Antimicrobials are often used as a treatment for acute diarrhoea (AD) in dogs. However, evidence supporting such antimicrobial use is limited and inappropriate antimicrobial use may worsen microbial resistance. Evaluating the reported causes of acute diarrhoea may help improve antimicrobial stewardship.

Acute Diarrhoea in Dogs

Acute diarrhoea (less than 7 days duration) is a frequent presenting complaint. Emergency and critical care veterinarians commonly see canine parvoviral (CPV) enteritis and acute haemorrhagic diarrhoea syndrome (AHDS). With clinical signs including severe dehydration, hypovolaemic shock, and ongoing fluid losses, these cases typically require aggressive inpatient medical management. Whilst there is a general consensus for the use of broad-spectrum antimicrobial use in dogs with CPV enteritis, no such consensus exists for AHDS.

Are enteric microorganisms really causing acute diarrhea?

The numerous causes of acute diarrhea in dogs are summarised elsewhere. Infectious causes, the most obvious justification for antimicrobial use, include Clostridia, Campylobacter, Salmonella, E. coli, Giardia, CPV, enteric coronavirus, rotavirus, and circovirus. Aside from CPV, studies investigating these microorganisms reveal the difficulty in separating pathogens from non-pathogens. These microorganisms are frequently detected in healthy, non-diarrhoeic dogs. Thus we should use the label ‘pathogen’ cautiously. Rather than a single causative microorganism, some authors promote a state of dysbiosis—a deleterious disruption to the normal gut microbiome—as a major contributor to disease. In contrast, a ‘healthy’ microbiome may negate the effects of any potential pathogens in healthy dogs.

AHDS and C. perfringens

Clostridium perfringens is a gram-positive commensal anaerobe of the canine gastrointestinal tract and an established cause of diarrhoea in humans. However, similar prevalence is reported in dogs with AD and in healthy dogs. Appropriate diagnostic tests must differentiate non-pathogenic from pathogenic subtypes, i.e., those producing enterotoxins associated with diarrhoea. Previously, C. perfringens enterotoxin was the main suspect in infectious AD in dogs. However, ELISA testing for C. perfringens enterotoxin is not widely available and many readily-available PCR tests detect other non-pathogenic enterotoxins (e.g., C. perfringens alpha toxin). Furthermore, many of these enterotoxins (or encoding genes) are found in healthy dogs. A growing body of evidence points to C. perfringens necrotising enterotoxins NetE and NetF as major contributors to AHDS in dogs. Two studies detected a higher prevalence of NetF-encoding genes in dogs with AHDS compared to dogs with non-AHDS gastrointestinal disease and healthy dogs.

Salmonella spp.

Salmonella spp. are gram-negative facultative anaerobes with an unclear role in acute gastrointestinal illness in dogs given its comparable prevalence in healthy dogs and dogs with diarrhoea. Regardless of disease status, Salmonella spp. have strong associations with raw food diets. Thus, its main relevance may be the risk of transmission to immunocompromised humans and pets due to shedding from dogs fed raw meat diets.

Campylobacter spp.

Campylobacter spp. are gram-negative zoonotic aerobes. Contamination from contact with dogs was the second most common cause of campylobacteriosis in humans in a Swedish epidemiology study. Once again, the prevalence amongst healthy and diarrhoeic dogs is variable and available data fail to support a clear pathogenic role, although some studies suggest puppies are an at-risk population.

Giardia spp.

Giardia spp. are protozoa considered epizootic in most regions and is the leading waterborne cause of diarrhoea in humans in the U.S. Again, many prevalence studies do not support a definitive role in AD. A Japanese study reported a healthy-dog prevalence (44.4%) more than double that of diarrhoeic dogs (20.6%). Zoonotic potential is also a key concern.

Other

The role of Escherichia coli in AD is unclear: a laboratory study found only extra-enteric strains of E. coli in diarrhoeic dogs. Similarly, Clostridium difficile has a comparable prevalence in healthy and diarrhoeic dogs. Detection of enterotoxins A, B, or their genes, may increase suspicion for clostridiosis, especially if no other infectious or non-infectious causes are found. Canine enteric coronavirus and canine adenovirus are established causes of AD, but prevalence has dramatically decreased with widespread vaccination among companion dog populations. Recent advances, notably with molecular diagnostics, have led to the discovery of other potential enteric pathogens such as Providencia alcalifaciens.

The recurring theme is the lack of evidence linking microorganism detection with causation in dogs with AD. Detection of these enteric microorganisms may reflect normal gastrointestinal flora or may be a marker of dysbiosis.

