Powerful drugs must be used judiciously to avoid serious side effects in horses
by Kenneth L. Marcella, D.V.M.
ANTIBIOTICS are powerful and extremely useful drugs that have been largely influential in increasing both the quality and the length of life in horses. They are necessary in many conditions to:
•Help foals recover from devastating respiratory infections;
•Help broodmares eliminate uterine problems to remain fertile; and
•Keep athletic horses from developing bone and joint disease following trauma or reparative surgery.
But antibiotics are still drugs. As such, they also can have damaging side effects, and their use is a constant balance between the good accomplished and the potential for serious consequences.
One of the most serious side effects seen with the use of antibiotics in horses is the development of colitis, an inflammation of the membranes lining the large bowel of the intestine. Normally, this tissue lining is responsible for the secretion of mucus, enzymes, and digestive factors, as well as the resorption of water and certain electrolytes. Colitis can be acute and develop in a matter of hours, or it can be chronic, taking several days to develop and lasting for months.
Colitis's many causes
Many factors can cause colitis, including bacteria, viruses, and parasitic organisms. Bacterial colitis is perhaps the most common.
The horse's intestines are designed to contain a large population of normal bacteria, or flora, that digest grass, hay, and grain. These bacteria are responsible for breaking down what the horse eats into smaller particles--carbohydrates, fatty acids, and proteins--that the horse's body then uses. Toxins are produced as a normal byproduct of bacterial action during digestion. Normally, the horse's liver detoxifies these bacterial byproducts, and the body eliminates them.
Bacterial colitis occurs when abnormal or pathogenic (disease-causing) bacteria grow in the intestine and the toxins produced by them severely damage the intestinal lining. These bacteria can cause the intestinal membrane cells to secrete salts and water, or they could cause the cells to stop working altogether, which disrupts normal function.
Pathogenic bacteria can enter the body via contaminated food or water. If intestinal conditions are altered and the normal bacterial population is affected, small numbers of other types of pathogenic bacteria that normally live in the gut also might begin to grow, and colitis results. The bacteria most commonly associated with colitis in the horse are Salmonella, Campylobacter, Clostridium difficile, and Neorickettsia risticii, the causative agent for Potomac Horse Fever.
Viruses also can cause colitis in horses and in other species. Rotavirus commonly affects young foals, and parvovirus is a leading cause of colitis in dogs. Viruses commonly destroy the cells lining the intestine, which halts the absorption of intestinal fluid and produces the severe diarrhea often seen with these diseases.
Parasites can cause colitis as protozoan and other organisms physically damage the gut lining and again affect fluid resorption.
Exposure to radiation at sufficiently high dosages also will damage the delicate cells that line the intestine; colitis is a major complication of radiation poisoning.
Antibiotics and colitis
The type of colitis that is perhaps the most frustrating to horse owners and equine veterinarians is antibiotic-associated colitis. This occurs when the same drugs (antibiotics) used to help cure a sick horse cause a serious and sometimes fatal colitis. In these cases, it is believed that antibiotics kill off normal gut flora and allow pathogenic bacteria to overgrow. Excessive toxins produced by these bacteria then cause the damage that is seen clinically as colitis.
Horses with colitis show signs of abdominal pain or colic. Usually, these horses will have diarrhea, though some horses with even severe colitis might not show this condition until well into the disease process. Occasionally, in cases of severe, acute colitis that are fatal, the disease might kill too quickly for diarrhea to occur.
Affected horses could have rectal bleeding and painful straining, and they may develop a high fever (often 103¡ or higher), go off their feed, and be depressed.
Antibiotics most often associated with colitis include many that are commonly used in horses:
•Penicillin, amoxicillin, ticarcillin, and cephalosporins (Ceftiofur, Naxcel) are members of a class of antibiotics called beta-lactams. Use of these drugs has been reported to cause antibiotic-associated colitis, and package inserts for many of these products lists diarrhea as a common, adverse drug reaction and colitis as an infrequent consequence.
•Macrolide antibiotics include erythromycin and tylosin. These drugs, along with such others as oxytetracycline, have been linked to colitis.
Jonathan Foreman, D.V.M., professor of veterinary clinical medicine and a board-certified internal medicine clinician at the University of Illinois at Urbana-Champaign, is well aware of the apparent irony of this situation. "Antibiotics often associated with the development of colitis in horses are tetracycline and macrolides," said Foreman, "yet we use erythromycin [a macrolide] to treat rhodococcal diarrhea, and oxytetracycline is the drug of choice for treating Potomac Horse Fever, which is well known to cause severe diarrhea."
