Evaluation of Metronidazole With and Without Enterococcus Faecium SF68 in Shelter Dogs With Diarrhea

Diarrhea is common in shelter dogs and nonspecific therapies like therapeutic diets, probiotics, and drugs with activity against Giardia spp. or enteric bacteria are commonly prescribed empirically. All dogs in this study were administered metronidazole, fed a standardized diet, and randomized to either receive a commercially available probiotic (Purina^® Pro Plan^® Veterinary Diets; FortiFlora^® Probiotic Supplement, FortiFlora, Nestle Purina PetCare, St Louis, MO) or a placebo which was the commercial product without the probiotic for 7 days. A fecal score was assigned to each stool passed during the study by masked individuals. Fecal samples were evaluated for select enteric agents including nematodes, Giardia spp., Cryptosporidium spp., and Clostridium perfringens enterotoxin before and at the end of the treatment period. There were no differences between groups in regard to parasite prevalence. By day 7, a normal stool (<5) was detected in 37.5% of the dogs administered metronidazole and 68.8% of the dogs administered dual therapy, but the result was not significant (P = .1556). The percentages of days with normal stools were significantly higher (P = .0496) for dogs administered dual therapy 65.6%) when compared to those administered metronidazole alone (46.9%). Giardia cysts were eliminated and diarrhea resolved in both dogs that were infected in the SF68 group. In contrast, of the 7 Giardia positive dogs in the placebo group, 6 (85.7%) were still positive for Giardia cysts on day 7, and 4 of those dogs still had diarrhea on day 7. Addition of SF68 to this protocol of metronidazole and a standardized diet appeared to enhance clinical responses in shelter dogs with diarrhea.

Introduction

Diarrhea is extremely common in dogs housed in animal shelters and is often a consequence of parasitic agents, stress, and dietary changes. This problem is significant for many reasons including animal discomfort, delayed adoption, and even euthanasia owing to financial strain on shelter resources. In shelters, a complete workup to assess for causes of diarrhea is often not performed because of expense. Thus, many diarrhea cases are classified as nonspecific and are treated empirically.

A variety of antibiotics have been prescribed for treatment of nonspecific diarrhea in dogs including metronidazole, tylosin, and amoxicillin. Metronidazole has multiple advantages for treating diarrheal disorders with one being its spectrum against Giardia species.¹ Metronidazole is also effective in treating Clostridium perfringens-associated diarrhea while altering other aerobic and anaerobic populations of bacteria within the small intestine.¹ Lastly, metronidazole has both immunomodulatory and anti-inflammatory properties mediated through reduction of CD4+ lymphocytes and decreased levels of TNF and INF-γ within the gastrointestinal (GI) tract in a murine model.² It is believed that these or similar effects may also occur in dogs.

Feeding a standardized diet and administering metronidazole often resolves diarrhea in shelter dogs, but there are select animals that require additional therapies. Finding a combination of treatments that could successfully treat or increase the speed to resolution of nonspecific diarrhea would be extremely beneficial to shelters because of decreased time to adoption and decreased shelter staff workload.

Probiotics, defined as microorganisms that when administered in adequate amounts can confer a positive health effect on the host, are often used in the management of nonspecific diarrhea.³ Some probiotics in humans have well-established effects including prevention and reduction of rotavirus-induced or antibiotic-associated diarrhea, and prevention and alleviation of nonspecific GI issues.³ Given these findings in human medicine, probiotics may have the potential to lessen diarrhea in shelter animals.

Enterococcus faecium strain SF68² (SF68) is an orally administered probiotic that when administered to dogs and cats has many proven beneficial effects including maintaining fecal microbiota diversity, increasing serum and fecal IgA concentrations, and having potential immune modulating activity.4, 5, 6 The safety of exogenous administration of SF68 has been confirmed in both human and animals. In addition to its low pathogenicity and absence of virulence factors, SF68 does not permanently colonize the GI tract even after prolonged administration.⁷ In a recent study of shelter cats fed the commercial product containing SF68 (Purina^® Pro Plan^® Veterinary Diets; FortiFlora^® Probiotic Supplement)² or the product without the probiotic (placebo), the percentage of cats with diarrhea ≥2 days were significantly lower in the probiotic group when compared to the controls fed the placebo.⁸ SF68 was studied as a targeted therapy for Giardia in a rodent model and was shown to decrease shedding of the organism when administered before infection.⁹ However, the results were not duplicated in 1 dog study using naturally infected animals that were infected before the administration of the probiotic.¹⁰

Very little is known regarding the clinical effects of combining probiotics with antibiotics when treating GI abnormalities in dogs. The following clinical study was proposed to explore another potential treatment option in dogs that commonly experience diarrhea in shelters thereby hindering their adoption. Thus, the first objective of this study was to confirm whether SF68 was resistant to metronidazole to evaluate for the potential for concurrent administration to dogs with diarrhea. The second objective was to determine whether administration of metronidazole with SF68 was superior to metronidazole alone in resolving nonspecific diarrhea in shelter dogs. The third objective was to gather pilot data concerning the effect on targeted infectious agents that would likely respond to metronidazole with or without SF68, in particular Giardia spp. and C. perfringens.