How to manage feline chronic diarrhea, Part II: Treatment
Chronic diarrhea is best managed with targeted therapy based on a specific diagnosis. However, symptomatic or nonspecific therapies are often initially considered for patients that seem to be feeling well otherwise and when preliminary testing fails to establish a definitive diagnosis. Specific and symptomatic medical therapy may be used together to achieve greater success.
In cats with diarrhea caused by Giardia, Cystoisospora, or Tritrichomonas species, an antiparasitic, antiprotozoal, or antimicrobial agent is indicated alone or in combination.
Fenbendazole is a benzimidazole antiparasitic that appears to be an effective option in cats with giardiasis (Table 1), without the hematologic complications associated with albendazole.1 Concern has been expressed regarding the efficacy of fenbendazole against Giardia species in certain cases.2 Although both fenbendazole and metronidazole are recommended as sole therapies for treating giardiasis, the Companion Animal Parasite Council also advocates the combination of fenbendazole at 50 mg/kg once daily with metronidazole at 25 mg/kg twice daily for 5 days.1 Fenbendazole appears to have a wide safety margin but is not FDA-approved for use in cats.3
Metronidazole reduced cyst shedding in cats experimentally infected with Giardia lamblia.4 The maximum daily dose should not exceed 50 mg/kg (Table 1) since this has been associated with neurotoxicosis in cats.5 Signs of toxicosis include lethargy, vomiting, ataxia, vocalization, and seizures. These signs usually resolve within five to seven days of discontinuing the drug. Cats find metronidazole unpalatable and may salivate profusely after administration of broken tablets. This unpalatability can be managed by compounding the drug into capsules of smaller doses or placing partial tablets in gelatin capsules for administration.
Toltrazuril and ponazuril
Recent limited studies have examined the efficacy of toltrazuril for treating coccidiosis in kittens and puppies.6 Toltrazuril is only available in the United States through compounding pharmacies, and quality control may be a concern. An effective toltrazuril dose is 30 mg/kg administered orally one time, or 15 mg/kg every 24 hours for three days; patients can be retreated after 10 days if necessary.6
Ponazuril (Marquis—Bayer Animal Health) is an equine antiprotozoal paste with efficacy against canine Cystoisospora species.7 It is not FDA-approved for use in companion animals but may be administered to cats as a single 30-mg/kg dose if standard anticoccidial therapy fails to clear oocysts from feces and the diarrhea persists.8 Marquis contains 150 mg ponazuril per gram of paste. Dilution of one syringe (120 ml of paste) in 21 ml of water results in a 135-mg/ml solution. This solution should be protected from light and shaken well before use.
Tritrichomonas foetus has recently been recognized as a cause of chronic large bowel diarrhea in young cats. Different antibiotics have been used to treat T. foetus infection, but ronidazole remains the most effective agent at eradicating the organism and preventing relapse of infection.9 Ronidazole is a nitroimidazole antimicrobial similar to metronidazole. It is not FDA-approved for use in companion animals and must be acquired from a compounding pharmacy.
It is important that the dose be calculated for each cat since neurotoxicosis has been reported and seems to be more likely if the recommended dose is exceeded (Table 1).10 Signs of toxicosis include incoordination, anorexia, ataxia, and seizures. These signs usually resolve once the drug is discontinued but can last up to four weeks. Because of the risk of neurotoxicosis, treatment with ronidazole should not be considered without confirmation of T. foetus infection.
Additional measures: Environmental control
Treatment of protozoal diarrhea is greatly enhanced by environmental control because this minimizes the chance of reinfection. Prompt removal of feces from the litter box is essential since protozoal cysts may otherwise become scattered in the home. Disinfection with quaternary ammonium compounds (e.g. Roccal D—Pfizer Animal Health) or steam cleaning eliminates Giardia species cysts and Cystoisospora species oocysts as long as adequate drying time is allowed for desiccation. Bathing affected animals during and after therapy is also helpful because it removes cysts and oocysts carried on the fur.
