Case: Antibiotic-Induced Diarrhea

A three-year-old Standardbred gelding was presented to the hospital for evaluation and treatment of diarrhea (colitis). The previous week the horse had developed a mild hind-limb lameness which seemed to come and go, and it was decided to treat the horse with antibiotics “just in case” it had something to do with an infection. The horse was treated with ceftiofur (an antibiotic, often sold under the brand name Excenel or Naxcel) for five days. On the fifth day, the gelding developed moderate to severe diarrhea. The next morning the horse also had a fever. He was treated with anti-inflammatories and quickly referred to the hospital for intensive care.

On presentation, the gelding was very quiet. He had a very high heart rate, reddish gums and he was significantly dehydrated. Intestinal sounds could not be heard over the abdomen, indicating that the horse’s intestines were not moving normally, and there was a “ping” on the right side of the abdomen, indicating that there was gas accumulating in the cecum (part of the large intestine). Treatment with intravenous (IV) fluids was started right away to try to correct the dehydration and keep up with the amount of fluid the horse was losing in its diarrhea.

By the next morning the horse’s attitude was improved, but his gums were still an abnormal colour (“toxic mucous membranes”, see picture), indicating that there were inflammatory cytokines (substances released by cells when they’re in distress) and likely bacterial toxins in horse’s bloodstream. Also, despite the IV fluids, the gelding was still dehydrated, likely because he was pooling fluid from his body tissues in his intestine, as well as the more obvious loss of fluid in his ongoing diarrhea. This went on for another two days, despite intensive treatment in the hospital. On the fourth day, the gelding developed severe signs of colic. His large colon became progressively more distended with gas, and the contents of his small intestine started to back-up into his stomach. His heart rate became extremely high, and his pain could not be controlled with sedatives or anti-inflammatories. A belly-tap yielded a red-tinged fluid (normally belly fluid is light yellow), and the concern at that point was that the intestines had become twisted (which can happen in horses with diarrhea as a result of their abnormal intestinal motility). Despite the risks, it was decided to take the horse to surgery - but there was no twist in the bowel. The cause of the colic was that the large colon was severely distended with gas and fluid, and it was barely moving at all. The appearance of the large colon was consistent with extreme inflammation, and the tip of the cecum looked so bad that the surgeons decided to remove it because it was likely dead or dying.

The horse recovered from anesthesia, and IV fluid therapy was continued. Later that day, when the horse was offered some pellets, some intestinal sounds were detectable. The horse soon started to pass diarrhea again, but overall his attitude was much brighter, and his hydration status and (remarkably) blood protein levels remained stable.

Unfortunately the day after surgery the gelding became reluctant to move around the stall. Increased digital pulses were detected on the front feet, and the horse was sensitive to hoof testers – the gelding was developing laminitis. Despite additional treatment, the signs of laminitis became worse and worse. In the end the horse was euthanized, less than a week after being admitted to the hospital.

On necropsy, the entire large colon was severely thickened, filled with green-yellow fluid, and the mucosa (inside surface of the intestine) was ulcerated. Signs of severe acute laminitis were present in all four feet. A specific causative agent of the colitis could not be identified – tests for Salmonella and clostridial toxins were all negative. This is not too surprising as no agent is identified in over half of all adult horse colitis/diarrhea cases. But there is no doubt what set this terrible chain of events in motion – treatment with antibiotics, for a condition that may or may not have ever required antibiotic treatment in the first place.

We talk a lot about antibiotic-induced colitis/diarrhea in horses, but until you’ve seen it for yourself, it can be hard to believe that drugs used every day in both people and animals can have such a devastating effect on a horse. Antibiotics certainly do save lives, but unfortunately there are no “miracle cures” that are entirely without drawbacks. This case clearly demonstrates one of the most important reasons why we so strongly advocate prudent use of antibiotics in horses – their use should never be employed lightly. Although this is a “worst case scenario” that overall occurs uncommonly, the potential is there and should always be taken into consideration.

Photo credit: M. Anderson 2007

Bug of the Month: Rotavirus

Rotavirus is an important cause of diarrhea in young horses. (It's also a major cause of diarrhea in infants, but a different rotavirus is involved). Exposure to rotavirus is very common - most, if not all, horses are exposed to it early in life. Disease only occurs in foals, but not every foal that gets exposed becomes sick. Most often, rotavirus causes diarrhea if foals between 1 and 6 months of age, with most cases occurring between 1 and 3 months of age. Foals less than 1 month of age can be affected, but it's less common.

Foals become infected by swallowing the virus, which they usually pick up from the feces of other horses (including their mares) in their environment. The exact source of infection is rarely identified. It is likely that some healthy adult horses are the reservoirs and shed the virus in their manure.

Like other types of diarrhea, rotaviral diarrhea in foals can range from mild diarrhea alone to severe diarrhea with weakness, loss of appetite and dehydration. Colic can occur because of intestinal cramping associated with diarrhea. You cannot differentiate diarrhea due to rotavirus from other types of diarrhea by appearance alone. The diarrhea must be tested to identify the cause.

There is no specific treatment for rotavirus infection, but "supportive care" is often provided. One of the primary components of supportive care is fluid therapy, which may be needed for foals that start to become weak and dehydrated. Aggressive intravenous fluid therapy may be needed in some cases, depending on the severity.

Rotavirus vaccines are available in some regions, although there is limited evidence that they have much of an effect. Few people recommend vaccination. Rather, good attention to foal management practices, hygiene and early diagnosis of infected foals is the key. Foaling mares outside on pasture has been an effective practice in some outbreaks, presumably because there is less rotavirus contamination on pasture.

Image: Colourized TEM of rotavirus particles (source: CDC PHIL 173)

Infectious Agents In Foal Diarrhea

A new study was recently published in the Journal of Veterinary Internal Medicine (Frederick et al. 2009) which looked at infectious agents found in the feces of foals with diarrhea. Specifically, they looked for rotavirus, Clostridium perfringens, C. difficile, Salmonella, parasite eggs and Cryptosporidium oocysts.

