Health

C. difficile: A Fickle Foe

C. difficile infection is sometimes a tricky illness to treat because it is treated with antibiotics, which can further upset the gut flora.

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By: Liz Brown | October 10, 2013

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you're listening to an article from horse canada.com. c. difficile: a fickle foe by: liz brown. diarrhea. it’s the butt (excuse the pun) of juvenile jokes and camp songs. humour aside, though, in horses and humans it can be a condition that leads to severe dehydration and potential life-threatening situations if it isn’t monitored and its cause isn’t diagnosed and treated. in horses, there can be any number of culprits behind a bout of diarrhea – more medically referred to as colitis (inflammation of the colon). one of the more common causes, especially in equine hospitals, is the bacterium clostridium difficile, or c. difficile. horses affected with c. difficile can present with clinical signs ranging from mild to severe diarrhea, resulting in dehydration and toxemia that can lead to death. what is c. difficile? c. difficile is an anaerobic bacterium, meaning it lives in places where there is no oxygen and when it is exposed to the air, it dies. it lives in the gastrointestinal tract of many different animals, including both humans and horses. in the gut, it produces spores (dormant, highly resistant cells which can survive in unfavourable conditions then go on to reproduce) that are passed to the outside environment through feces. these spores are then picked up by horses through normal activities such as grazing and passed into the gastrointestinal tract, where they turn into active forms of the bacteria. there are pathogenic and non-pathogenic strains of c. difficile. this means some bacteria have the capacity to produce toxins that can cause illness, while some don’t. these toxins are known as toxin a and toxin b. advertisement scroll to continue with content interestingly, some horses can test positive for a pathogenic strain of c. difficile, but not show any signs of illness. “the numbers are variable, but three to five per cent of any population that is sampled will test positive for pathogenic strains of c. difficile, in some areas that can be even higher, up to seven or eight per cent,” said dr. luis arroyo, assistant professor of large animal medicine at the university of guelph, who studies equine and bovine gastroenterology and c. difficile-associated diarrhea. horses affected by c. difficile will present with diarrhea, sometimes a loss of appetite and sometimes a fever. in the most severe cases, the toxins can become so prolific in the colon that they cause tissue death and can eventually kill the horse. causes of c. difficile-associated diarrhea. although veterinarians and researchers cannot say with 100 per cent certainty why some horses become ill from the pathogenic strains of the bacteria and others do not, the generally accepted belief is that c. difficile causes illness when the normal flora of the gastrointestinal tract gets disrupted. this allows the pathogenic strains to begin multiplying in the gut, which produce toxins and cause the condition. in humans, c. difficile-associated diarrhea is linked to antibiotic use, as antibiotics can affect the bacteria makeup of the gastrointestinal tract. “in horses, we don’t know the real factors, but it’s probably something similar to humans,” said dr. arroyo. as such, horses given antibiotics that can disrupt normal gut flora are susceptible to a c. difficile infection. there also seems to be an acquired immunity to the bacteria, where those who have encountered it before are less likely to get sick from exposure to it. “in people, where most of the research has been done, it seems that if they’ve already been exposed to c. difficile, they might have a decreased risk of getting the disease,” said dr. j. trenton mcclure, professor of large animal medicine at the atlantic veterinary college, who recently completed a diagnostic study of c. difficile. in people, c. difficile seems to cause the most problems in the elderly and immune-compromised. “in humans, it’s mainly seen as a hospital-acquired disease. in horses, it’s a little less clear. while definitely some hospitals have a fair bit of c. difficile, others don’t,” added dr. mcclure. diagnosis. there are a few different lab methods used to detect the presence of c. difficile in horses. one method is to detect antigens to c. difficile toxins in feces, using an elisa enzyme-linked immunosorbent assay) test. this test is done in a lab with as little as one gram of fecal matter. the feces should be kept cool on ice packs while it is shipped to the lab, to ensure the toxins stay stable in the sample and a false negative result isn’t produced. another option is a bacterial culture, but a bacterial culture of c. difficile can be misleading because, as noted previously, some strains of c. difficile do not produce toxins that cause disease. one of the most time-efficient methods for c. difficile testing is through a real-time pcr (polymerase chain reaction) test. this test detects genetic material from c. difficile in the feces. but while these tests may demonstrate that there are toxigenic strains of c. difficile present in a horse’s feces, it doesn’t necessarily mean the c. difficile is the cause of the horse’s diarrhea. “we tend to think that if we detect a pathogenic strain and diarrhea is present that it’s the cause of the disease, but that’s not necessarily the case,” said dr. mcclure. in addition to running tests for c. difficile, veterinarians will also rule out other illnesses that can cause diarrhea, such as salmonella and potomac horse fever. during a study at the avc, dr. mcclure found that 14 per cent of horses admitted to the hospital (not presenting with diarrhea) were culture positive for c. difficile. “in a large percentage of horses, we don’tknow exactly the cause of the diarrhea,” added dr. arroyo. in some cases, however, veterinarians can be quite confident of the diagnosis. “in a horse that has clinical disease and toxins are found in large amounts in diarrheic samples using an elisa test (marketed for humans), it’s considered diagnostic,” he said. treatment and prevention. c. difficile infection is sometimes a tricky illness to treat because, somewhat ironically, it is treated with antibiotics, which can further upset the gut flora. some veterinarians will only treat serious cases of c. difficile with antibiotics. “in my opinion, if a horse is passing diarrhea, but he’s still eating and bright, antibiotics may not be required, even if he is diagnosed as a c. difficile positive