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

Severe Diarrhea Caused By Clostridium difficile

The latest issue of the Journal of Veterinary Diagnostic Investigation contains a case report by Dr. Glenn Songer's research group about a 14-year-old Quarterhorse that had been treated with ceftiofur (an antibiotic) because of suspected salmonellosis, and subsequently died of severe colitis (sometimes called colitis X, but I don't like that name). This pattern is all too familiar when it comes to horses: antibiotic treatment for an undiagnosed infectious disease results in death due to colitis (diarrhea). It's even more frustrating when you consider there is very little indication to treat adult horses with salmonellosis with antibiotics.

The colitis in this case was caused by Clostridium difficile.  The strain of C. difficile was ribotype 027 (also called NAP1, BI and toxinotype III, depending on the method used to type the strain), which is typically considered the most serious strain in people. It is often associated with outbreaks of disease, and has been blamed for the increased frequency and severity of C. difficile infections in people internationally over the past few years. This strain has also been found in dogs, cattle and pigs, as well as retail meat samples (e.g. from the grocery store).

While the information in this paper isn't particularly surprising, it should act as a reminder that C. difficile is an important problem in horses and that important strains of C. difficile can infect many different animal species. When you consider how big of a problem C. difficile is in human medicine, it should be a reminder that we need to take this problem seriously in horses too, and also continue to investigate whether people can be infected by horses. A small percentage of healthy horses shed C. difficile in their manure, and we don't really know if that poses a risk to people. When you consider how much C. difficile can be present in diarrhea, the huge volume of diarrhea that a horse can pass and the potential for human exposure because of the big mess that is made, we certainly should consider diarrheic horses as a possible source of infection for people, just as we do for Salmonella.

Antibiotic use is a well known trigger for C. difficile infection in people.  While disease in horses can occur even when antibiotics are not given, it is widely suspected that antibiotic use is a major risk factor for severe colitis due to C. difficile. Anecdotally, ceftiofur seems worse for this than many other drugsin some regions.  This is consistent with studies in humans that have shown that antibiotic drug class used can have a significant impact on the risk of C. difficile infection.

What should we take home from this report?

  • Only use antibiotics when they are really needed. Antibiotic administration can lead to fatal complications, although these are rare.
  • Consider C. difficile in all cases of diarrhea in horses.
  • Consider all horses with diarrhea potentially infectious to other horses and people, and handle/house them appropriately.

Photo source: http://www.microvet.arizona.edu/Faculty/songer/diag.htm

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.