the best way to prevent MDR is to use antibiotics judiciously and only when necessary. This will help to slow down the development of resistance and allow existing drugs to remain effective for longer.

 

 

How Can Pathogens Form Antibiotic Resistance? 

Pathogens are microorganisms that cause disease. They can include bacteria, viruses, and fungi. To survive, they must constantly adapt to their changing environment, including the presence of antibiotics. Over time, these resistant strains can become dominant, leading to a rise in antibiotic-resistant infections. 

There are several ways that pathogens can develop antibiotic resistance. These include:

  • Mutations. These changes to the pathogen’s DNA make it more difficult for the antibiotic to bind to the pathogen and kill it. 
  • Horizontal gene transfer. This is when the pathogen acquires DNA from another microorganism resistant to the antibiotic. 
  • Development of efflux pumps. These are proteins that pump the antibiotic out of the pathogen’s cells before it has a chance to kill the pathogen. 
  • Development of biofilms. These protective layers surround the pathogen and make it more difficult for antibiotics to reach and kill it.

 

 

A mutation is a generic term, and one common mechanism is known as plasmid exchange. This occurs when two bacteria come into contact and exchange genetic material. This process can allow a bacterium to acquire resistance genes from another organism. 

Antibiotic resistance can also arise through the action of enzymes known as beta-lactamases. These enzymes break down the beta-lactam ring, a fundamental structure in many antibiotics. As a result, the antibiotic is rendered ineffective against the bacteria expressing these enzymes. 

 

The question is, why do pathogens do this, and how did we discover it was happening?

 

Why Do Pathogens Develop Resistance?

We first began to see evidence of antibiotic resistance in the mid-20th century. The development of antimicrobial resistance is a complex process that is not fully understood. However, many factors are thought to contribute to the problem. 

One factor is the overuse and misuse of antibiotics. When antibiotics are used unnecessarily, it provides pathogens with more opportunities to develop resistance. Another factor is the widespread use of antibiotics in livestock farming. This allows resistant strains of bacteria to spread through the food supply, increasing the chances that human beings will come into contact with them. Finally, the global nature of travel and trade means that resistant strains can quickly spread worldwide, making it difficult to contain them. 

 

Common Infections and Pathogens

Several pathogens are commonly associated with AMR and MDR infections. These include:

  • Bacteria
  • Viruses
  • Parasites
  • Fungi

 

In addition, some other less common pathogens are also becoming increasingly resistant to antibiotics.

Bacteria Commonly Associated with AMR

A bacteria commonly associated with AMR and MDR infection is Methicillin-resistant Staphylococcus aureus (MRSA) is a type of bacteria resistant to many antibiotics. It is a common cause of skin and soft tissue infections and pneumonia. Those with MRSA infections are 64% more likely to die than people with “normal” infections.

Vancomycin-resistant Enterococcus is also a type of bacteria resistant to the antibiotic vancomycin. It can cause urinary tract infections, bloodstream infections, and endocarditis. Clostridium difficile (also known as C. diff) is another bacteria that can cause diarrhea, abdominal pain, and fever and is often seen in hospital patients who have been taking antibiotics.

One of the most significant bacteria associated with AMR infections is Mycobacterium tuberculosis. It is a species of bacteria that causes tuberculosis (TB), with 10 million cases and 1.5 million related deaths in 2020. Some antibiotics can normally target M. tuberculosis, but drug-resistant strains have developed. These account for half a million infections annually. These strains threaten the progress made in containing the global tuberculosis epidemic.

Klebsiella pneumoniae is a common intestinal bacteria that can cause infections. Resistance to carbapenem antibiotics has spread to all regions of the world when used as a last resort for K. pneumoniae. It is a significant cause of hospital-acquired infections.

The list of common resistant infections doesn’t stop there.

 

Drug Resistance in Viruses  

Viruses are also fighting back; resistance has developed to most antivirals. These even include antiretroviral (ARV) drugs. This is a significant concern for immunocompromised populations where replication and prolonged medication exposure can lead to resistant strains. One virus of significance in the area of AMR infections is HIV

HIV is so important because the emergence of a drug-resistant HIV, known as HIVDR, puts all ARV drugs at risk of becoming partially or wholly inactive. The WHO’s HIV drug resistance program monitors the transmission and emergence of resistance to older and newer HIV drugs around the globe for this exact reason.

 

Parasites Associated with AMR 

Parasites have always been a scary concept, especially to the general public. The emergence of drug-resistant parasites reaffirms the fears. It is also one of the greatest threats to the control of malaria to date. Drug-resistant parasites can lead to increased morbidity and mortality.

Artemisinin-based combination therapies, known as ACTs, are the recommended first-line treatment for malaria. These are prescribed in most malaria-endemic countries. Some resistance to these medications has been seen; however, the ACTs remain highly efficacious.

 

Fungi’s Role in AMR Infections

Fungal infections can be complicated, but in general, we have antifungals that work as a treatment for them. However, the prevalence of drug-resistant fungal infections is increasing. Drug-resistant Candida auris is a common fungal infection. It has resistance to fluconazole, amphotericin B, and voriconazole. As more fungi take a cue from Candida auris, it becomes more difficult to treat fungal infections.