case,” said dr. arroyo. in humans, the antibiotics typically used to treat c. difficile are metronidazole and vancomycin – antibiotics specifically targeted for anaerobic bacteria. metronidazole is the most common drug prescribed to treat c. difficile infection in horses. “there are occasionally resistant strains that have been reported and vancomycin is used in those instances. it isn’t typically recommended as a first-line drug and is only used in special cases,” said dr. mcclure, adding “vancomycin should not be used unless there is evidence of resistance to metronidazole.” both dr. mcclure and dr. arroyo note that reported cases of antibiotic-resistant strains of c. difficile are quite rare, though. in humans, fecal transplants are gaining momentum as a therapy for people who have c. difficile infections that antibiotics are unable to clear. a fecal transplant is exactly what it sounds like – taking one healthy person’s fecal material and transplanting it into the sick person’s colon via a nasogastric tube or enema. the introduction of “healthy” fecal matter promotes the regrowth of good bacteria in the colon, essentially “fixing” the bacterial imbalance. while the treatment method doesn’t sound too appealing, the success rate for this therapy is around 90 per cent. in the horse world, there are reports of foals suffering from diarrhea being cured by ingesting the manure of healthy adult horses. and an old horsemen’s tale for curing colic and diarrhea in horses is to concoct a “poo tea” – a brew of a healthy horse’s manure diluted in water, which and is administered orally to the sick horse. there are no science-based studies to back up this treatment, although it runs along the same idea as a fecal transplant. in the last few years, c. difficile has been increasing in virulence, which means that some strains of the bacteria proliferate at a higher rate than normal. “these strains are very efficient at producing toxins, especially when they are exposed to certain families of antibiotics,” said dr. arroyo. dr. arroyo points to a study performed in sweden a few years ago where they cultured a strain of c. difficile and harvested the spores. the spores were mixed with horse feces, which were left exposed to the environment in a fenced yard. five years later they were still able to culture c. difficile from the same sample. “some strains can live in the environment for a long time and be resistant to disinfectants and cleaning products,” he added. because c. difficile infection is spread by the ingestion of the bacteria’s spores that are present in the environment, one of the best methods of prevention is through good hygiene practices. the most important, and often overlooked, step in prevention is basic cleaning. “people tend to focus too much on the disinfectants, but it’s really making sure you get all the organic material and fecal matter completely out of the area by cleaning with soapy water and rinsing well with water,” said dr. mcclure. “the solution to pollution is dilution. if you don’t do adequate cleaning prior to disinfecting, the disinfecting isn’t nearly as effective.”. disinfecting c. difficile from surfaces isn’t as easy as killing other sorts of bacteria. “most disinfectants aren’t as effective against spores as they are against other types of bacteria,” said dr. mcclure. he noted that household bleach is effective in high concentrations (diluted in water at a 1:10 ratio), but the most effective disinfectant to use is probably an accelerated hydrogen peroxide such as virox (diluted in water at a 1:16 part ratio). another important consideration is that c. difficile can also cross-infect humans, so when dealing with a sick horse, it’s essential for caregivers to maintain good hygiene practices as well. “frequent hand washing is always a good idea and in a hospital setting we would wear protective gowning,” said dr. arroyo. “it’s a non-selective organism that can affect animals across species and most likely there will be some degree of crossover.”. ongoing research. in canada, there is much ongoing research into c. difficile. currently dr. emma allen-vercoe at the university of guelph and her clinical colleague dr. elaine petrof at queen’s university are trying to develop a safer and less unpleasant treatment alternative to fecal transplant for humans. they have created a synthetic probiotic they’ve called repoopulate, which they’ve administered to test patients via colonoscopy with successful results. eventually, they hope this sort of probiotic could be developed into an oral preparation in a pill form. “it would be very feasible (given the money, time and resources) to create a similar super-probiotic preparation derived from a healthy donor horse for use in treating these animals,” said dr. allen-vercoe. also at the university of guelph, dr. scott weese is examining the presence of c. difficile in meat and the prevalence of the bacteria in different animals, from cattle to chickens. dr. arroyo is involved in ongoing c. difficile research looking at the bacteria as the potential cause of proximal enteritis (an inflammation of the first section of the small intestine that causes serious colic). ‘we have found that most horses with proximal enteritis will test positive for c. difficile in the stomach fluids, so we are conducting further studies to see if there is a real link,’ he said. at the avc, dr. mcclure is preparing to publish a study he has completed on risk factors for horses being carriers of c. difficile. in his study, his team tested horses (who showed no c. difficile infection symptoms) admitted to the hospital. they found that stallions were most likely to be carriers of c. difficile, while geldings were least likely, with mares falling in between. while the team’s first thought was that breeding operations or racetracks might be the places where the horses were picking up this bacterium, because these are the areas where intact males are most likely to reside. “when we did further analysis, neither of these (racetracks or breeding operations) came out as significant, so it’s hard to say (if there is a correlation) with our study,” said dr. mcclure. conclusion. c. difficile is a non-selective bacteria that can infect a wide range of animals, from horses to humans and even elephants. while in humans the bacteria and how it causes disease is better understood, there is much to still be learned on its effects in horses. “in a large percentage of horses we don’t know the cause for diarrhea,” reiterated dr. arroyo. and when this is the case, often the best course of action is supportive care to minimize dehydration and close observation of the horse’s condition to ensure it doesn’t deteriorate. &&>