They found at least one infectious agent in the feces of 122 (55%) of the 233 foals in the study. That means, despite testing for a wide range of pathogens, they could not identify an infectious agent in 45% of the diarrheic foals. This is very similar to the situation typically found in adult horses with diarrhea. This could have happened for a number of reasons:

  1. No test is perfect. It’s possible that in some of the cases one of the test results was a “false negative,” meaning it did not detect the infectious agent even though it was there.
  2. A few cases may have been caused by other infectious agents that were not included in the diagnostic panel.  For example, Rhodococcus equi is a common cause of respiratory disease in foals, but it has also been associated with diarrhea in some cases.
  3. The diarrhea was caused by an agent of which we are unaware, and for which we have no test. Researchers are constantly looking for other bacteria, viruses or parasites that may be capable of causing or contributing to diarrhea in foals and adult horses.
  4. The diarrhea was not caused by an infectious agent. For example, the authors failed to discuss foal heat diarrhea as a cause of clinical diarrhea in very young foals. This is a well recognized cause of foal diarrhea, but no infectious agents are involved.

The most commonly identified pathogens were rotavirus (20% of cases), Clostridium perfringens (18%), Salmonella (12%) and C. difficile (5%). Overall 191 (87%%) of the foals survived, and survival was not associated with any pathogen identified in the feces (i.e. in this study, foals were not more likely to die if they had one particular pathogen in their feces than another). This must be interpreted very cautiously, however, because the study does not account for other kinds of illness in these foals, or even whether diarrhea was the primary problem for which they were referred to the hospital. Diarrhea, especially in very young foals, can be very serious because they can dehydrate very quickly and are very susceptible to shock of various kinds.

There were a few other issues with this study that are important to keep in mind as well:

  1. The group of foals they looked at ranged in age from newborns to 10-months old. The digestive tract of a foal undergoes drastic changes in the first year of life, and it is well known that certain infectious agents only cause disease in foals of particular ages. For example, different parasites may take weeks to months to develop within the intestine of a foal, so even if a foal is infected as soon as it’s born, these parasites cannot cause disease for quite some time. For this reason, it would have perhaps been more useful to look at the data separately for different age groups.
  2. There was no control group in this study. Most of the time, if an animal has diarrhea and the test you perform tells you there is a known diarrhea-causing pathogen in the feces , you assume the diarrhea is due to that agent. This is not necessarily always the case. Some pathogens are carried around by totally normal animals, who may get diarrhea for a completely different reason. So what we really need to know now is: if the authors tested 233 foals with normal feces (and the same ages), how common would each of these pathogens be?

While the data may be interesting to look at, this paper doesn't really tell us anything new that will change the way we treat or manage foals with diarrhea in general.  Nonetheless, the information may still be useful for helping to design and interpret future research studies about these pathogens and diarrheal disease in foals.

Image source: www.bbc.co.uk (credit: George Ring)

Smectite: Diarrhea-Fighting Clay

Di-tri-octahedral smectite is a type of clay, but it's not just any old clay - it has some useful properties that may be able to help prevent or treat certain intestinal tract diseases. The main benefit of smectite is it's ability to bind to bacterial toxins. Bacterial toxins in the intestinal tract play an important role in intestinal diseases, particularly diarrhea. We previously showed that smectite effectively binds to toxins produced by Clostridium perfringens and Clostridium difficile, two important causes of diarrhea in horses, as well as endotoxin, another important bacterial toxin. These studies were done in a lab.  While smectite has been widely used for the treatment of diarrhea (or prevention in some situations), we've been using it based on the hope that what happens in the lab also happens in the horse, and on our clinical impression that it seems to do something helpful.

Now, we have a little more actual proof that this is the case. A recent study published in the Veterinary Journal (Hassel et al 2009) looked at the ability of smectite to prevent post-operative diarrhea in horses that underwent colic surgery. Horses were randomly assigned to receive smectite (500 g/500 kg body weight in 4 litres of water, once a day for 3 days) or a placebo (4 litres of water, once a day for 3 days). Treated horses had a significantly lower risk of post-operative diarrhea: 11% versus 41% in controls.

Surprisingly, there was no mention of whether treated horses had a higher survival rate, shorter hospital stay or other important outcomes. It would be useful to know these things, because if smectite just prevents mild diarrhea (i.e. the type that just results in loose feces for a couple days) but doesn't actually improve survival, decrease serious disease, shorten hospitalization or reduce complications, then it's not as useful.

So, we have more evidence indicating that smectite can have a beneficial effect in the horse, not just in the lab. Considering it's safe to use and not excessively expensive, and given that diarrhea is a serious problem in horses, continuing to use it makes sense. Nonetheless, more information about the ability of smectite to have an impact on survival, hospitalization, treatment costs or other factors is still needed.

Image source: www.platinumperformance.com

Weanling ADR (Ain't Doing Right)

We've survived the summer, and with cool(er) weather soon on its way we are now into what I like to call "weanling season" (which follows naturally after "foal season").  One of the common things veterinarians get called about at this time of year is 5-6 month-old foals that just "aren't right."  They may not be growing well, they may be skinny, they may not have the same healthy haircoat as other foals in the same group, and they may generally just be "dragging their heels" a bit - not very energetic, and maybe sometimes a little depressed.  Of course this is particularly problematic in the fall when some farms are trying to get their foals ready for sale, and they want them looking their best!

Bloodwork on these scraggy foals often shows low - sometimes extremely low - protein levels in their blood.  Blood protein is very important for normal body function and controlling tissue fluid levels, and the body (especially the liver) works very hard to maintain normal levels.  Low blood protein (also called hypoproteinemia) in these animals usually indicates that the protein is being lost from the body, and the most common route for this to happen is through the intestine. (It can also be lost through the kidneys, but renal disease in young animals is generally uncommon.)  Some of these foals have diarrhea as well, or may go on to develop diarrhea if left untreated.