Antimicrobials can be used to treat cats with Clostridium or Campylobacter species-associated diarrhea, chronic idiopathic diarrhea, or inflammatory bowel disease (IBD).
Metronidazole is a nitroimidazole antimicrobial with activity against anaerobic bacteria and some protozoal species. It may also exert some immunomodulatory effects and anti-inflammatory properties. Metronidazole can be used to treat Clostridium difficile-associated diarrhea, chronic idiopathic diarrhea, and IBD11 (Table 2).12
Clostridium perfringens has been associated with chronic diarrhea in dogs and cats. Although the pathogenesis of C. perfringens enterotoxicosis (CPE) has not been determined, the organism is typically sensitive to tylosin administration.13 Tylosin, a macrolide antibiotic, is available as a powdered formulation containing about 2,600 mg of active agent per teaspoon (Tylan Soluble—Elanco); it may help to mix the powder with confectioner's sugar in a ratio of 1:1 to achieve a more useable concentration. The resulting formulation would then contain about 1,300 mg of active agent per teaspoon. Tylosin can be given with meals (Table 2),14 but cats may refuse the powder even when mixed with appetizing or strong-smelling foods, and it may be easier to administer the drug in a capsule. In addition to its antibacterial properties, tylosin appears to have some immunomodulatory effects, making it a possible adjunctive treatment for IBD.
Management of chronic diarrhea is usually not complete without considering dietary intervention. This may be beneficial either alone or in conjunction with primary treatment of the underlying disease. A range of diets is available for cats with chronic diarrhea and includes highly digestible, high-fiber, and exclusion diets.
Highly digestible diets
An ideal highly digestible diet should contain a single protein source, no allergenic additives or flavorings, and nutrients with protein digestibility > 87% and carbohydrate digestibility > 90%.16 High digestibility minimizes intestinal bacterial metabolism and ensures ease of nutrient assimilation when digestive function is poor. It also results in less fecal volume in many cases. These diets can be used for a variety of gastrointestinal (GI) diseases but have resulted in improved fecal scores in cats with chronic, nonspecific diarrhea.
High-fiber diets may be helpful in cats with large bowel diarrhea. Insoluble fibers increase fecal bulk, improve intestinal motility, and bind nonabsorbed fluid in the intestinal lumen. Soluble fibers decrease fecal bulk, bind nonabsorbed fluid into gels, and increase the concentrations of beneficial bacteria. Soluble fibers are fermented by intestinal bacteria into short-chain fatty acids, which are the preferred energy source for colonocytes. They also decrease intestinal intraluminal pH, thereby inhibiting opportunistic pathogens such as Clostridium and Salmonella species. Most high-fiber diets contain both soluble and insoluble forms to provide the benefits of both.
Elimination diets are indicated if food allergy or food intolerance is suspected. Many elimination diets are available that contain either hydrolyzed proteins or novel proteins along with novel carbohydrate sources. The term hydrolyzed refers to proteins that have been cleaved into small fragments, thereby minimizing antigenic stimulation. Elimination diets can be prepared by owners at home, but they must be nutritionally balanced to prevent vitamin and mineral deficiencies if long-term use is planned.
When selecting an elimination diet, it is important to choose a protein source to which the patient has not been previously exposed since prior sensitization may have occurred. Elimination diet trials should last at least eight to 12 weeks. Owner compliance is often a limiting factor because strict adherence to the therapeutic diet is necessary to maximize its efficacy. To fully assess the therapeutic success of an elimination diet, the patient should be challenged with the original diet to verify return of clinical signs. Often this is not possible because owners are reluctant to risk a relapse in a well-controlled patient.
IMMUNOSUPPRESSIVE DRUG THERAPY
Immunosuppressive drugs can be used effectively in cats with chronic diarrhea due to IBD, especially when dietary therapy has not improved or completely resolved clinical signs. Immunosuppressive drug therapy is also indicated in the treatment of intestinal lymphoma along with adjunctive therapy.