Diarrhea. It’s the butt (excuse the pun) of juvenile jokes and camp songs. Humour aside, though, in horses and humans it can be a condition that leads to severe dehydration and potential life-threatening situations if it isn’t monitored and its cause isn’t diagnosed and treated. In horses, there can be any number of culprits behind a bout of diarrhea – more medically referred to as colitis (inflammation of the colon). One of the more common causes, especially in equine hospitals, is the bacterium Clostridium difficile, or C. difficile. Horses affected with C. difficile can present with clinical signs ranging from mild to severe diarrhea, resulting in dehydration and toxemia that can lead to death.

What is C. difficile?

C. difficile is an anaerobic bacterium, meaning it lives in places where there is no oxygen and when it is exposed to the air, it dies. It lives in the gastrointestinal tract of many different animals, including both humans and horses. In the gut, it produces spores (dormant, highly resistant cells which can survive in unfavourable conditions then go on to reproduce) that are passed to the outside environment through feces. These spores are then picked up by horses through normal activities such as grazing and passed into the gastrointestinal tract, where they turn into active forms of the bacteria.

There are pathogenic and non-pathogenic strains of C. difficile. This means some bacteria have the capacity to produce toxins that can cause illness, while some don’t. These toxins are known as Toxin A and Toxin B.

Scroll to continue with content

Interestingly, some horses can test positive for a pathogenic strain of C. difficile, but not show any signs of illness. “The numbers are variable, but three to five per cent of any population that is sampled will test positive for pathogenic strains of C. difficile, in some areas that can be even higher, up to seven or eight per cent,” said Dr. Luis Arroyo, Assistant Professor of Large Animal Medicine at the University of Guelph, who studies equine and bovine gastroenterology and C. difficile-associated diarrhea.

Horses affected by C. difficile will present with diarrhea, sometimes a loss of appetite and sometimes a fever. In the most severe cases, the toxins can become so prolific in the colon that they cause tissue death and can eventually kill the horse.

Causes of C. difficile-associated Diarrhea

Although veterinarians and researchers cannot say with 100 per cent certainty why some horses become ill from the pathogenic strains of the bacteria and others do not, the generally accepted belief is that C. difficile causes illness when the normal flora of the gastrointestinal tract gets disrupted. This allows the pathogenic strains to begin multiplying in the gut, which produce toxins and cause the condition.