What is it that turns a foal's intestine into a protein sieve?  One possibility, and a hot research topic at the moment, is the bacterium Lawsonia intracellularis, which causes the condition known as proliferative enteropathy.  But any severe infection of the intestine has the potential to affect the barrier that normally keeps blood protein fluids in the bloodstream, so other causes of enteritis and colitis such as Salmonella and Clostridium also need to be considered.  Heavy burdens of intestinal parasites can cause similar problems - some of these may be difficult to test for because the larval stages do not produce eggs that can be found on a fecal test, and developing resistance issues mean that routine deworming cannot guarantee that parasites are not present.  There are no doubt other causes as well that haven't been identified - in half of all diarrhea cases in (adult) horses, a causative agent cannot be identified, even with a complete diagnostic work-up. 

In horses, if only the small intestine is affected (enteritis) - even in severe cases - the animal usually will not have diarrhea.  However, if the infection spreads to the colon, or if the bacterial populations in the colon are affected badly by the foal's poor health status and abnormal "flow" of feed material due to the infected intestine "upstream", then colitis will develop as well, resulting in diarrhea.  Anytime the normal intestinal bacteria of a horse are disrupted, the animal also becomes more susceptible to other bacterial pathogens such as Salmonella and Clostridium as well.

What should be done with these "scraggy" weanlings?

1. Have them examined by your veterinarian as soon as possible.  Don't wait for them to start looking really sick.  These weanlings can be frustrating to diagnose and treat at the best of times, but the farther they're allowed to slip, the harder it is (and the longer it takes) to bring them back.

2. Look for other foals that might be affected.  Especially in larger groups of foals, one particularly sick animal may stand out, but there could be several others flying just under the radar that you may not notice unless you really take the time to look at each foal individually.

3. Separate healthy weanlings from those that aren't 100%.  It may be difficult or impossible to individually isolate all the "scraggy" animals depending on numbers and the facilities available, particularly more severely hypoproteinemic foals that may take weeks to months to recover.  At a minimum, the foals that appear healthy should be separated from and always handled before the ones that may be affected by an intestinal infection.  Any animal with diarrhea should be isolated.  The duration of isolation required will depend on the specific diagnosis (if one can be made).

More information about Lawsonia is available on the equIDblog Resources page and in our archives.

Image source: www.virginiawildhorserescue.com

How To Prevent Antibiotic-Associated Diarrhea

Horses sometimes need to be treated with antibiotics. That's an unavoidable fact. Some horses that are treated with antibiotics develop diarrhea, which can be fatal. That's another unavoidable fact. While those two situations can't be avoided, the risks can be decreased.

Addressing the first point, "sometimes horses need to be treated with antibiotics," involves various factors such as having a good preventive medicine program, good infection control and only using antibiotics when they are truly needed. We'll never absolutely eliminate the need for antibiotics, but we can reduce their use.

The second point is a little harder to address. Any horse being treated with antibiotics is at some risk of developing antibiotic-associated diarrhea. In addition to hopefully killing or inhibiting the bacteria at the site of the infection, antibiotics also reach the intestinal tract, where there can have effects on the complex resident bacterial population. Disruption of this normal bacterial population can allow "bad" bacteria to overgrow, resulting in diarrhea. How do we reduce the risk?

  • Use antibiotics only when necessary and with the advice of your veterinarian.
  • Avoid high-risk antibiotics (e.g. tetracyclines, erythromycin in adult horses) unless absolutely required.
  • Use local (i.e. topical) therapy whenever possible instead or oral, intravenous or intramuscular administration. This limits the amount of antibiotic that makes it to the intestinal tract.
  • Try to minimize other potential risk factors for diarrhea such as diet changes, high grain diets, transportation and other stresses.
  • Monitor your horse closely and contact your vet if there are any signs of colic or diarrhea.
  • It might be reasonable to avoid anti-ulcer drugs, since it's possible there could be increased risk of diarrhea while being treated with these drugs (possible, but not proven).

Probiotics are often used, but there is currently no evidence they are effective in horses. Mixed results have been obtained in people.  It's possible that certain probiotic organisms at certain doses may help reduce the risk of certain types of diarrhea in certain horses. We just don't know what "certain" means at this point. Probiotics probably won't hurt, but we can't have any confidence in them yet that they are really beneficial.  No other supplements have been shown to be effective, and there is little reason to suspect that any would be effective.

Chickens, Campylobacter, Ulcers and Horses

What's the link between chickens, Campylobacter, anti-ulcer drugs and horses? Well, nothing direct but a recent paper in the journal Emerging Infectious Diseases provides more evidence that the use of proton pump inhibitors for treatment and prevention of gastric ulcers can be associated with increased risks of certain types of infectious diarrhea in people. People who used this type of acid-suppressing drug were more than 3 times as likely to have Campylobacter diarrhea than people who didn't. Biologically, it makes sense. The acid barrier of the stomach is designed to kill harmful ingested bacteria, and decreasing that acid barrier through the use of acid-suppressing drugs can help bacteria survive passage through the stomach and subsequently cause diarrhea when they reach the intestines. It's been reported as a risk factor for Clostridium difficile diarrhea as well.

But does this apply to horses? We don't know. Infectious diarrhea is certainly a problem in this species, but no studies have looked at whether anti-ulcer drugs like omeprazole (Gastrogard) are a risk in horses. It makes sense that they could be but there's currently no proof. The reason I've been concerned about this is that anti-ulcer drugs are sometimes used like candy, when there's no clear evidence that they're necessary. These are important drugs for certain horses and are crucial for treatment in horses with ulcers. However, a lot of other horses receive anti-ulcer drugs prophylactically, and it's unclear whether the possible benefits of ulcer prevention therapy outweigh the potential risks of infectious diarrhea.

