Chapter 55: Tylosin-Responsive Diarrhea

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Tylosin-Responsive Diarrhea

Antibiotic treatment often leads to resolution of clinical gastrointestinal (GI) signs, and thus the term antibiotic-responsive diarrhea was coined for these cases. Recently trials have been published in which the antibiotic tylosin showed to be particularly effective in treating dogs with chronic or intermittent diarrhea; thus it is referred to as tylosin-responsive diarrhea (TRD).

Clinical Pharmacology

Tylosin is a macrolide, bacteriostatic antibiotic that has activity against most gram-positive and gram-negative cocci, gram-positive rods, and Mycoplasma spp. However, the gram-negative bacteria Escherichia coli and Salmonella spp. are intrinsically tylosin resistant. Tylosin is used only in veterinary medicine, and the most common indications are for treating pigs with diarrhea or poultry with chronic respiratory diseases. Tylosin also has been used as a feed additive in food animal production, and it has been shown to increase weight gain and feed efficiency, especially in pigs. The mechanisms underlying tylosin-mediated growth enhancement are debated.

Tylosin is used in a powder form for pigs and poultry. For small animals tylosin powder usually is reconstituted in capsules or mixed with the food for administration. In some European countries tylosin is also available in tablet form, which facilitates its use in dogs.

Therapeutic Use

The author’s experience with tylosin was derived first from studies in dogs having exocrine pancreatic insufficiency (EPI) and continued diarrhea after appropriate enzyme therapy. These studies found that tylosin had a favorable effect as an adjunctive therapy for dogs with EPI and diarrhea.

In recent years in Finland tylosin has become the most frequent antibiotic used in the treatment of idiopathic intermittent or chronic diarrhea in dogs. Anecdotal reports from veterinarians and dog owners reveal that many dogs with diarrhea respond quickly to tylosin treatment, generally within a few days of initiation of therapy. When tylosin is discontinued, the diarrhea often reappears within a matter of weeks or months. Some of these dogs require ongoing treatment for long periods of time. The tylosin effect in controlling diarrhea signs does not appear to diminish with time and an increased dosage is not required. No apparent tylosin-associated adverse effects have been reported.

The author’s clinical experience finds that TRD affects dogs of all breeds and ages but is observed most often in middle-aged, large-breed dogs. Signs often begin as intermittent diarrhea that becomes progressively more frequent and often persistent. Abnormal loose fecal consistency is the predominant sign. The majority of the owners describe their dogs’ feces as watery and/or of mucoid consistency, which suggests that TRD involves small- and large-bowel diarrhea. Increased frequency of borborygmus and flatulence typically also are described, and vomiting is reported occasionally during the diarrheal outbreaks.

Diagnostic evaluation of TRD cases have failed to identify an underlying cause. Routine blood parameters, fecal examinations, and diagnostic imaging studies are usually normal. When intestinal biopsies are obtained, the histologic findings are considered to be normal or to have only mild inflammatory changes.

Clinical Studies Using Tylosin for Chronic Diarrhea

Only a few studies treating diarrhea in dogs with tylosin have been published. Van Kruiningen (1976) reported more than 30 years ago that tylosin was effective in the treatment of unspecific canine diarrhea. Recently the author’s study group performed three prospective clinical trials to obtain more information on TRD (Kilpinen et al, 2011; Westermarck et al, 2005). The first study consisted of 14 adult client-owned dogs of 12 different breeds. Each dog’s diet remained unchanged throughout the study. All dogs had chronic or intermittent diarrheal signs for a period of longer than 1 year. All dogs previously had been treated successfully with tylosin for at least 6 months. Tylosin had been discontinued at least twice, but the diarrhea always recurred. These dogs then were considered to have TRD. When the study commenced, all dogs had been on tylosin for at least 1 month and were healthy and free of diarrhea. Tylosin then was discontinued, and the dogs were monitored for a period of up to 1 month to determine whether signs of diarrhea would reappear. Diarrhea reappeared in 12 of 14 dogs (85.7%) within 30 days. Tylosin, prednisone, or a probiotic treatment trial was initiated when diarrhea was present. Tylosin resulted in resolution of diarrhea in all dogs within 3 days of initiation of therapy, with most resolving within 24 hours. In contrast, prednisone did not completely resolve diarrheal signs, and the probiotic Lactobacillus rhamnosus GG did not prevent the relapse of diarrhea in any of the dogs.

In a second study seven beagles with chronic diarrhea for at least 1 month were identified from an experimental dog colony. Treatment trials of antibiotics, prednisone, and diet were applied. Tylosin was administered for 10 days, and during that time the feces became significantly firmer, although they remained unacceptably loose. When the treatment was discontinued, diarrhea reappeared within 3 weeks. Next treatment trials with other antibiotics (metronidazole, trimethoprim-sulfadiazine, or doxycycline) and prednisone had almost no effect on fecal consistency in these dogs. The diet was then changed for a 10-day period from a highly digestible moist pet food to a dry food developed for normal adult dogs. The feces again became significantly firmer, although the fecal consistency remained loose in some dogs. The dry food feeding period was then extended to 3 months, and the fecal consistency continued to fluctuate from ideal to diarrhea. Because the consistency was not satisfactory on diet alone, tylosin was added to the therapy for 10 days. The fecal consistency became normal and remained so throughout the entire 3-month follow-up time of this study. The study demonstrated that, in this group of experimental dogs having chronic diarrhea, the fecal consistency became significantly firmer using tylosin in conjunction with dietary modification. Neither treatment alone was sufficient to obtain ideal fecal consistency, but when the dogs were treated simultaneously with both regimens, ideal fecal consistency was achieved and maintained. The study suggests that tylosin and feeding regimens had a synergic effect.

In the author’s latest placebo-controlled randomized, double-blinded, prospective clinical trial on dogs with suspected TRD the effect of tylosin on fecal consistency is assessed compared with a placebo treatment. In addition, the author wanted to determine whether tylosin in dogs with recurrent diarrhea is as effective as empiric studies and anecdotal reports suggest. The proportion of dogs with normal fecal consistency at the end of the 7-day treatment period was 85% in the tylosin group and 29% in the placebo group. These findings indicated that tylosin was significantly more effective than the placebo in treating recurrent diarrhea in dogs.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Chapter 55: Tylosin-Responsive Diarrhea

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