In humans, C. difficile-associated diarrhea is linked to antibiotic use, as antibiotics can affect the bacteria makeup of the gastrointestinal tract. “In horses, we don’t know the real factors, but it’s probably something similar to humans,” said Dr. Arroyo. As such, horses given antibiotics that can disrupt normal gut flora are susceptible to a C. difficile infection.

There also seems to be an acquired immunity to the bacteria, where those who have encountered it before are less likely to get sick from exposure to it. “In people, where most of the research has been done, it seems that if they’ve already been exposed to C. difficile, they might have a decreased risk of getting the disease,” said Dr. J. Trenton McClure, professor of large animal medicine at the Atlantic Veterinary College, who recently completed a diagnostic study of C. difficile.

In people, C. difficile seems to cause the most problems in the elderly and immune-compromised. “In humans, it’s mainly seen as a hospital-acquired disease. In horses, it’s a little less clear. While definitely some hospitals have a fair bit of C. difficile, others don’t,” added Dr. McClure.

Diagnosis

There are a few different lab methods used to detect the presence of C. difficile in horses. One method is to detect antigens to C. difficile toxins in feces, using an ELISA enzyme-linked immunosorbent assay) test. This test is done in a lab with as little as one gram of fecal matter. The feces should be kept cool on ice packs while it is shipped to the lab, to ensure the toxins stay stable in the sample and a false negative result isn’t produced.

Another option is a bacterial culture, but a bacterial culture of C. difficile can be misleading because, as noted previously, some strains of C. difficile do not produce toxins that cause disease.

One of the most time-efficient methods for C. difficile testing is through a real-time PCR (polymerase chain reaction) test. This test detects genetic material from C. difficile in the feces.

But while these tests may demonstrate that there are toxigenic strains of C. difficile present in a horse’s feces, it doesn’t necessarily mean the C. difficile is the cause of the horse’s diarrhea. “We tend to think that if we detect a pathogenic strain and diarrhea is present that it’s the cause of the disease, but that’s not necessarily the case,” said Dr. McClure.

In addition to running tests for C. difficile, veterinarians will also rule out other illnesses that can cause diarrhea, such as Salmonella and Potomac Horse Fever.

During a study at the AVC, Dr. McClure found that 14 per cent of horses admitted to the hospital (not presenting with diarrhea) were culture positive for C. difficile.

“In a large percentage of horses, we don’tknow exactly the cause of the diarrhea,” added Dr. Arroyo. In some cases, however, veterinarians can be quite confident of the diagnosis. “In a horse that has clinical disease and toxins are found in large amounts in diarrheic samples using an ELISA test (marketed for humans), it’s considered diagnostic,” he said.

Treatment and Prevention

C. difficile infection is sometimes a tricky illness to treat because, somewhat ironically, it is treated with antibiotics, which can further upset the gut flora. Some veterinarians will only treat serious cases of C. difficile with antibiotics. “In my opinion, if a horse is passing diarrhea, but he’s still eating and bright, antibiotics may not be required, even if he is diagnosed as a C. difficile positive case,” said Dr. Arroyo.

In humans, the antibiotics typically used to treat C. difficile are metronidazole and vancomycin – antibiotics specifically targeted for anaerobic bacteria. Metronidazole is the most common drug prescribed to treat C. difficile infection in horses. “There are occasionally resistant strains that have been reported and vancomycin is used in those instances. It isn’t typically recommended as a first-line drug and is only used in special cases,” said Dr. McClure, adding “vancomycin should not be used unless there is evidence of resistance to metronidazole.” Both Dr. McClure and Dr. Arroyo note that reported cases of antibiotic-resistant strains of C. difficile are quite rare, though.

In humans, fecal transplants are gaining momentum as a therapy for people who have C. difficile infections that antibiotics are unable to clear. A fecal transplant is exactly what it sounds like – taking one healthy person’s fecal material and transplanting it into the sick person’s colon via a nasogastric tube or enema. The introduction of “healthy” fecal matter promotes the regrowth of good bacteria in the colon, essentially “fixing” the bacterial imbalance. While the treatment method doesn’t sound too appealing, the success rate for this therapy is around 90 per cent.

