A wide variety of antibiotic drugs have saved millions of lives by killing the deadly bacteria that make people and animals sick. But, increasingly, bacteria are becoming resistant to the most-used antibimicrobial drugs. A bacterium is deemed to be resistant if it can survive in the highest concentration of the antibiotic drug that can be achieved in the animal’s body. We’ve known that this is true for humans for some time, but it is also true for horses.
What is Antibiotic Resistance?
When a horse has a bacterial infection, and is given an antibiotic drug, most of the targeted bacteria in the animal’s system will be killed. However, out of the millions of bacteria present in the sick animal’s body, some will have natural mutations that make them resistant to the drug, so they survive.
This resistance takes various forms. According to a 2012 article in the Equine Veterinary Journal by Dr. Thomas Maddox from the University of Liverpool, antibiotics work by interrupting certain metabolic functions in the bacterial cells. They may break down the cell walls, stop the bacteria from making DNA/RNA (which is necessary for the bacteria to reproduce), or prevent the bacteria from making the protein it needs. In a similar way, the resistant bacteria have four main paths to resistance: they protect or modify the part of the cell’s exterior where the antibiotics would normally attach; they make the cell walls less permeable so the antibiotics can’t get in; they produce enzymes to inactivate the antibiotics; or they pump out any antibiotics that penetrate the cell.
Bacteria reproduce rapidly and each reproductive cycle introduces the chance for mutations – and some of those mutations may make the bacterium resistant to a particular antibiotic drug. When the horse is treated with the drug, all the non-resistant bacteria will be killed, but the resistant ones will survive. That means those resistant ones are the only ones left to reproduce, and the next generation of bacteria will be composed almost entirely of resistant bacteria.
Continued exposure to the drug is a form of natural selection for resistance.
Exponential Spread
Researchers like Dr. Maddox have found that the development and spread of resistance is more complex, and worrying, than simple natural selection through mutations in the chromosomes would suggest. While bacteria reproduce by dividing – they don’t mate – they can transfer genetic material to each other through what are called “mobile genetic elements.” Mobile genetic elements are types of DNA that can move around within the genome and can include plasmids, gene cassettes linked to integrons, and transposons. Dr. Patrick Boerlin, a molecular epidemiologist at the University of Guelph, has been studying these in several different species of animals.
Dr. Boerlin explained, “Bacterium A might have a plasmid with the DNA coding to resist tetracycline, an antibiotic. Bacterium B does not, but A can pass on a plasmid with that code. Now B is also resistant to tetracycline. That means resistance can spread even faster than the bacteria can reproduce.”
These plasmids or other mobile genetic elements can carry resistance to more than one antibiotic as well. For example, that plasmid that encodes for resistance to tetracycline might also carry a gene for resistance to penicillin. The horse is treated with tetracycline, killing off the bacteria that are not resistant to that drug and increasing the percentage of tetracycline-resistant bacteria. But because the plasmid protecting the bacteria ALSO encoded resistance to penicillin, you have now also selected for penicillin resistance – even though you haven’t used penicillin at all.
And it gets even more nefarious. Both people and animals have millions of beneficial bacteria living in their bodies. They are, in fact, necessary to keep us healthy. But, just like the bacteria that make us sick, these good bacteria have plasmids and other mobile genetic elements. That means harmful bacteria can pass on the plasmids carrying antibiotic resistance to the good bacteria, that then form a reservoir of resistant genes that can subsequently be passed on to other unfriendly bacteria.
In some cases, the resistant bacteria can be passed on not just from one horse to another, but between animals of different species. Your horse that has never been treated with penicillin, for example, may pick up penicillin-resistant bacteria from cows kept on the same farm.
Identifying the Risks
In fact, contact with certain other types of animals is one of the factors identified by Dr. Maddox in his study entitled Cross-sectional study of antimicrobial-resistant bacteria in horses. Part 2: Risk factors for faecal carriage of antimicrobial-resistant Escherichia coli in horses. Part 1 of his study, which looked at 692 horses from 65 veterinary practices in the UK, found that almost 70 per cent of the horses tested had E. coli bacteria in their feces that were resistant to at least one antimicrobial drug.
