by Tasha Phillips, M.S.
What is Antibiotic Resistance?
Antibiotic resistance, also known as antimicrobial resistance (AMR), is a major threat to both human and animal healthcare. According to a report from the Centers for Disease Control (CDC), antibiotic resistance causes approximately 2 million infections and 23,000 deaths every year in the United States alone.
As one of the most medically developed countries in the world, current antibiotics aren’t as effective against common pathogens seen in hospitals and clinics everywhere. Why are common bacteria becoming increasingly resistant to well-known antibiotics that are thought to be staples in our medicinal tool bag?
Another CDC report released in 2019 contains the current most serious bacterial threats and outline specific species that may become a more grim threat in the future. In this report, we see species such as carbapenem-resistant Acinetobacter, drug-resistant Candida auris, and multi-drug-resistant Pseudomonas aeruginosa.
Computer-generated image of Escherichia coli (E. coli), photo via the CDC
These strains alone caused between 8,500 and 32,600 cases of infection in 2017 respectively. Of those mentioned, some Acinetobacter species are resistant to nearly all antibiotics, including those used as a last resort effort like carbapenems. This gram-negative bacterium primarily causes pneumonia or infections of the blood stream.
When patients acquire resistant infections that require multi-modal care, second- and third-line defense antibiotics can cause serious side effects and damage to the patient. This is especially true for patients who receive organ transplants or chemotherapy that already have weakened immune defenses. In some cases, these infections cannot be treated at all.
If our current medications and treatments become ineffective against these serious pathogens, we have lost the ability to treat patients who otherwise would have survived. Pathogens that have developed multi-drug resistance often become resistant to chemotherapeutic agents as well.
AMR poses a real threat to veterinary medicine as well. The use of antibiotics in healthy animals used for food drives resistance further, and some resistant strains can then be transmitted to the human population.
Computer-generated image of Streptococcus pnuemoniae, bacteria that cause Strep Throat, photo via the CDC
Medical care of animals has progressed rapidly over the last 50 years. Specialist centers for neurology, internal medicine, and emergency medicine are popping up all across the country. Because human and animal populations are so intertwined, it's no surprise that we share some of the same pathogens and diseases.
The One Health Initiative was created to unite human and veterinary medicine by promoting and improving the well-being of all species. This collaboration between physicians, veterinarians, and other scientific health professionals intends to improve many aspects of healthcare including antimicrobial resistance.
Electron microscope image of Coxiella burnetii, bacteria that causes Q fever, photo via the CDC
Where and How Does Antimicrobial Resistance Begin?
Antimicrobial resistance is a naturally occurring process of evolution. As genetic sequences are altered through nucleotide mismatches, conjugation, transformation, or transduction, they may gain the genetic code for a particular resistance mechanism. This happens slowly as species evolve.
If a bacterium contains this resistance, it then shares it with its “offspring” and surrounding cells through different pathways. However, when antibiotics are used (especially in sublethal doses), this puts selective pressure on bacteria that contain those genes.
The ones that are strong enough to survive ensure those genetic codes are passed along. Before you know, a whole population of cells contains resistance genes, and the antibiotic is no longer effective against it.
If that’s the case, why are some common antibiotics still effective? Although antibiotics are putting pressure on these species to survive, it is still a slow process by our standards. As resistance evolves, bacteria can alter their pathways to “by-pass” the specific pathway that the drug alters or stops.
Common Resistance Mechanisms
When bacterial species have the genetic code and acquired some forms of resistance, how do they use it? There are several mechanisms and tactics bacteria use to evade death, but we will cover a few below.
Diagram of different antibiotic resistance mechanisms, sourced from Resistance Mechanisms article, via the ReAct Group
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Limiting Uptake
Some pathogens can limit the ability of a drug through preventing its penetration inside the cell. If the drug depends on extracellular binding, those sites can be altered to deny the drug access to the cell. If the drug can’t get in, it’s game over.
