Overview

• Defined as antibiotic-responsive diarrhea without an identifiable underlying etiology.
• Antibiotic-responsive diarrhea was previously termed idiopathic (primary) small intestinal bacterial overgrowth (SIBO). This term is not used anymore as it was based on quantitative culture of bacteria in the upper GI tract which could not be confirmed by newer PCR-based methods. Secondary SIBO is a result of concurrent gastrointestinal diseases (e.g., exocrine pancreatic insufficiency).
• Current theories center on the possibility of immune dysregulation, possibly associated with abnormal CD4+ T-cells, IgA plasma cells, cytokine expression, and, in German shepherd dogs, mutations in pattern recognition receptors.

Signalment

Signs

Causes & Risk Factors

• Genetic risk factors of mutations in pattern recognition genes (TLR4 and TLR5) have been associated with the disease
• Certain enteropathogenic bacteria (Clostridium perfringens, E. coli, and Lawsonia intracellularis) have been suspected but not proven to be etiologic agents.

Differential Diagnosis

• Secondary SIBO
• EPI
• Parasitic infection
• IBD (including food-responsive diarrhea)
• Neoplasia

CBC/Biochemistry/Urinalysis

• Typically normal.
• Hypoalbuminemia is an uncommon finding.

Other Laboratory Tests

• Fecal examination for parasites should be performed.
• Serum cobalamin levels may be low and folate levels may be increased or decreased.
• Serum TLI levels (measured to rule out EPI) are normal.

Imaging

Routine abdominal imaging (radiographs and ultrasound) should be performed to rule out other causes for diarrhea. Results of these tests are unremarkable in cases of ARD.

Diagnostic Procedures

• There is no definitive test for the diagnosis of ARD other than resolution of gastrointestinal signs following antibiotic administration.
• Diagnosis depends upon ruling out all other causes for chronic diarrhea (especially food-responsive diarrhea) and a clinical response to an appropriate course of antibiotic therapy.

Drug(s)

• Several options for antibiotics are available:
  • Tylosin (5–10 mg/kg PO q24h); metronidazole (10–20 mg/kg PO q12h); oxytetracycline (10–20 mg/kg PO q8h).
• In some cases, combination therapy may be necessary.
  • Antibiotic therapy should be administered for 4–6 weeks.
• If serum cobalamin levels are decreased, cobalamin supplementation should be pursued. Dogs <15 kg body weight: 500 µg parenteral cobalamin; dogs >15 kg body weight: up to 1,500 µg parenteral cobalamin. Doses are given as subcutaneous injections once weekly for 6 weeks, then once every other week for 6 weeks. Serum cobalamin levels should be reassessed at the end of therapy. Limited information is available regarding the effectiveness of oral cobalamin supplementation.

Contraindications/Possible Interactions

• Oxytetracycline may cause staining of tooth enamel. Doses should be decreased in animals with hepatic or renal insufficiency. Oxytetracycline has been associated with a high incidence of bacterial transfer of resistance genes.
• Metronidazole undergoes extensive hepatic metabolism; dosages should be reduced in animals with hepatic insufficiency.

Abbreviations

• ARD = antibiotic responsive diarrhea
• EPI = exocrine pancreatic insufficiency
• IBD = inflammatory bowel disease
• SIBO = small intestinal bacterial overgrowth
• TLI = trypsin like immunoreactivity