Without any clear evidence, the key is to weigh the potential risks and benefits. If your horse has ulcers (especially severe ones like in the gastroscopy picture above), then it certainly should be treated. If it has recurrent ulcers that keep coming back, prophylactic treatment may be useful, but management changes should also be made if possible to reduce the risks. In horses that do not or have not had problems with ulcers, I'm not convinced that routine anti-ulcer treatment is needed (or even a good idea). In certain situations where the risk of exposure to an infectious cause of diarrhea is higher (e.g. diarrhea outbreak on the farm, admission to an equine hospital) or when the horse has other risk factors for diarrhea (e.g. antibiotic treatment), I'd be especially wary.

Remember: While anti-ulcer drugs are useful, they may have a downside, like most other drugs.  You need to think about both aspects (risks and benefits) when deciding whether to treat or not.

Foal Diarrhea Part 2: Foal Heat Diarrhea

As previously discussed, diarrhea in young foals can range from a messy inconvenience to a rapidly life-threatening condition. A very common but fortunately relatively harmless cause is a syndrome called foal heat diarrhea, so named because it usually occurs around the time of the mare's first heat after foaling, when the foal is about 7-10 days old. Foals with foal heat diarrhea have diarrhea but no other problems like weakness, decreased appetite, colic or fever. If any of these other signs are present, then the foal has something other than (or in addition to) foal heat diarrhea.

The cause of foal heat diarrhea is not known. It doesn't actually have anything to do with the mare's heat, or the mare at all in fact - it even occurs in foals that are bottle raised and have no contact with a mare. It's likely the result of normal changes in the bacterial microflora in the intestinal tract of the foal that just happens to occur at this age.

Foals are usually diagnosed with foal heat diarrhea when they are the right age and have mild diarrhea but no other problems. Testing for (and ruling out) other causes of diarrhea like salmonellosis helps to support this diagnosis.

Any foal with diarrhea must be monitored closely for developing signs of illness.  Don't fall into the trap of simply chalking up a diarrhea episode to foal heat diarrhea and forgetting about it.  If you're wrong, a foal with diarrhea due to an infectious cause can go from looking "okay" to too weak to stand and nurse (or worse) within a matter of hours.

Foal heat diarrhea does not require any treatment in almost all cases. Occasionally, foals can get weak or dehydrated if they don't drink enough to make up for the fluid lost in the diarrhea, but this is quite rare. Foals almost always get better on their own. If they don't, there is probably something else going on and diagnostic testing is needed to determine what that is.

The fact that foal heat diarrhea gets better on its own may be one reason there are so many "proven" foal diarrhea treatments by which people swear. Some people are convinced that certain treatments are highly effective because when they treat foals, they get better. However, with foal heat diarrhea, which is probably the most common cause of diarrhea in foals, the animals get better regardless of (or despite) what you do. That's why well-designed research trials that include untreated control groups are needed to determine if treatments actually work.

Foal Diarrhea Part 1: Clostridium difficile

Diarrhea is a relatively common problem in foals. It can range from very mild to fatal, and sick foals can get worse (i.e. "crash")  very fast. Outbreaks of diarrhea in foals can also occur.  So while most cases of foal diarrhea are mild, the implications of this condition for both the foal and the farm can be huge.

There are a variety of potential causes of diarrhea in foals. One is Clostridium difficile, a bacterium which can be found in the intestinal tract of a small percentage of healthy adult horses and foals, but which can also cause disease under certain conditions. Clostridium is a type of spore-forming bacterium - it produces spores that are able to survive for a very long time (i.e. years) in the environment, and that are resistant to most disinfectants. Most cases of C. difficile infection in foals are single, sporadic cases, but outbreaks on breeding farms can occur and can be very difficult to control. Typically such outbreaks start out with a few individual (sporadic) cases of foal diarrhea early in the foaling season, with a gradual increase in the number of cases over the following weeks to months. Often it gets to the point that  all foals born later in the season develop diarrhea. You cannot tell the difference between diarrhea caused by C. difficile and that caused by other infectious agents just by examining the foal - diagnostic tests are needed to make the diagnosis (watch for an upcoming post for more information about this kind of testing).

There is little information about control measures for C. difficile infection that have been proven to work. However, our understanding of the organism and what it does in horses and other species lets us make some general recommendations:

  • Only use antibiotics when it's really necessary. "Routine" use of antibiotics in foals (which some people use to try to compensate for poor management practices) is not needed, and may increase the risk of C. difficile.
  • Use good general hygiene practices, particularly around the time of foaling and in areas where neonatal foals live or often are. Clostridium difficile is spread by the fecal-oral route, meaning foals swallow the C. difficile from manure contamination in their immediate environment.
  • Isolate all horses (foals and adults) with diarrhea so that they are less likely to spread it to other horses.
  • Do not try to treat healthy horses or foals to try to get rid of C. difficile. There's no evidence that it works and it could actually make it more likely that the horse/foal will get sick.
  • Let your veterinarian run the appropriate diagnostic tests to identify the cause of diarrhea in any adult horses or foals, particularly on farms where more foals are expected to arrive. It's better to find out early with what you are dealing, in case specific preventive or early treatment measures can be used to help stop an outbreak from occuring.
  • Make sure you have a good infection control program for your farm.

No vaccine for C. difficile is currently available, nor will one be available in the near future. Other techniques for preventing this disease are being evaluated but none are yet proven.

More information about Clostridium difficile can be found on the equIDblog Resources page.

Disease Surveillance in Equine Hospitals

Infectious disease surveillance is an important part of the infection control program. Equine hospitals with good infection control programs have put thought and effort into designing a surveillance program that is right for them. Like many (or most) aspects of infectious diseases, there is no "standard" program, because the risks and benefits vary greatly between facilities.

