Here's What You Should Know About Antibiotic Cross-Resistance and Co-Resistance

By Madeleine Kleven, FACT’s Safe and Healthy Food Program Coordinator

In the Safe and Healthy Food Program’s work we talk a lot about antibiotic resistance - when a bacterial organism can no longer be killed by the antibiotics normally used to treat that bacterial infection. On a big picture level, the overuse of antibiotics, especially in industrial farming is a main driver of antibiotic resistance. This is a big problem, especially for those antibiotics which are medically important - used in both animals and humans.

Let’s say a farm frequently uses fluoroquinolones (a class of antibiotics we’ll call “Florie” for short) to treat chickens for stomach issues caused by Salmonella, this will kill some of the bacteria, but the bacteria that are resistant to Florie will survive and replicate. As Florie is used more and more, the resistant colonies will grow larger and start to outnumber non-resistant bugs. Eventually the resistant bacteria (Salmonella) will be shed in chicken poop, which can spread to the environment or contaminate your food.

Now say a person gets infected with this bacteria from consuming contaminated meat. A doctor might normally prescribe Florie to treat their infection, but unfortunately the bacteria is resistant to Florie so the patient needs further treatment, a longer hospital stay, greater recovery, and often needs to pay a lot more money for being treated.

With medically important antibiotics, we can see a very clear connection between animal and human health -  antibiotic overuse in animals can lead to limited treatment options in humans. (Fun fact, because the efficacy of fluoroquinolones was being compromised by overuse in animal and human medicine, the FDA banned fluoroquinolone use in poultry in 2005 to make sure they can still be used to treat human infections.) In order to make sure other shared antibiotics stay effective, the FDA developed a list of medically important antibiotics - antibiotics on this list require a prescription from a veterinarian and they can’t be used to make animals grow faster. These limitations on how they can be used help keep them effective for both animals and people.

But what about non-medically important antibiotics? Do we need to worry about resistance to these too? In short, the answer is yes. Non medically important antibiotics are only used in animal medicine, they aren’t used to treat people, so it has been widely assumed that their use does not impact human health. However, that’s not the case. In fact, overusing an antibiotic whether it is medically important or not can actually promote the survival and growth of bacteria that are resistant to other antibiotics as well.

This happens through co-resistance and cross-resistance. How does this work? Let’s break it down.

Antibiotic Cross-Resistance:

Now, antibiotic cross-resistance happens when bacteria become resistant to one antibiotic, and as a result, they also become resistant to other antibiotics that belong to the same group or have a similar structure. It's like the bacteria develop a kind of superpower that helps them resist multiple types of antibiotics.

Let me give you an example to make it clearer. Imagine you have two wizard antibiotics who are siblings. Wizard A is really great at killing bacteria by casting a special spell. Wizard B is also good at killing bacteria by casting a slightly different spell. Now say the bacteria develops the ability to resist Wizard A’s spell. Because Wizard B uses similar magic, the bacteria to varying degrees are also able to resist the spell of Wizard B.

Cross-resistance most often happens when antibiotics are in the same class or work in similar ways. It can also happen to unrelated antibiotics as well through things like efflux pumps. Basically, the bacteria develops the ability to pump out foreign invaders, so regardless of how similar the antibiotics are, the bacteria spots them coming into the cell and pushes them back out.

An example of cross resistance is where the use of the drug bacitracin, which the FDA currently considers not important for human medicine can lead to resistance to the last resort drug colistin.

Antibiotic Co-Resistance:

Co-resistance happens when bacteria develop resistance to multiple antibiotics at the same time. This can occur because bacteria have the ability to share and exchange genetic material with each other, including the genes that give them resistance to antibiotics.

Imagine you have a group of bacteria, and each one of them has its own special set of defenses against different antibiotics. If these bacteria come into contact with each other, they can transfer their resistant genes to one another. This means that the bacteria that were previously susceptible to one antibiotic can become resistant to multiple antibiotics because they acquired the resistance genes from the other bacteria. These genes can all get attached to each other as a single multidrug resistance package.

The multidrug resistance package protects the bacteria from any of the multiple drugs and bacteria can then share the package with other bacteria. If a gene providing resistance to a drug that is not used in humans is packaged with a drug that is important for use in humans (e.g., fluoroquinolones) using the drug not important to human medicine may lead to the spread of resistance to the medically important one. Like we talked about above, if an antibiotic is being used frequently, then the bacteria that are resistant are at an advantage and they will keep replicating and surviving. For example, using the animal only drug narasin has been linked to resistance to vancomycin, a drug used to treat serious infection in people.

The widespread use of antibiotics in both human medicine and agriculture contributes to co-resistance. Antibiotics are used not only to treat infections but also for various other purposes, such as prevention and growth promotion in livestock. This extensive use provides more opportunities for bacteria to develop and exchange resistance genes, increasing the chances that a bacteria will become resistant to multiple antibiotics.

Antibiotic resistance is a complicated topic in general, without throwing cross and co-resistance into the mix. But as a main takeaway you should be aware that the overuse of antibiotics whether they are non-medically important or medically important can make human antibiotics less effective. When our antibiotics are less effective everyone suffers, especially those populations who need antibiotics the most. While there are some new antibiotics and drugs being developed, they’re not being developed near fast enough. A sure fire way to preserve our antibiotics for as long as we can, is to use them as judiciously as possible.