IBD, the persistent inflammation of the GI tract without any identifiable pathogen or trigger, is one of the most common causes of chronic diarrhea in cats. Corticosteroids remain the cornerstone of treatment in cats with histologic evidence of otherwise unexplained intestinal inflammation (usually lymphoplasmacytic or eosinophilic). Prednisolone is preferred to prednisone because of increased bioavailability in cats.
If prednisolone is poorly tolerated, budesonide can be used as an alternative. This locally acting corticosteroid undergoes extensive first-pass metabolism in the liver, so systemic exposure is theoretically minimized. Budesonide has not been thoroughly evaluated in cats, but it produces fewer unwanted side effects in dogs when compared with prednisone.18 However, long-term use is still associated with suppression of the pituitary-adrenal axis, indicating some generalized effects. The recommended dose is 1 mg/cat orally every 24 hours (Table 3). Budesonide is expensive and must be compounded before it can be used in cats.
In some patients with refractory IBD or intestinal small cell lymphoma, chlorambucil should be considered.19 This alkylating, antineoplastic, and immunosuppressive agent may be used in conjunction with prednisolone in these cases. Various dose schedules have been described; we usually recommend 2 mg/cat orally every 48 hours (Table 3). It may cause vomiting or a decrease in appetite in some individuals, and the dose or frequency of administration may need to be modified if these adverse effects occur. The most serious side effect of chlorambucil is myelosuppression, so it is important to perform a complete blood count every month or two.
Cyclosporine is a T-cell lymphocyte suppressor with demonstrated efficacy in steroid-refractory IBD in dogs.20 It is occasionally used to treat dermatologic conditions in cats, but its use in cats with IBD has not been reported. The recommended dose for cats is 1-4 mg/kg orally every 12 to 24 hours (Table 3).21 Cyclosporine can cause vomiting or anorexia in some patients.
Azathioprine is a purine antagonist antimetabolite with potent immunosuppressive properties. It is routinely used for refractory IBD in dogs. However, it is not recommended for use in cats because of the potential for fatal bone marrow toxicosis and difficulties with accurate dosing.
Adjunctive therapies in cats with chronic diarrhea include cobalamin, pancreatic enzymes, prebiotics, probiotics, GI protectants, and motility modifiers and may be needed in patients with the specific conditions described below or in patients with nonspecific diarrhea in which conservative therapy is preferred.
Feline EPI is a rare but important cause of chronic, voluminous diarrhea accompanied by weight loss in cats. The cornerstone of EPI management is pancreatic enzyme replacement. Powdered pancreatic enzyme extract (Pancrezyme—Virbac) should be mixed with food before feeding at a dose of 1/4 to 3/4 tsp per meal. Alternatively, chopped cow or pig pancreas can be added to the food at a dose of 1 to 3 oz per meal. Fresh pancreas is inexpensive and can be obtained at slaughterhouse facilities and occasionally at local grocery stores by special order. It can be frozen for up to three months while maintaining enzyme activity. Any cat with EPI should also receive parenteral cobalamin supplementation (Table 4).
Prebiotics are nondigestible ingredients that promote specific changes in GI microflora, which are presumed to confer various health benefits on the host.25 Many prebiotics are moderately fermentable fibers such as beet pulp, psyllium, or soy and appear to favor beneficial colonic bacteria. Psyllium fiber supplements (Vetasyl—Virbac) are often used for their laxative properties but may also help improve fecal consistency in cats with chronic large bowel diarrhea. The recommended dose is 1 tsp mixed with food once or twice daily. Patients receiving psyllium should have access to water at all times to prevent fecal impaction and intestinal obstruction. Canned pumpkin is an alternative fiber source for cats and can be useful in managing patients with colitis.