There are various types of surveillance that can be used. Here are some examples:

Active surveillance
This involves going out and "actively" collecting information that would not otherwise be collected for other reasons. This includes things like taking extra samples from horses for testing strictly for infection control reasons. This is discussed further below.

Passive surveillance
This involves using data that are already available. It's a cheaper and somewhat easier form of surveillance, but it doesn't provide as much detailed information as active surveillance. An example of this is compiling all the culture results from fecal samples that were already submitted for routine testing (as required by the case).  This helps us know what bugs tend to cause certain infections, and to what antibiotics they are usually susceptible.

Syndromic surveillance
Syndromic surveillance can be active or passive. It involves looking at the occurrence of specific clinical signs (syndromes), not specific diseases/diagnoses. For example, routine monitoring for fever in hospitalized animals is a useful tool. It doesn't tell us what the specific problem is, but it can alert us that something might be going on.

I'll outline the active surveillance component of the Ontario Veterinary College's active surveillance program here (I'll get to the other types some other time):

Salmonella

  • All horses that are at high-risk for shedding Salmonella in their feces (i.e. horses with colic) and all horses that are at increased risk for becoming infected (i.e. horses undergoing anesthesia and surgery) are tested.  Horses with diarrhea - the highest risk group for shedding Salmonella - are also tested as part of the routine case work-up.
  • Stalls that have housed diarrheic horses are quarantined until they have been tested for Salmonella. The stall environment is sampled and culture is performed. Stalls are not opened until negative culture results are received.

Methicillin-resistant Staphylococcus aureus (MRSA)

  • A nasal swab is collected from all horses at the time of admission, weekly during hospitalization (if they stay that long) and at the time of discharge.

Other

  • Additional active surveillance for Salmonella and MRSA can be conducted at the discretion of the Chief of Infection Control (i.e. me). If I have any concerns about a particular disease, I institute additional active surveillance.

Who pays for it?
Active surveillance costs (as opposed to routine diagnostic testing like Salmonella culture in a horse with diarrhea) are covered by the Hospital. It's a cost of doing business. Financially, it also makes sense, because it is cheaper to prevent infections than it is to deal with hospital-acquired infections and outbreaks.

Don't be afraid to ask about the infection control program at your equine hospital. A hospital should be more than willing to tell you what they're doing to help reduce the risk of your horse developing an infection.

More information on equine hospital infection control can be found in on the equIDblog Resources page.

Oral Antibiotics in Horses

In people, as well as many other species like dogs and cats, oral antibiotics (e.g. liquids or pills that are swallowed) are very commonly used, because it's usually easier (and less uncomfortable) than giving antibiotics by injection with a needle.  A wide range of oral antibiotics are available for use in humans, and while antibiotic-associated complications such as diarrhea certainly can occur, oral antiboitics are relatively safe for most people.

So, why don't we use many oral antibiotics in horses?

Horses have a very different intestinal tract than people (and dogs and cats). A horse's intestinal tract is much likely to develop problems from antibiotic use, particularly antibiotic-associated diarrhea or colitis, which can be fatal. The root of the problem in these cases is  disruption of the normal bacterial populations that live in the intestine (the microbial "flora"), which can allow harmful bacteria to multiply and spread. This can occur with antibiotics given by any route (even by injection), but using oral antibiotics can result in higher drug levels in the intestinal tract, which creates a greater chance of causing problems. The likelihood of a horse developing complications from any antibiotic is probably a combination of what bacteria the antibiotic kills and how much makes it to the intestinal tract.

  • Some oral antibiotics can be used relatively safely in horses. Trimethoprim sulfa (TMS) is very commonly used, and quite safely for the most part, in many areas (including Ontario).
  • Chloramphenicol and enrofloxacin (Baytril) are also given orally to horses, but these drugs should be reserved for problems for which they are specifically indicated.
  • Some antibiotics can be used more safely in foals than adults, such as erythromycin. While diarrhea can occur in foals, erythromycin (and related drugs in the macrolide class) are commonly used without problems in young stock. Macrolides are higher risk drugs in adult horses. I've used them a few times in adults when I've had no other choice, but it's always a scary prospect.
  • Never use an oral antibiotic that is not known to be relatively safe for use in horses. One of the first cases that I saw during my residency was an expensive racehorse owned by a physician. He had cultured a minor foot wound and grown a Staphylococcus that was susceptible to cloxacillin. He got some cloxacillin and gave it to the horse orally - something no veterinarian would do. The horse developed severe diarrhea and died despite intensive treatment.

Infections in Neonatal Foals

Infectious diseases are a major problem in young foals. Diseases, including diarrhea, pneumonia, meningitis, umbilical infections and joint infections can range from mild to rapidly fatal.  Even in foals that survive the initial infection, these conditions can sometimes result in permanent problems. A study published in a recent edition of the Equine Veterinary Journal (Wohlfender et al, 2009) looked at infectious diseases in the first 30 days of life in 1031 foals on 36 breeding farms in the Newmarket, UK area. This very large study provided some interesting information:

  • The overall incidence of infectious diseases was 8.3%, meaning around 1 in 12 foals developed some type of infectious disease during the first 30 days of life.
  • The most common infectious problem was diarrhea, which occurred in 5.9% of foals. Foals with diarrhea that didn't have other signs of illness were not included.  This is because most young foals with diarrhea and no other abnormalities likely have foal heat diarrhea, which is not an infectious disease.
  • Umbilical infections developed in 0.7% of foals.
  • Joint infections occurred in 0.4% of foals.
  • Bone infections occurred in 0.2% of foals.
  • Respiratory infections were uncommon, occurring in only 0.6% of foals.
  • There was no difference in the incidence of infections in foals that were treated routinely with antibiotics to "prevent" infections. Whether or not this practice is effective has been a controversial issue for a long time.  The best way to answer the question would be to have a study that randomly assigned foals to receive antibiotics or no antibiotics, and then monitored both groups for infections.  This study didn't do that, so there could be some "bias" to this particular finding, but the results are still useful. I don't find the results surprising - there has never been good evidence that antibiotics are routinely needed in newborn foals. This study may help control routine (and in my opinion unnecessary) antibiotic treatment in healthy newborn foals.