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Increasing Efflux Pumps
In cases where the drug does gain access inside the bacteria, the chemical signals inside the cell will increase the action of efflux pumps. These pumps will remove intracellular components that are not “self,” thereby removing the drug. So even though the drug has come inside, it's shipped directly back out.
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Chemical Structure Alterations
I mentioned that the binding sites of drugs can be changed to deny access. Another tactic is to change the structure of the antibiotic all together. This can be achieved through cleaving certain sites on the structure or by adding additional bonds where they don’t belong. The structure of the drug is highly important to remain active. If primary parts of the structure are changed – game over again.
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Hide and Seek (Biofilms)
The last mechanism we’ll cover is biofilms. Biofilms are used by over 500 species of bacteria, and they can either be created by a single species or a multispecies community. The bacteria secrete a layer of extracellular matrix, including proteins and sugars, that coat the top of the bacteria. This coating “force field” protects and hides the bacteria - not only from antimicrobials, but also from the host’s own immune defenses. The immune system may not always detect the infection brewing, nor can it penetrate through that outer layer to remove the bacteria. You can learn MUCH more about these nasty “germ fortresses” in our Biofilms post.
How Can We Help?
Worldwide antibiotic resistance seems like an impossible problem to tackle. The CDC and World Health Organization (WHO) have outlined ways in which healthcare professionals - as well as those who work outside the field - can help slow and correct some of the resistance we are seeing today.
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Use proper hygiene to control the spread of bacteria, including handwashing and food sanitization.
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When prescribed antibiotics, use them correctly and to completion to ensure the infection is cleared. Yes, take all of it and don’t “save some for later.”
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Clinicians: only prescribe antibiotics when necessary and avoid over-prescribing.
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Get bacterial cultures when available to ensure the correct drug is being used to clear infection the first go-around.
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Do not use antibiotics to prevent health issues in food animals (pork, poultry, cattle, etc.), and only use them under veterinary supervision.
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Continue to improve animal husbandry protocols to control illness and infection.
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Vaccinate domestic companion animals and food animals to control disease and illness.
How Can Lavengel Help with Antibiotic Resistance?
Microbiologists continue to study resistant strains to understand the mechanisms they use and find novel ways to combat them. Novel drugs are created to attack bacteria through different mechanisms that are safe for humans and animals.
This is where Lavengel comes in – even though it isn’t a “drug.” Because of Lavengel’s make-up, it is both hydrophobic and hydrophilic. That means it can cross lipid bilayers easily to penetrate deep into the skin and treat common wound infections.
Once it encounters bacterial cells, it can penetrate the cell wall and allow antioxidants to flush the intracellular space. This creates a double attack on the cell. Not only is the cell wall damaged, but the internal functioning of the bacteria is compromised.
Seeing Lavengel in action is something I have seen for myself as part of my own academic research. Current research is on-going to determine exactly what pathways are inhibited or destroyed by Lavengel inside different strains of bacteria.
On top of that, it is completely natural AND safe for pets (or you) to ingest if they lick the affected area. It’s been shown that Lavengel is effective against a variety of pathogens known to have resistant forms, including Staphylococcus bacteria.
Continuing to improve therapeutic treatments for resistant infections is paramount to ensuring public health, and Lavengel is one more step in the right direction - especially for our furry friends!
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Thanks for tuning in. If you’re curious about the One Health Initiative, check out their website that outlines their mission, goals, and lots of nerdy information about how our healthcare is connected.
Tasha Nelson Phillips is a veterinary assistant and researcher. She began her work in veterinary medicine in 2014 at a small practice in East Tennessee. She has a B.S. in Biology as well as a Master’s degree in Microbiology from East Tennessee State University. Her undergraduate and graduate research focused on Lavengel®, exploring its efficacy and mechanism of action against common bacterial species.
Tasha’s interests focus on natural antimicrobial options and exploring novel compounds to combat antibiotic resistance. She continues to work in small animal emergency and critical care medicine. She spends her free time with her husband and three furry babies in their East Tennessee home.