Treatment

Numerous prospective clinical trials demonstrate a good response to supportive medical management (correction of intra- and extravascular fluid deficits, addressing ongoing fluid losses, and symptomatic treatment) of dogs with AD. Specific underlying causes such as dietary intolerances, chronic inflammatory conditions, helminthiasis, or diseases of other abdominal organs (pancreas, liver, kidney) should be addressed. Despite such evidence, survey studies report antimicrobial usage in 31% to 71% of dogs with AD. Amoxicillin, alone or potentiated, and metronidazole are most frequently prescribed.

So why are antimicrobials being used for acute diarrhoea in dogs?

Treating a confirmed or suspected infectious cause is the primary reason for antimicrobial use in these cases. However, there are two main concerns with antimicrobial use for potentially infectious causes of AHDS or AD. First, it is not clear that antimicrobial use improves outcomes or even the clinical course of the disease. Second, detection of a microorganism does not always confirm an infectious cause.

Although AHDS may have an infectious aetiology, several clinical trials have failed to show an improvement in outcome with antimicrobial treatment. A randomised clinical trial (RCT) comparing label-dose amoxicillin-clavulanic acid to placebo in 60 dogs with AHDS found no difference in clinical progression. All dogs improved within 48 hours, including the placebo group receiving standard care only. Similar results were found in dogs with AHDS given amoxicillin-clavulanic acid either with or without metronidazole. Metronidazole use has been justified for its anti-inflammatory, antidiarrheal, antiprotozoal effects, and anaerobic coverage. However, there is no evidence metronidazole has a meaningful anti-inflammatory effect in dogs with AD.

And why shouldn’t antimicrobials be used in AD?

First, we must use antimicrobials responsibly to limit antimicrobial resistance. This requires considered selection of patients, selection of appropriate antimicrobials when indicated, evidence-based protocols (dose, duration, route), and regular review of these factors.

Second, antimicrobials can significantly disrupt the enteric microbiome, with potential short- and long-term adverse effects. This can result in greater numbers of toxin-producing species, resistant microorganisms, and long-term dysbiosis. Fourteen days of metronidazole treatment in healthy dogs resulted in adverse changes to the faecal microbiome—including decreased diversity and reductions in ‘beneficial’ microorganisms. Given we know AD already causes major disruptions to the microbiome with potential for long-term consequences, further alterations to the microbiome by antimicrobial use are clearly undesirable.

What are the indications for antimicrobial use?

For AHDS, antimicrobials should be reserved for dogs exhibiting signs of sepsis, i.e., clinical signs fulfilling SIRS criteria and evidence of organ dysfunction. Given the low specificity of these criteria, I recommend reserving antimicrobial use for dogs fulfilling these criteria and deteriorating despite appropriate aggressive medical therapy (restoration of intra- and extravascular fluid volumes and medical management of clinical signs).

For Salmonella, Campylobacter, Giardia, and other potentially infectious microorganisms, the question always arises—does detection equal causation? Given the challenges of making a definitive diagnosis, and with evidence that the majority of these cases will have self-limiting diarrhoea, the same approach is recommended. Antimicrobials should be reserved where sepsis is suspected and the dog is deteriorating despite appropriate therapy. Puppies may have a greater need for antimicrobial therapy, given their higher susceptibility to giardiasis and to more severe illness. An additional important consideration is the zoonotic potential. Understandably this provides greater impetus to start antimicrobial therapy with the intention of reducing or eliminating zoonotic risk, especially if there are immunocompromised human or animal companions. This should be evaluated on a case-by-case basis.

What other treatments are available?

There is a growing body of evidence exploring pre-, pro-, and synbiotic (combining pre- and probiotics) use in AD, with mixed results. A small RCT in AHDS dogs showed no difference in time to resolution of diarrhoea and no difference in dysbiosis, as indicated by quantifying eight bacterial groups. More research is required.

Faecal microbial transplants may also have a role in treating AD in dogs. A small controlled trial in eight AHDS dogs showed improved microbiome diversity post-transplantation, but no difference in outcome compared with the control group.

Antimicrobial Stewardship Programs

Improving antimicrobial stewardship may require more than just case-by-case changes to antimicrobial use. Large-scale stewardship programs in human medicine have demonstrated their worth. Recently, a national veterinary program in Switzerland reduced overall antimicrobial prescription and increased adherence to usage guidelines, including in dogs with AD/AHDS.

Conclusion

Current evidence shows the majority of AD cases, including AHDS, do not require antimicrobial therapy even when potential enteric pathogens are detected. National or multinational programs may help our profession improve antimicrobial stewardship.

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