This study provided more information confirming that infectious diseases are a significant problem in foals, and that measures are needed to reduce the incidence of infections. It also provided evidence that routine antibiotic use is NOT an effective means of doing this. While there is a lack of good, objective evidence, routine hygiene, sound management and every-day infection control practices are probably critical factors for infectious disease prevention in these young animals.

Champion Australian Racehorse Dies of Colitis

James Matthew, a champion Standardbred pacer from Australia, died this morning (Feb 25) of colitis. He originally had a suspected viral infection, then developed colitis (severe diarrhea). Despite aggressive care in a veterinary hospital, he died. The causes was reported as "colitis X".

Colitis X is a term that I don't like, and one that I (and many other people) have stopped using. For me, it's a fancy way of saying "it's severe diarrhea and I don't know what caused it.'" Clinically, colitis X is characterized by severe diarrhea and varying degrees of dehydration, toxemia, abdominal pain and shock. Affected animals often die very quickly despite extremely intensive treatment.

Colitis X is not a specific disease. It is probably caused by one (or a combination) of many intestinal pathogens such as Salmonella, Clostridium difficile, Clostridium perfringens and likely many other bacteria. It is often associated with antibiotic therapy, and I wonder whether this horse was treated with antibiotics. (I'm not saying it's the case here, but unfortunately, many horses with viral infections are treated with antibiotics unnecessarily.)

Treatment of severe colitis can be very difficult. These horses are very sick and tend to respond very poorly to any treatment. We can use extremely aggressive fluid therapy, running in as much fluid as is physically possible, and still not keep up with the amount of fluid they lose. They often shown signs of severe shock, they lose tremendous amounts of protein through their intestinal tract, and can develop severe complications like laminitis (founder).

Prevention of severe colitis is also difficult. Antibiotic treatment is certainly a risk factor and we should try to limit antibiotic use to only when absolutely necessary. However, some horses develop severe colitis for no apparent reason, and there's not much we can do about it in those cases.

More information on Clostridium difficile can be found on the equIDblog Resources page.

Diarrhea: Why Culture?

Diarrhea is a potentially life-threatening condition in horses. It's also frustrating from a diagnostic standpoint because, even with the most complete/comprehensive testing, a cause is only identified in a minority of cases. This is true for other species too, including people, and is a reflection of the complex nature of the intestinal tract and the numerous possible causes of intestinal disease. Diagnostic testing obviously costs money, so if it gives us an answer less than half the time anyway, it begs the question - why bother? Well, here are some points to consider:

  • In some situations, you may find a cause that requires a different treatment, so diagnosis has a direct impact on patient care and probably the outcome.
  • Many causes of diarrhea are infectious and it's important to know if other horses may have been exposed to a transmissible pathogen.
  • Some causes of diarrhea, especially Salmonella, can also infect people, and it's important to know to what people have been exposed.
  • It's also important to know whether a horse might still be shedding a transmissible pathogen after its diarrhea resolves. For example, horses with salmonellosis can shed Salmonella for a while (often a few weeks, sometimes longer) after they have recovered from their diarrhea. This could be a source of infection for other horses and people.
  • Outbreaks of diarrhea can occur. It's much better to know early on what you are dealing with, rather than waiting until mulitple horses have been infected.

I consider diagnostic testing money well spent in cases of diarrhea. Some people don't want to test because they don't want to know, particularly about Salmonella. However, it's been proven again and again that the "head-in-the-sand" approach will backfire when it comes to infectious diseases.

Reading Probiotic Labels

I commonly get asked about giving probiotics to horses, and what I recommend. While probiotics are often simply described as "good bacteria", a better definition is "live microorganisms that, when ingested in certain amounts, cause a positive health effect beyond that of their nutritional value." This definition makes it clear that there must be live microorganisms, they must be given at a certain dose and they must cause a beneficial effect. Unfortunately, while there are many, many probiotics available for use in horses, and lots of money spent on the marketing of such products, there has been basically no real research done on any commercial equine probiotic. That makes it difficult to make good recommendations. Studies have also shown that commercial probiotics often don't even contain what they say they do. So, what do I say when I'm asked? I say it probably won't hurt to give an adult horse a probiotic (one study in young foals showed that a probiotic actually caused diarrhea), but there is no guarantee that it will help either. One thing that I do recommend is always to read the label closely.

The label of a probiotic product should clearly state:

  • Which organisms the product contains (and they should spell all the organisms' names correctly (don't laugh, it happens!)).
  • How much of each organism is present (this is often measured in CFUs or colony-forming units).
  • An expiry date.
  • Whether the numbers of organisms are guaranteed to be present at expiry - sometimes the stated number of organisms is what was put into the product, with no understanding (or guarentee) of whether they will still be viable at the time of use.
  • No excessive claims of effectiveness. (My general rule is that something that promises to cure everything, it probably cures nothing!)

While a good label is certainly no guarantee that the probiotic will work, it seems logical that companies that can't even get the label correct probably aren't making a good product either. We did a study on this a few years ago, for which we simply bought a variety of commercial probiotics and read the labels. I wasn't sure whether to be amused or disgusted by the results, but I certainly wasn't amazed:

  • 35% of veterinary and 43% of human products improperly identified their contents. Many used vague (and useless) descriptions like "probiotic cultures." It wasn't even clear in some of the products if live bacteria were expected to be present.
  • In 18% of veterinary products that listed bacterial species, the names of the organisms were misspelled.
  • Bacterial species were misidentified in 35% of veterinary products, including claiming to contain bacteria that do not exist.

So, probiotic are very much "buyer beware." Until consumers start demanding proof from companies that their products are effective, we may not get much new information.