Fructooligosaccharides (FOS) are long chains of fructose molecules and are found in many different plants. FOS selectively feed Bifidobacterium species, Lactobacillus acidophilus, and other lactobacilli species. Supplementation with FOS is thought to favor the growth of beneficial bacteria and improve intestinal health and function.26 To date, no studies have been performed in cats with chronic diarrhea that demonstrate positive response to treatment.
Probiotics are live microorganisms administered in amounts that confer health benefits on the host. They are reported to play a role in improving immune response, replenishing normal GI microflora, and hastening the resolution of diarrhea. They must be viable and metabolically active with the GI tract of the host to be beneficial. Because probiotics are nutritional supplements, they are not regulated by the FDA, and manufacturers are not required to show efficacy or viability of product contents.
When commercial probiotics were evaluated, the contents of many products did not match the organisms listed on the package.27 Only recommend products from reputable companies with labels describing the strain and number of live organisms present. Many veterinary probiotics are available, each with various species and strains of bacteria, and an individual patient may show a positive response to one formulation but not another. However, little independent data support the use of probiotic products in cats with clinical disease, and probiotics should not be used in place of standard therapeutics in cats with infectious diarrhea.
Oral GI protectants and adsorbents
Oral protectants and adsorbents work locally within the GI tract either by coating inflamed mucosa with a protective layer or by binding bacteria, toxins, and digestive juices and, thus, preventing mucosal damage and systemic absorption. Adsorbents lack specificity and may prevent drug absorption as well. The most commonly used drugs in this category are bismuth subsalicylate (Pepto-Bismol—Procter & Gamble) and kaolin-pectin (Kaopectate—Pharmacia).
The old formulation of Kaopectate contained only kaolin and pectin, while later formulations contain attapulgite. These substances change the consistency of the feces but have no effect on fluid or electrolyte loss. All three of these substances are safe for cats as they are not absorbed into the bloodstream. Recently, Kaopectate was reformulated to contain bismuth subsalicylate. Bismuth subsalicylate has antibacterial, antienterotoxin, and anti-inflammatory properties. Exercise caution when using this drug because salicylate compounds are slowly eliminated in cats if systemic absorption occurs. Bismuth subsalicylate can be used in cats at a dose of 0.5 to 1 ml/kg orally every 12 hours for no longer than two or three days.28 Cats strongly resist the taste of this medication, and its use may produce green-black stools resembling melena.
Motility modifiers increase GI transit time, thereby allowing more water reabsorption from the luminal contents. These drugs may be indicated if fluid losses are high, fluid replacement is not sufficient to maintain adequate hydration, and the diarrhea is intractable. Motility modifiers are contraindicated in patients with infectious diarrhea because they may increase absorption of bacterial toxins.
Centrine (Pfizer Animal Health) is an antispasmodic and anticholinergic agent whose active ingredient is aminopentamide hydrogen sulfate. It is commonly used to treat diarrhea, abdominal visceral spasm, vomiting, and gastritis in dogs and cats. The dose for cats is 0.1 mg orally every eight to 12 hours.29 Adverse effects include dry eyes and mouth, inability to urinate, difficulty swallowing, vomiting, constipation, sedation or excitement, staggering, seizures, enlarged pupils, and abnormal heart rhythms; death may also occur.29
Cats can also be given diphenoxylate hydrochloride30 (1.25 mg orally every 12 hours) or loperamide hydrochloride (0.04 to 0.06 mg/kg orally every 12 hours).31 However, we think that these drugs are rarely appropriate in feline patients and can cause adverse reactions, including respiratory depression and excitatory behavior.
Chronic diarrhea doesn't resolve overnight. Even with a specific diagnosis, diarrhea may not resolve with targeted pharmacologic therapy alone. Dietary, prebiotic, and probiotic therapy are important complementary options and may serve as sole therapy in some patients with nonspecific disease. A multimodal approach often produces the best chance for clinical improvement.
Sally Purcell, DVM
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