Foreman continued, "Oxytetracycline is used daily on the track as an antibiotic because it is broad-spectrum [has effectiveness against a wide variety of bacteria], is given in the vein [which allows for quicker activity], and is inexpensive. There seems to be little concern for its potential diarrheagenic [ability to cause diarrhea] effect."
Noah Cohen, V.M.D., Ph.D., a clinician and researcher at Texas A&M University, advised that the use of oxytetracycline and its link to colitis be put into historical perspective. At one point in time, explained Cohen, oxytetracycline was perhaps the most commonly used equine antibiotic, and the higher number of cases of associated colitis might well have been just a statistical reflection of that use. Cohen said that from an epidemiological standpoint, there is no good evidence that oxytetracycline is any more likely to cause colitis than any other antibiotic.
Stress, drugs, and colitis
In fact, some researchers question the entire idea of antibiotic-associated colitis because stress factors are commonly noted in cases that develop colitis. Changes in diet, environment, exercise routines, and transport are the most frequently listed factors. Foreman and others question if antibiotics are the initiators of the colitis seen in these cases or if stress factors could be the cause.
"Diarrhea is often attributed to the use of an antibiotic," Foreman said, "but in many cases, the horse was depressed and running a fever and then was given antibiotics. Finally, this horse developed diarrhea or colitis. But was the antibiotic the cause of the diarrhea or was the problem already beginning before the antibiotic was even given?"
Research studies are not entirely clear on this point. A recent investigation found that C. difficile was recovered from manure in 40% of horses treated with beta-lactam antibiotics for conditions other than colic, but it was not found in 22 horses with colitis that were not treated with antibiotics. These studies attempt to leap to the conclusion that less than half the horses treated with antibiotics will show the presence of pathogenic bacteria that might cause colitis (but sometimes do not). It is just not a clear enough association.
Most people involved in this area of research and clinical management agree that much more focused research needs to be done. Foreman and Cohen feel more work needs to be done to identify the risk factors at the individual horse level. Knowing these risk factors would help owners and veterinarians to identify those horses that are more likely to have an adverse drug reaction and to develop colitis with certain antibiotics.
Foreman and Cohen feel the effects of stress on individual horses and their interaction with antibiotic use should be evaluated. Much research is under way to develop tests that would allow a veterinarian to quickly and accurately identify pathogenic bacteria and their toxins present in a horse. These tests, many using new deoxyribonucleic acid (DNA) methods, would allow the veterinarian to recognize, at a much earlier stage, a horse that is at risk for developing colitis--hopefully, before the horse was administered antibiotics. These horses then could be treated appropriately, monitored more closely for development of diarrhea, and possibly treated with antibiotics, although with a lower risk of developing colitis.
The drug metronidazole (Flagyl) has been shown to have some potentially beneficial effects when used in cases of C. difficile colitis, and the antibiotic doxycycline (a form of tetracycline) seems to have a lower rate of gastrointestinal side effects. Another treatment option, Saccharomyces boulardii, which is a probiotic yeast, is being investigated for its potentially beneficial effects in treating and preventing colitis.
Clearly, these projects and others are providing horse owners and veterinarians with a better picture of the issue of antibiotic-associated colitis. But the original problem still remains: how to handle the possible side effect of colitis when deciding whether to use antibiotics in the horse.
Risk versus benefit
Many veterinarians feel such decisions ultimately come down to risk versus benefit. What are the risks of treating a condition with antibiotics versus not treating?
Equine veterinarians have been urged continually to use appropriate antibiotics only when needed in an attempt to slow the trend toward creating antibiotic-resistant bacteria. This policy should be applied in situations that might cause antibiotic-associated colitis, as well.
If the risk of infection and possible serious consequences is legitimate, antibiotics must be used. At the same time, the veterinarian should try to avoid using those antibiotics known to potentially cause colitis in already sick, febrile, or debilitated individuals, even though those same drugs frequently might be used without problem in generally healthy horses for the treatment of punctures, cuts, and other wounds.
Antibiotics have been of great benefit in the treatment of horses, and their use will undoubtedly continue. These drugs are the "good guys" in the medicine cabinet, and it is very unsettling when a case of antibiotic-associated colitis is reported.
Owners and veterinarians should be cautious when using antibiotics, and each case should be discussed carefully when the decision for or against antibiotic use is made. More research will provide more information and, hopefully, will identify risk factors that will make those decisions easier and more accurate.
source: thoroughbredtimes
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