More information on probiotic use in horses can be found on the equIDblog Resources page.

Diarrhea in Horses: More Than Just A Mess

Diarrhea is a relatively common problem in many animal species (including people). It's often mild and typically goes away on its own, and is more of a cosmetic or convenience problem than a serious health concern. However, that's not necessarily the case in horses. Although horses can get mild diarrhea that gets better on is own, severe diarrhea (colitis) is a very serious problem that can even be fatal. There are many potential causes of diarrhea in horses, including Salmonella, Clostridium difficile, Clostridium perfringens, Neorickettsia risticii (Potomac Horse Fever) and Lawsonia intracellularis. It is likely that numerous other bacteria can also cause diarrhea, but we just don't know how to diagnose them.  In fact, a specific pathogen is identifed as the cause of diarrhea in horses in less than 50% of cases.

Diarrhea can be rapidly life-threatening in horses. Some reports have described fatality rates as high as 40%, however these are based on cases from referral hospitals which presumably treat the sickest horses. Nonetheless, this high fatality rate needs to be taken seriously. In severe cases, death may occur in less than 24 hours, and may be due to the intestinal disease itself, or any number of complications that can accompany colitis.

The picture (left) is of the intestinal tract of a six-month-old foal with severe diarrhea that threw a blood clot to one of the major blood vessels suppling the large intestine, killing that section of the gut (the dark purple/black intestine in the picture), and the foal. Laminitis (founder) is also a common complication.

There is no way to completely prevent diarrhea from occuring in horses, but some basic measures should help reduce the risk:

  • Only use antibiotics when absolutely necessary, and only when prescribed by your veterinarian. Antibiotic-associated diarrhea is big problem in horses.
  • Avoid sudden management changes, such as feed changes and transportation, as much as possible.  If something needs to be changed, try to introduce the change(s) as slowly as possible.
  • Isolate new arrivals so that the risk that they will introduce pathogenic bacteria like Salmonella to other animals on the property is reduced.
  • Have a good basic infection control program in place to reduce the risk of transmission of infections of all types.
  • Immediately isolate all horses with diarrhea, and contact your veterinarian.

Lawsonia intracellularis - New Horizons

On December 9, the Infectious Diseases session was held at the 2008 AAEP Conference in San Diego, CA. Topics presented covered several conditions, including MRSA, Clostridium difficile, equine infectious anemia (EIA), parasite resistance and deworming protocols, and Lawsonia intracellularis.

Lawsonia intracellularis is a bacterium that causes a disease called (among other things) proliferative enteropathy in foals and weanlings. More information about this disease is also available on the equIDblog Resources page. This disease is relatively new in the horse world, being first identified in the 1990s. It has traditionally been considered a disease of pigs, where it causes several syndromes of clinical disease, including one similar to that seen in foals. In pigs that carry the bacteria in their intestine, clinical disease is brought on by stressful events, and the same may be true in foals. The infection causes severe thickening of parts of the small intestine, and the inflammation causes loss of large amounts of protein from the bloodstream. Affected foals are usually very “unthrifty” and quiet/depressed, and many often develop edema (non-painful, cool swelling) along their abdomens or under their jaws.

In pigs, prevention of disease due to Lawsonia infection involves decreasing stressful events and vaccination with an oral vaccine. Dr. Nicola Pusterla of the University of California (Davis) presented the results of a study that was done recently looking at the effects of vaccination of foals against Lawsonia in three different ways – giving the vaccine orally, giving the vaccine orally after treating the foals for three days with a gastroprotectant (omeprazole), and giving the vaccine rectally. The reason for the last two groups was to decrease the risk of the vaccine being destroyed by the acidic environment of the normal stomach. Indeed, they found the antibody response to the vaccine in the bloodstream was better in these groups than in the untreated foals that were given the vaccine orally. Of the 12 foals that received the vaccine, all of them stayed healthy throughout the study period (42 days).

Although seeing some work on developing a vaccine for this disease is great, we are still a long way from being able to use vaccination to prevent disease in foals. While the animals in the study produced antibodies in the bloodstream, Lawsonia actually lives inside cells, where antibodies usually cannot get to them. Immunity against intracellular pathogens like this requires cell-mediated immunity, which is much harder to measure. It’s also important to remember that even with a vaccine, control of this disease (as with any infectious disease) depends on a lot of other factors, like reducing stress on animals and preventing transmission and spread of the bacteria. Unfortunately, no one is even sure exactly what the source of the Lawsonia is in most foals (although there’s a good chance that they ingest it, possibly with fecal contamination from foals that are shedding Lawsonia).

As more and more cases of Lawsonia are seen, both in North America and now in Europe, researchers will continue to learn more about how this disease is spread, and hopefully one day develop a vaccine to help us prevent it.

Keep watching this site for more of the latest and greatest from the 2008 AAEP Conference!

Anti-Ulcer Therapy and Diarrhea

Stomach ulcers are common in horses (especially race horses), and anti-ulcer medications are widely used. The most common of these drugs is omeprazole (sold under the brand name Gastrogard), which is a proton pump inhibitor. There is no doubt that gastric ulcers can cause problems in horses and treatment is necessary in these situations. However, there are a lot of horses being treated for mild ulcers or for prevention of ulcers, and it's unclear whether this is really needed, and whether it could even cause problems.

Picture (right): Endoscopic view of ulcers along the margo plicatus in the stomach of a horse.

In people, proton pump inhibitor treatment has been associated with an increased risk of diarrhea (particularly Clostridium difficile diarrhea). Biologically this makes  sense.  The acidic environment of the stomach normally helps kill harmful bacteria that a person (or a horse) may ingest. Treatment with anti-ulcer drugs to reduce the acidity of the fluid in the stomach may allow bad bacteria like Clostridium difficile and Salmonella to reach the intestinal tract in larger numbers, and therefore predispose the patient to developing diarrhea.  Theoretically the same thing could happen in horses.

