Acute diarrhea is one of the most common reasons for pets to present to the veterinarian for care; It’s a non-specific sign of disease and there are many potential causes. Primary GI causes include dietary indiscretion, intestinal parasitism, infection (viral, bacterial, fungal), and non-specific gastroenteritis. Diarrhea can also be seen in association with other diseases (e.g. pancreatitis, kidney disease, liver disease, Addison’s disease, etc.). Two of the most common reasons remain dietary indiscretion and non-specific gastroenteritis, and management of these causes of diarrhea is the focus of this article.
Antibiotics have long been a reflexive part of managing acute diarrhea in dogs and cats, with metronidazole one of the most commonly prescribed. One retrospective study of primary care veterinarians found that systemic antibiotics were prescribed in nearly 50% of acute cases of diarrhea in dogs whereas only 3% of patients had diagnostic testing of any type to support antibiotic use.1 Clinically, we often observe improvement in stool quality when metronidazole is prescribed, but there are important questions to consider:
- Is the animal better because of the antibiotic (or in spite of it)?
- What is this medication actually doing inside the gut?
- Is it truly necessary?
The answers to those questions matter because antibiotic resistance has become a significant concern in both human and animal health. Antimicrobial stewardship and principles around the judicious use of antibiotics are becoming discussed more and more. It is incumbent on everyone to re-examine the role of antibiotics in managing a variety of diseases - particularly when outcomes may be the same without them. Acute diarrhea is one condition that’s been studied fairly extensively. Furthermore, though we've long known that antibiotics lead to alterations and shifts in bacterial populations of the gut, we continue to learn a lot about the gut microbiome and its importance in many aspects of health – some even refer to it as an organ.
Metronidazole is one antibiotic that is indicated for treating anaerobic bacterial and some protozoal infections (e.g. Giardia). The drug is a known carcinogen in laboratory animals – especially when given at high doses for prolonged periods of time. As such, the FDA has issued a black box warning for this drug and, in humans, only recommends its use for clearly indicated conditions and with caution if given repeatedly or used long-term.2 Generally speaking, any drug that confers benefits comes with possible side effects. Metronidazole is known to potentially cause lethargy, decreased appetite, vomiting, soft stools, and neurologic side effects. More importantly, metronidazole has side effects that may not be outwardly apparent. Antibiotics (including metronidazole) affect the gut microbiome, even in healthy dogs.3
Studies have shown that dogs treated with metronidazole experienced a significant shift (for the worse) in the dysbiosis index (a measure of beneficial bacteria in the GI tract), a reduction in microbial richness and diversity, and a decrease in secondary bile acids (they play a key role in maintaining gut barrier integrity and preventing overgrowth of pathogenic bacteria). Perhaps most concerning is that these effects are not short-lived. Even four weeks after discontinuing metronidazole, many dogs may still have evidence of persistent dysbiosis and secondary bile acid levels that do not fully recover.4,5 Data from one study showed a dramatic shift in microbial populations when metronidazole was initiated and that only partially normalized weeks after the drug was stopped.4
This knowledge has prompted the reconsideration of treatment approaches for patients with acute diarrhea. We know that giving antibiotics and disrupting the microbiome may have consequences that extend well beyond a single episode of diarrhea. In other words, while diarrhea may improve clinically, the microbiome may remain disrupted long after treatment with metronidazole ends. The bigger concern ties to the fact that the intestinal microbiome plays a critical role in health far beyond digestion; It contributes to a variety of important mechanisms including immune system regulation, weight and metabolism, behavior and the function of other organs (e.g. brain, kidney).
So, what are other evidence-based options for managing patients with acute diarrhea?
- Watchful waiting or doing nothing. While we always want to do something of a supportive nature for our patients, one study of dogs with acute diarrhea showed that the time to resolution was essentially the same whether dogs received placebo or a course of metronidazole.6
- Manipulate the diet and add fiber. Feeding a bland or highly digestible diet and supplementing with fiber can be very helpful. Fiber (a prebiotic) promotes health of cells in the colon and also modulates microbial populations in the gut. In a study of 59 dogs with acute colitis, dogs given a placebo and fed either a highly digestible diet or a fiber-enhanced highly digestible diet had faster resolution of diarrhea compared to those fed a highly digestible diet and treated with metronidazole.7
- Probiotics can provide equal or superior results (time to resolution) as compared to metronidazole when given to dogs with diarrhea.8,9
- Fecal microbiome transplantation (FMT) is another treatment option that’s been investigated and shown to benefit dogs when compared to metronidazole.10
Taken together, a majority of cases are self-limiting and the evidence supports a shift in how we should be managing patients with acute diarrhea. Certainly, there are going to be exceptions and indications for the use of antibiotics but, in many cases, diarrhea will resolve without them. Dietary management (feeding a bland or highly digestible diet and adding fiber) and supplementing probiotics can lead to the same outcomes while, concurrently, benefiting the health of the gut microbiome. When there is no clear indication (e.g. suspicion of sepsis or a degenerative left shift on a CBC), antibiotics should not be the “go to” for treating acute cases of diarrhea. By reserving antibiotics for cases where they are truly indicated, veterinarians can help protect the gut microbiome, reduce the risk of antimicrobial resistance, and support both short- and long-term patient health.
Learn more on this topic and related topics:
References:
[1] Pharmaceutical Prescription in Canine Acute Diarrhoea: A Longitudinal Electronic Health Record Analysis of First Opinion Veterinary Practices Front. Vet. Sci. 2019. Vol 6:218. https://doi.org/10.3389/fvets.2019.00218
[2] U.S. Food and Drug Administration - Data on metronidazole
[3] Effects of metronidazole on the fecal microbiome and metabolome in healthy dogs. 2020; JVIM Vol 34 (5):pp 1853-1866. https://doi.org/10.1111/jvim.15871
[4] Characterization of microbial dysbiosis and metabolomic changes in dogs with acute diarrhea. PLOS One. May 2015. https://doi.org/10.1371/journal.pone.0127259
[5] A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy. November 2017. FEMS Microbiology Ecology Vol 93(11). https://doi.org/10.1093/femsec/fix136
[6] Metronidazole treatment of acute diarrhea in dogs: A randomized double blinded placebo-controlled clinical trial. 2020; JVIM Vol34(1):pp 98-104. https://doi.org/10.1111/jvim.15664
[7] Randomized controlled trial demonstrates nutritional management is superior to metronidazole for treatment of acute colitis in dogs. JAVMA 2022; Vol 260(S3): pp S23-S32. https://doi.org/10.2460/javma.22.08.0349
[8] A Randomized Double Blinded Placebo-Controlled Clinical Trial of a Probiotic or Metronidazole for Acute Canine Diarrhea. Front. Vet. Sci. 2019. Vol 6:163. doi: 10.3389/fvets.2019.00163
[9] Randomized, controlled trial evaluating the effect of multi-strain probiotic on the mucosal microbiota in canine idiopathic inflammatory bowel disease. Gut Microbes. 2017; Vol 8(5): pp 451-466. https://doi.org/10.1080/19490976.2017.1334754
[10] Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole. Front. Vet. Sci. 7:192. doi: 10.3389/fvets.2020.00192
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