For Part 2, Dr. Maddox wanted to do a more in-depth analysis and determine the factors that increased the risk of the horses having the resistant bacteria. He found that the significant ones were:
+ Recent hospitalization. A horse hospitalized in the past 10 days was 12 times as likely to have resistant E. coli bacteria in his system than one that had not been hospitalized. Three months after coming home from the hospital, that risk has dropped to about twice as high as one that was never in hospital.
+ Contact with certain animals (other than horses). Horses that had access to other farm animals such as cows, pigs, sheep and chickens were more than twice as likely to have resistant E. coli. Contact with wild animals also increased the risk.
+ The type of farm or stable where the horse was kept. Horses kept on a mixed farm were six times as likely to have resistant E.coli, compared to those kept on a horses-only premises where they were primarily in a field (the lowest rate). Horses on a breeding farm had double the risk. Riding schools and racing yards had lower rates, similar to the horse farms where the animals lived outdoors.
+ The surrounding land use. Horses kept in urban areas had more than three times the risk of harbouring resistant E. coli, while those who were stabled in an area surrounded by crop farms were more than double the risk, compared to those surrounded by grazing land.
+ Veterinary treatment in the previous six months. Any veterinary treatment increased the risk, but treatment for certain things (respiratory illness, gastrointestinal illness or a wound) increased it further. Dr. Maddox comments in the discussion of the study that it was surprising how long the effects of veterinary care – or, perhaps, the illness that required the care – continued to influence antimicrobial resistance.
+ Antimicrobial treatment in the previous 10 days. The most significant was treatment with the drug enrofloxacin, which increased the risk of resistant E. coli by 26 times! Most others led to three or four times the risk.
+ Being stabled near a horse who had been recently hospitalized. Horses that were stabled near and likely to have contact with a horse that had recently been hospitalized had about four times the risk of testing positive for resistant E. coli.
Seeing this data helps clarify the many ways in which resistant bacteria can be acquired. While Dr. Maddox and his co-researchers were not able in this study to determine exactly why these factors were important, it does highlight some steps that may reduce the risk.
Dr. Boerlin is also studying the ways that resistance is passed between animals of different species. He’s intrigued by the fact that some of the plasmids transfer readily between, for example, bacteria in cattle and bacteria in pigs while others don’t. “If we can discover why some don’t transfer, we may be able to figure out how to prevent that transfer happening in other situations,” he said.
Reducing the Risks
One of the most important strategies in preventing resistance is to use antibiotics cautiously. Dr. Maddox said “The overuse of antimicrobial drugs is one of the main drivers of resistance, and so limiting the use of these is clearly one of the most important things we can all do. In particular, their use when they are not really required – if there is no actual evidence that there is a bacterial infection – should be discouraged wherever possible.”
If a veterinarian is considering this type of treatment, testing the bacteria present in the horse’s system to determine the most appropriate antibiotic to use will not only reduce resistance, but produce the best clinical outcome for the horse as well.
Horse owners can also reduce the risks by avoiding or minimizing the risk factors identified in Dr. Maddox’s study.
He emphasized that the horses in his study were all healthy. “Many animal species carry a huge number of bacteria harmlessly. However, if the animal becomes susceptible in some way, for example if their immune system is suppressed by an illness or another factor, or if they have a wound, then it is possible for these previously harmless bacteria to be the cause of an infection.”
Taking good care of your horse in general will help keep his immune system strong so he’s less likely to become ill.
The Future of Resistance
What is the downside if antibiotic resistance is allowed to continue to spread? Between 1929 (when penicillin was discovered) and 1969, about 28 new types of antibiotics were discovered and put on the market. There was then a 40-year gap with no new treatments. Although four more antibiotics were developed in the late 2000s and early 2010s, these may not be enough to compensate for the problem of resistance.
Dr. Boerlin points to a February 2016 study from China (Liu YY, Wang Y et al), which showed some bacteria in a strain of E. coli had resistance to the polymyxin antibiotics, carried on plasmids. “This is yet another resistance we did not expect to show up,” he said. “It is targeting a last-resort antibiotic medicine we had to get out of the drawer because of all the other resistances.” He added that this polymyxin resistance has now been found in Canada.
As more bacteria develop resistance to the drugs already available, we see a huge growth in the risk of serious complications and even death from infections that were previously easily treated. And because of the ways that resistance can be passed from one bacterium to another, no species – including the human species – is safe. As Dr. Boerlin said, quoting his fellow researcher Dr. John Prescott, “Resistance anywhere is resistance everywhere.”
