Antimicrobial resistance: the link between humans and animals

One Health is an approach that recognizes that the health of people is linked to the health of animals and our common environment

What is Antimicrobial Resistance (AMR)?

Antimicrobial resistance occurs when a pathogen has developed a mechanism to render a treatment ineffective. Ineffective treatment can lead to complications and even death.


Why is RAM important?

The last 70 to 80 years have seen the introduction of many new classes of antimicrobials but also the emergence of resistance, in some cases immediately after the introduction of drugs. As a result, drug development is not keeping pace with antimicrobial resistance and very few new classes of antimicrobials are being developed. We are in a POST-ANTIBIOTIC ERA, where resistance exceeds the discovery of new antibiotics. The World Health Organization (WHO) has identified antimicrobial resistance as an important and emerging public health challenge, especially since it is a cross-species problem.


What is the mechanism of RAM?

The origin and spread of AMR occurs when bacteria survive antimicrobials that are used against them, and some susceptible bacteria remain and grow due to natural selection resulting in genetic change. Also there are Markers, or genes, on bacterial DNA that provide unique defense strategies against distinct classes of antibiotics.


How do AMR markers work?[1]


Intrinsic resistance

In some cases, a type of bacteria will survive antibiotic treatment and multiply because it is inherently resistant with a native defense mechanism. Generally, antibiotics are naturally produced by living organisms and bacteria sharing the same ecological niche have developed mechanisms to resist their effect, which makes them inherently resistant. Some examples include reduced permeability of bacterial surfaces to drugs or efflux pumps that pump drugs out of cells. In some cases, certain bacteria may lack characteristics targeted by a particular antimicrobial drug and will become inherently resistant to that drug. For example, although many types of bacteria have cell walls, some like mycoplasma do not. [2]. An antibiotic like penicillin that prevents cell wall building cannot harm a bacterium that doesn’t build a cell wall in the first place.


Acquired Resistance

Bacteria can also acquire resistance and this form of resistance is much more important in the clinical setting. Bacteria can acquire resistance in two ways: either through a new genetic change such as mutations when exposed to an antibiotic that helps the bacterium survive, or by obtaining foreign DNA from an already resistant bacterium.


Genetic change

So how can a simple DNA change protect bacteria from antibiotics? Remember that DNA provides instructions for making proteins, so a change in DNA can lead to a change in a protein. Sometimes this DNA change will affect the shape of the protein. If this happens at the point in the protein where an antibiotic is working, the antibiotic may no longer be able to recognize where it needs to do its job.

Such changes can also prevent an antibiotic from entering the cell or prevent the antibiotic from working once it is inside. Once a change occurs, it can spread through a population of bacteria by replication and horizontal transfer or vertically by DNA transfer to other bacteria.


How do I find resistance markers?

Recent advances in genetics have allowed scientists to study the characteristics of drug-resistant bacteria and identify changes/genes that have contributed to the AMR phenotype. Thousands of these RAM markers found by genetic sequencing technologies and linked to RAM have been identified and registered in national databases.


How does knowing these markers help a doctor or veterinarian?

Until recently, doctors or veterinarians didn’t really need to know RAM markers. Antibiotics were readily available, there seemed to be a frequent introduction of new drugs to the market when an earlier generation had failed. However, prompted by a growing crisis of infections caused by drug-resistant bacteria, new molecular technologies have evolved focusing on the detection of genetic sequences that confer antimicrobial resistance. These technologies work by correlating the detection of an AMR marker to a resistance phenotype


Diagnostics and Antimicrobial Management

The Centers for Disease Control, Food & Drug Association, American Veterinary Medical Association (AVMA), and other national and international agencies urge physicians and veterinarians to practice diagnostic and antibiotic stewardship.

The notion of diagnostic stewardship is an essential cog in the surveillance and control activities of AMR in human clinical medicine. WHO defines diagnostic stewardship as “coordinated advice and interventions to improve the appropriate use of microbiological diagnostics to guide treatment decisions”. [3] The goal of diagnostic management is to use the right test for the right patient to obtain accurate and clinically relevant results in a timely manner to provide optimal patient care while conserving resources. Therefore, through the appropriate use of diagnostic tests, diagnostic management guides patient management to optimize clinical outcomes and limit the spread of disease. antimicrobial resistance through judicious use of antimicrobials.

The AVMA defines antimicrobial stewardship such as the steps that veterinarians take individually and as a profession to preserve the effectiveness and availability of antimicrobial drugs through conscientious oversight and responsible medical decision-making while protecting animal, public, and environmental health [4]. Responsible antimicrobial stewardship involves maintaining animal health and welfare by implementing a variety of prevention and management strategies to prevent common diseases; use an evidence-based approach to make decisions about the use of antimicrobial drugs; then using antimicrobials judiciously, sparingly, and with ongoing evaluation of treatment outcomes, respecting the client’s available resources.


How does it work in practice?

The gold standard for identifying antimicrobial resistant infection in human or animal patients requires growth of a suspected bacterium on an agar plate, followed by refined growth/culture in the presence of varying concentrations of multiple antibiotics. After a period of three to five days, this technique can determine whether a suspected bacterial infection is resistant to a particular antibiotic or not.

In practice, a patient must either wait and suffer until the test results are available so that the correct antibiotic can be prescribed, or be given an empirical prescription which may or may not be effective.

More recently polymerase chain reaction (PCR) technology quickly provides test results, enabling faster diagnosis as well as the ability to practice antibiotic management. While recently PCR has become the most accurate test for the diagnosis of COIVD-19, its ability as a molecular diagnostics tool is also powerful for the diagnosis of other infectious diseases, including the detection of AMR genes.

An example of such technology is LexaGene MiQLab™ System. It is an automated PCR platform with integrated sample preparation and results reporting, ideal for enabling diagnostic management at the veterinary point of care. The multiplexing capability of MiQLab enables the detection of multiple bacterial pathogens as well as AMR genes, providing actionable treatment decisions on tests performed on properly collected specimens from cats and dogs suspected of infections such as UTIs, skin and soft tissue infections, wounds and abscesses .


Summary

The recent adoption of PCR in clinical settings enables an unparalleled ability to deliver high-quality rapid molecular antimicrobial resistance test results days earlier than traditional phenotypic methods. Physicians and veterinarians can now confidently detect resistance markers and evidence-based treatment decisions early in an infection to improve patient outcomes. Molecular diagnostic technologies are a step in the right direction to reduce the spread of antimicrobial resistance, giving scientists time to find the next class of antibiotics and use them wisely.

LexaGene would like to thank other authors and editors for their contributions, including, but not limited to, Diane Stewart, PhD.

Download our Antimicrobial Resistance Management eBook to learn more.