Does this actually happen in horses? We don't know. It is certainly a possibility but there is no evidence either way.

Are certain horses at higher risk? We don't know. However, it's reasonable to suspect that this could be a greater concern in horses that are already at higher risk of developing diarrhea for other reasons, such as those being treated with antibiotics.

Should we avoid using anti-ulcer drugs in horses? Not always. These drugs are definitely needed for horses with clinically significant ulcers (i.e. their ulcers are actually painful or making them sick). However, we really need to consider whether treatment is necessary for horses that have very mild ulcers (i.e. that aren't causing clinical signs) or those that don't have ulcers at all and treatment is only "preventative".

Personally, I don't like to use anti-ulcer drugs in hospitalized horses unless they have severe ulcers that are causing problems. In cases where milder ulcers are present or people want to give anti-ulcer drugs for prevention, I prefer them to wait until the horse goes home. The same approach could be taken with horses that are on farms but at higher risk for diarrhea, such as those being treated with antibiotics.

Cipro Warning: Stay Away!

I've had a couple questions lately about ciprofloxacin (also called "cipro"), so I thought it might be a good time to make a few comments about this drug. Cipro is an antibiotic that is very useful in many species. Unfortunately, this does not include horses.

I am aware of only two published papers about the use of cipro in horses (other than topically on the eyes). The first was a study that showed when you give cipro orally to ponies, they don't absorb it well enough from their intestines to reach therapeutic levels in the rest of the body.  Therefore, the drug won't work effectively against any bacterial infection in the rest of the body. The other paper described a series of four horses that developed severe (and sometimes fatal) diarrhea after being treated with cipro. So, if the drug isn't absorbed well enough to kill any bacteria in the horse's body, but it can still kill bacteria in the intestinal tract and cause fatal diarrhea, we really shouldn't be using it. Sounds logical enough.

Yet it seems that cipro is still being used in horses. I've heard that lower doses are being used because they are less likely to cause diarrhea. That's probably true, but if higher doses couldn't produce levels of the drug that would kill bacteria in the body tissues, then lower doses certainly won't.  While the risk of diarrhea may be lower with lower doses, the chances of having any desirable effect on an infection are probably close to zero. Horses that get better while being treated with cipro probably didn't really need an antibiotic in the first place - they are getting better in spite of being treated with cipro, not because of it.

Antibiotics are important and sometimes life-saving drugs, but treatment always comes with some degree of risk, no matter which drug is chosen. However, there are still many effective antibiotics that, over time, have been shown to be lower risk than others.  We should stick with these as much as possible, and not resort to a drug like ciprofloxacin that, based on current evidence, is likely to do more harm than good.

Tags:

Helpful vs Harmful: Antibiotic Risks in Horses

The discovery of antibiotics was one of the most important medical advances in history, and these drugs have had an immense impact on human and animal health. While antibiotics have saved countless lives, their use can also be associated with some very serious side effects and complications.  For example, in horses, antibiotic-associated diarrhea (colitis) is a major issue.

By the nature of their intestinal tract, horses at among the highest risk species for developing serious diarrhea associated with antibiotic use.  The intestinal tract of a horse is full of billions of bacteria of different types. These bacteria are important for normal digestion, and also help to prevent infection by "bad" bacteria such as Salmonella and Clostridium difficile.  Antibiotics can disrupt the balance of this complex bacterial population.  The imbalance itself can cause problems, and can also make it easier for bad bacteria to move in, grow and cause disease.

Here are some important points to remember about antibiotics, particularly in horses:

  • Antibiotics can only kill bacteria. They should not be used when a bacterial infection is not present and not likely to occur. Antibiotics are too commonly misused for viral infections in horses, which puts the animals at unnecessary risk.
  • Any antibiotic can cause diarrhea, but some drugs are considered higher risk. Erythromycin and tetracyclines are considered high-risk in most areas of North America. Certain drugs, such as lincomycin and oral penicillins, are such high risk that they should never be used in adult horses.
  • Both oral and injectable antibiotics can also cause diarrhea. Drugs that are injected can still reach the intestinal tract and affect the bacteria there. Some drugs, like tetracycline, are actively pumped into the intestinal tract from the bloodstream, resulting in relatively high concentrations in the intestine, even if the drug was given by injection.
  • While some antibiotics can be purchased over the counter in some areas, antibiotics should never be given without the direct recommendation of a veterinarian.
  • If your horse is being treated with antibiotics and develops diarrhea, contact your veterinarian immediately.
  • There is no known way to reduce the risk of antibiotic-associated diarrhea in horses, other than to avoid unecessary use of antibiotics. Some people treat horses with probiotics or yogurt, but currently there is no evidence that this is beneficial (but it probably doesn't hurt, at least in adult horses).

Another major concern with antibiotic use is the development of antibiotic resistance in bacteria, but that's a topic for another post (or two, or three or more!).

More information about Clostridium difficile and probiotics in horses can be found on the equIDblog Resources page.

Equine Infectious Disease Information Sheets

Click on any of the highlighted links below for more information about these horse-related infectious disease topics. Topics that are not highlighted are in development and coming soon. New information will be added as it becomes available, so be sure to check this page regularly for the latest updates.

Bacteria Viruses Parasites Other
Clostridium difficile Rabies Bots Pleuropneumonia
Clostridial Myonecrosis Eastern Equine Encephalitis Equine Protozoal Myeloencephalitis (EPM) Neonatal Diarrhea
Strangles (Streptococcus equi) Equine Herpesvirus Cyathostomes
(Small Strongyles)
Needlestick Injuries
MRSA Equine Influenza Large Strongyles Colostrum
Lawsonia West Nile Virus Tapeworms  
Rhodococcus equi   Pinworms  
Tetanus      
Botulism -
Feed-Associated
     
Botulism -
"Shaker Foals"
     
       
       


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