What is antimicrobial resistance (AMR)?
Antimicrobial resistance occurs when a pathogen has developed a mechanism to render a therapeutic ineffective. Ineffective treatment can lead to complications/even death.
Why does it AMR matter?
The last 70-80 years have seen the introduction of many new classes of antimicrobials but also the emergence of resistance, in some cases immediately after introduction of the drugs. As a result, drug development is not keeping up with the pace of AMR and very few new classes of antimicrobials are in the development pipeline. We are in a POST ANTIBIOTIC ERA, where resistance is outpacing discovery of new antibiotics. The World Health Organization (W.H.O.) has determined AMR is a significant and emerging public health challenge, particularly as it is interspecies.
What is the mechanism for AMR?
The origin and spread of AMR occur when bacteria survive antimicrobials that are used against them, and some susceptible bacteria remain and grow due to natural selection leading to a genetic change. Additionally, 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 intrinsically resistant with a native defense mechanism. Typically, antibiotics are naturally produced by living organisms and bacteria sharing the same ecological niche have evolved mechanisms to withstand their effect making them intrinsically resistant. Some examples include reduced permeability of bacterial surfaces to drugs or efflux pumps that activity pump the drugs out of the cells. In some cases, some bacteria may lack features targeted by a particular antimicrobial drug and will become intrinsically resistant to that drug. For example, although many types of bacteria have cell walls, some like the mycoplasmas do not [2]. An antibiotic like penicillin that prevents cell-wall building can’t 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 clinical settings. Bacteria can acquire resistance in two ways: either through a new genetic change like mutations when exposed to an antibiotic that helps the bacterium survive, or by getting foreign DNA from a bacterium that is already resistant.
Genetic change
So how can a simple DNA change protect bacteria from antibiotics? Remember, DNA provides instructions to make proteins, so a change in DNA can cause a change in a protein. Sometimes this DNA change will affect the protein’s shape. If this happens at the place on the protein where an antibiotic acts, the antibiotic may no longer be able to recognize where it needs to do its job.
Changes like this can also prevent an antibiotic from getting into the cell or prevent the antibiotic from working once it’s inside. Once a change occurs, it can spread in a population of bacteria through replication and horizontal transfer or vertically by DNA transfer to other bacteria.
How do you find resistance markers?
Recent advances in genetics have allowed scientists to investigate features in drug resistant bacteria and identify those changes/genes that contributed to AMR phenotype. Thousands of such AMR markers found by genetic sequencing technologies and linked to AMR has been identified and recorded in national databases.
How does knowing about these markers help a doctor or veterinarian?
Until recently doctors or veterinarians didn’t really need to know about AMR markers. Antibiotics were readily available, there appeared to be frequent introduction of new drugs into the market when a previous generation had failed. However, prompted by a growing crisis of infections caused by drug resistant bacteria, new molecular technologies have evolved focusing on detection of genetic sequences that confer antimicrobial resistance. These technologies work by correlating the detection of an AMR marker to a resistance phenotype
Diagnostic and antimicrobial stewardships
The Centers for Disease Control, the Food & Drug Association, the American Veterinary Medical Association (AVMA), and other national and international agencies are urging physicians and veterinarians to practice diagnostic and antibiotic stewardships.
The concept of diagnostic stewardship is a vital cog in AMR surveillance and control activities in human clinical medicine. The W.H.O. defines diagnostic stewardship as “coordinated guidance and interventions to improve appropriate use of microbiological diagnostics to guide therapeutic decisions.” [3] The goal of diagnostic stewardship is to utilize the right test for the right patient to obtain accurate and clinically relevant results in a timely manner to deliver optimal care to the patient while conserving resources. Therefore, through the appropriate use of diagnostic tests, diagnostic stewardship guides patient management to optimize clinical outcomes and limit spread of antimicrobial resistance through judicious antimicrobial use.
The AVMA defines antimicrobial stewardship as the actions 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 safeguarding animal, public, and environmental health [4]. Antimicrobial stewardship involves maintaining animal health and welfare by implementing a variety of preventive and management strategies to prevent common diseases; using an evidence-based approach in making decisions to use antimicrobial drugs; and then using antimicrobials judiciously, sparingly, and with continual evaluation of the outcomes of therapy, respecting the client’s available resources.
How does it work in practice?
The gold standard for identifying an antimicrobial resistant infection for either human or animal patients requires growth of a suspected bacteria on an agar plate, followed by refined growth/culture in the presence of different concentrations of multiple antibiotics. After a period of three to five days, this technique can determine if a suspected bacterial infection is resistant to a particular antibiotic or not.
In practice a patient either must wait and suffer until the test results are available so that the correct antibiotic could be prescribed or receive an empirical prescription which may or may not be effective.
More recently polymerase chain reaction (PCR) technology is providing test results quickly, enabling faster diagnosis as well as the ability to practice antibiotic stewardship. While recently PCR has come to limelight as the most accurate test for diagnosis of COIVD-19, it’s ability as a molecular diagnostic tool is also powerful for diagnosis of other infectious diseases including detection of AMR genes.
An example of such technology is LexaGene’s MiQLab™ System. It is an automated PCR platform with integrated sample preparation and result reporting ideally suited to enable diagnostic stewardship at the veterinary point-of-care. The multiplexing capability of the MiQLab allows detection of multiple bacterial pathogens as well as AMR genes, providing actionable treatment decisions on tests done on appropriately collected samples from cats and dogs suspected of infections such as UTI, skin and soft tissue infections, wounds, and abscesses.
Summary
Recent adoption of PCR in clinical settings is enabling unparalleled ability to deliver high quality rapid molecular AMR test results days earlier than traditional phenotypic methods. Physicians and veterinarians can now confidently detect resistance markers and make evidence-based treatment decisions early in an infection to improve patient outcomes. Molecular diagnostic technologies are a step in the right direction of reducing the spread of AMR resistance, allowing scientists time to find the next class of antibiotics and use them judiciously.
LexaGene would like to recognize additional authors and editors for their contributions including but not limited to Diane Stewart, PhD.
Download our Antimicrobial Resistance Stewardship eBook to learn more.