 

The Global Impact of Antimicrobial Resistant Infections

Antimicrobial resistance is a growing global problem. Every year, hundreds of thousands of people die from AMR infections, and the problem is only getting worse. The implications of this are profound. 

 

Deadlier Diseases and Longer Hospital Stays

In a world where bacterial infections are once again deadly, routine procedures like surgery and childbirth could become incredibly dangerous. Infections once easily treatable with antibiotics are becoming increasingly challenging to manage as bacteria become resistant to the drugs used to kill them. 

This means that more people are dying from infections that they would have previously been able to recover from. Each year, antibiotic-resistant infections contribute to tens of thousands of deaths in the United States alone. In addition, antimicrobial resistance leads to more extended hospital stays, higher medical costs, and increasing pressure on healthcare systems. 

Hospitals are particularly vulnerable to the spread of antibiotic-resistant organisms as they bring together large numbers of people with compromised immune systems. In addition, the widespread use of antibiotics in hospitals provides opportunities for resistance to develop. As a result, hospital-acquired infections are a significant concern for patients and healthcare providers.

A Role in Hospital-Acquired Infections

The CDC states that at any given time in the US, at least 1 in 31 hospitalized patients has a healthcare-associated infection, also known as a hospital-acquired infection. The specific role of antimicrobial resistance (AMR) in hospital-acquired infections is complex. First, AMR can increase the severity of an infection by making it more challenging to treat. Second, AMR can cause an infection to spread more easily from person to person. Finally, AMR can make it more difficult to identify and control outbreaks of infectious diseases. 

There are several strategies that hospitals can use to reduce the spread of AMR. First, hospitals should promote the prudent use of antibiotics. This means using antibiotics only when necessary and choosing the most appropriate drug for the task. Second, hospitals should invest in infection control measures and infection preventionist professionals.  Finally, patients can be educated on the importance of completing the entire course of antibiotics even if they feel better. 

 

The Economic Toll

Of course, the impacts of AMR and MDR don’t stop at the patients’ beds. The economic impact of AMR could be devastating. A recent study estimated that, by 2050, the annual cost of treating AMR could reach $100 trillion. That is more than the entire world economy today. 

The annual cost of treating MDR infections in the United States is estimated to be $20 billion. The economic impact of AMR is expected to rise in the coming years as the number of drug-resistant infections increases and more patients require treatment with expensive drugs. To reduce the toll of this growing problem, it is crucial to improve prescribing practices and increase public awareness about the importance of responsible antibiotic use. 

 

A Lack of Drug Development

The problem is compounded by the fact that few new antibiotics are being developed. In recent years, there has been a marked decrease in the number of antibiotics developed by pharmaceutical companies. This trend is cause for concern, as it threatens to leave us without effective treatments for bacterial infections. 

There are many reasons why fewer antibiotics are being developed today than in the past. One reason is that the market for new antibiotics is relatively small. Unlike other drugs, antibiotics are only used for a short period, so companies have a little financial incentive to invest in their development. 

In addition, the process of developing new antibiotics is costly and time-consuming, with a success rate of only about 1 in 10,000 molecules that are tested. As a result, many companies are focusing on other areas where they are more likely to see a return on their investment. Another reason for the decline in new antibiotic development is the increasing resistance of bacteria to existing drug treatments. As bacteria evolve, they become less susceptible to the effects of antibiotics. Even if a new antibiotic is developed, it may quickly become obsolete. 

In addition, many countries have strict regulations on the use of antibiotics, which limits their potential market. For these reasons, it is becoming increasingly difficult for pharmaceutical companies to justify the investment required to develop new antibiotics. As a result, the global impact of antimicrobial-resistant infections is significant and far-reaching. To put it simply, AMR is one of the most pressing challenges mankind has ever faced. And, with no easy solutions in sight, it is vital that we take action to reduce the spread of these dangerous infections. 

 

What Can We Do to Prevent or Combat This Resistance?

Antimicrobial resistance (AMR) is a major global health threat. Left unchecked, AMR could lead to 10 million deaths a year by 2050. So what can we do to prevent or combat this growing threat?

One way to combat AMR is to reduce the unnecessary use of antibiotics. Antibiotics should only be used to treat bacterial infections; they will not help to fight viral infections like colds and flu. In addition, it’s crucial to finish the entire course of antibiotics even if you’re feeling better, as stopping too early can allow bacteria to grow and develop resistance. Another way to reduce the spread of AMR is to practice good hygiene, such as washing your hands regularly and properly cooking food. 

As drug-resistant pathogens continue to evolve and spread, preventing and combating AMR becomes increasingly daunting. Nevertheless, we must take action to address this threat. To that end, efforts are underway to improve antimicrobial resistance surveillance, promote the prudent use of antibiotics, and develop new diagnostic tools and therapeutics. In addition, we must work to improve access to clean water, sanitation, and essential healthcare services worldwide. Only by addressing these challenges head-on will we be able to turn the tide against this growing public health threat.

 

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Author
Kimberly Hazel

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