In the horse world, there are reports of foals suffering from diarrhea being cured by ingesting the manure of healthy adult horses. And an old horsemen’s tale for curing colic and diarrhea in horses is to concoct a “poo tea” – a brew of a healthy horse’s manure diluted in water, which and is administered orally to the sick horse. There are no science-based studies to back up this treatment, although it runs along the same idea as a fecal transplant.

In the last few years, C. difficile has been increasing in virulence, which means that some strains of the bacteria proliferate at a higher rate than normal. “These strains are very efficient at producing toxins, especially when they are exposed to certain families of antibiotics,” said Dr. Arroyo.

Dr. Arroyo points to a study performed in Sweden a few years ago where they cultured a strain of C. difficile and harvested the spores. The spores were mixed with horse feces, which were left exposed to the environment in a fenced yard. Five years later they were still able to culture C. difficile from the same sample. “Some strains can live in the environment for a long time and be resistant to disinfectants and cleaning products,” he added.

Because C. difficile infection is spread by the ingestion of the bacteria’s spores that are present in the environment, one of the best methods of prevention is through good hygiene practices. The most important, and often overlooked, step in prevention is basic cleaning. “People tend to focus too much on the disinfectants, but it’s really making sure you get all the organic material and fecal matter completely out of the area by cleaning with soapy water and rinsing well with water,” said Dr. McClure. “The solution to pollution is dilution. If you don’t do adequate cleaning prior to disinfecting, the disinfecting isn’t nearly as effective.”

Disinfecting C. difficile from surfaces isn’t as easy as killing other sorts of bacteria. “Most disinfectants aren’t as effective against spores as they are against other types of bacteria,” said Dr. McClure. He noted that household bleach is effective in high concentrations (diluted in water at a 1:10 ratio), but the most effective disinfectant to use is probably an accelerated hydrogen peroxide such as Virox (diluted in water at a 1:16 part ratio).

Another important consideration is that C. difficile can also cross-infect humans, so when dealing with a sick horse, it’s essential for caregivers to maintain good hygiene practices as well. “Frequent hand washing is always a good idea and in a hospital setting we would wear protective gowning,” said Dr. Arroyo. “It’s a non-selective organism that can affect animals across species and most likely there will be some degree of crossover.”

Ongoing Research

In Canada, there is much ongoing research into C. difficile. Currently Dr. Emma Allen-Vercoe at the University of Guelph and her clinical colleague Dr. Elaine Petrof at Queen’s University are trying to develop a safer and less unpleasant treatment alternative to fecal transplant for humans. They have created a synthetic probiotic they’ve called RePOOPulate, which they’ve administered to test patients via colonoscopy with successful results. Eventually, they hope this sort of probiotic could be developed into an oral preparation in a pill form. “It would be very feasible (given the money, time and resources) to create a similar super-probiotic preparation derived from a healthy donor horse for use in treating these animals,” said Dr. Allen-Vercoe.

Also at the University of Guelph, Dr. Scott Weese is examining the presence of C. difficile in meat and the prevalence of the bacteria in different animals, from cattle to chickens.

Dr. Arroyo is involved in ongoing C. difficile research looking at the bacteria as the potential cause of proximal enteritis (an inflammation of the first section of the small intestine that causes serious colic). ‘We have found that most horses with proximal enteritis will test positive for C. difficile in the stomach fluids, so we are conducting further studies to see if there is a real link,’ he said.

At the AVC, Dr. McClure is preparing to publish a study he has completed on risk factors for horses being carriers of C. difficile. In his study, his team tested horses (who showed no C. difficile infection symptoms) admitted to the hospital. They found that stallions were most likely to be carriers of C. difficile, while geldings were least likely, with mares falling in between. While the team’s first thought was that breeding operations or racetracks might be the places where the horses were picking up this bacterium, because these are the areas where intact males are most likely to reside. “When we did further analysis, neither of these (racetracks or breeding operations) came out as significant, so it’s hard to say (if there is a correlation) with our study,” said Dr. McClure.

Conclusion

C. difficile is a non-selective bacteria that can infect a wide range of animals, from horses to humans and even elephants. While in humans the bacteria and how it causes disease is better understood, there is much to still be learned on its effects in horses. “In a large percentage of horses we don’t know the cause for diarrhea,” reiterated Dr. Arroyo.

And when this is the case, often the best course of action is supportive care to minimize dehydration and close observation of the horse’s condition to ensure it doesn’t deteriorate.