More than a buzzword: Antimicrobial stewardship to combat AMR (and how veterinarians can help!)

What is antimicrobial stewardship?

Antimicrobial stewardship: is it the next buzzword? It is not just the next buzz topic, but proper stewardship is a veterinarian’s responsibility.

Veterinarians need to be cognizant of their potential contributing role in developing antimicrobial resistance (AMR). As a profession, we must act in a One Health framework and consider our own patients and the animal population as a whole.

While we may see individual animals in small animal medicine, it is our duty to keep in mind the larger picture. This larger picture includes humans and environmental factors as well.

According to the American Veterinary Medical Association’s policies, “antimicrobial stewardship refers to the actions veterinarians take individually and as a profession [sig] to preserve the effectiveness and availability of antimicrobial drugs through conscientious oversight and responsible medical decision-making while safeguarding animal, public, and environmental health.”¹

Feel free to learn more by reviewing the AVMA’s policies page on the topic.

Dyar et al.² suggest that antimicrobial stewardship is a strategy to be viewed as a “coherent set of actions which promote using antimicrobials responsibly.” Simply put, use antimicrobials safely, appropriately, and conservatively.

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So, why should we, as veterinarians care?

One of public health’s biggest global concerns (pandemic aside) consists of the ever-increasing AMR rates.^3,4 I don’t know about you, but I cringe when I get resistant culture results back. I cringe because it means the patient will be that much harder to treat.

Furthermore, I must wonder how this happened. Has the patient had a ton of antibiotics thrown at him over time and developed resistance via natural selection, or has it occurred due to environmental exposures or other sources?

Annually, according to the Centers for Disease Control and Prevention (CDC), greater than 2.8 million people become infected with resistant fungi or bacteria, with over 35,000 deaths resulting.³

The degree of AMR in veterinary medicine is hard to estimate. Data collection on antimicrobial use in various species produces challenges. These occur due to variations in physiology between species. Additionally, management practices and disease pressures, and different ways to treat multiple conditions exist worldwide.^5(p16) Finally, the availability of medication options varies globally, and there isn’t always a one-size-fits-all protocol for therapy.

In a study by Wayne et al. in 2011⁶ on therapeutic antibiotic use patterns in dogs, they showed that 40% of the canine population studied had been prescribed antibiotics without infection evident. This clearly demonstrates that inappropriate antibiotic use has been present for a long time in veterinary medicine.

The act of consuming an antibiotic naturally selects for AMR, so by reducing consumption, we can help to reduce AMR.⁷

Veterinary medicine’s contribution to AMR

The use of antibiotics and other antimicrobials affects more than just the individual animal. Over time their use has led to natural selection for resistance and mutations within bacteria and other organisms to avoid the effects of the drugs. This leads to dangerous infections that are on the rise worldwide.

Problems in animal medicine in combating AMR include lack of evidence-based medicine and labeling claim concerns. It is critical to ensure proper education and training related to the use of antimicrobials, good record-keeping, and monitoring veterinary antibiotic use to ensure appropriate stewardship on the veterinary side.^5(p21)

Veterinarians prescribe antimicrobials, specifically antibiotics, almost as a reflex for various conditions. However, studies are starting to show that we are likely misusing them and overusing them in various conditions.^8–10

Many of our dosing regimens and durations of therapy have been extrapolated from human studies, but these extrapolations are outdated. Updated information is coming to light about the duration of antibiotic therapy for various conditions and conditions that no longer necessitate antibiotic therapy.

As we have seen with COVID-19, international borders mean nothing. AMR exists worldwide. This means that there is the risk that dangerous organisms could become issues not just in our veterinary patients but the human community as well. We need to ensure we are part of the solution, not part of the problem.

Read more from Dr. Tramuta-Drobnis: How the pandemic highlights veterinarians’ role in public health

In an ideal world, we would only prescribe antibiotics with a definitive diagnosis of infection either by cytology, culture, or histopathology with culture.

However, due to cost limitations, among other factors, this isn’t always possible. Because finance plays a role, clients limit our ability to practice the gold standard of medicine. However, that puts the onus on us to practice proper antibiotic stewardship!

How can small animal veterinarians practice proper stewardship? ^2,9,11–13

As an emergency clinician, I see all too commonly how misused antibiotics are, from inappropriate antibiotic selection to simply inappropriate prescribing of antimicrobials. Some vets still think that if an owner comes in for a problem, they expect a medication or a solution. However, there is nothing wrong with prescribing a bland diet or a pain medication and calling it a successful visit.

We can practice proper stewardship in several ways. By using the right antibiotic (selection) at the right time (disease appropriate) and at the right dose and duration, we can ensure judicious use and minimize negative impacts to individual animals and global populations long-term.

Suppose we reach for an antimicrobial to treat tick-borne diseases, respiratory, gastroenterological or urinary tract diseases, among others. In that case, we need to ensure we are treating the right disease with the effective, safe dose and the correct dosing interval for the right amount of time.

I will use antibiotics here, for example, but keep in mind that the concern for resistance occurs with not just antibiotics but antifungals, antiparasiticides, and other similarly related drugs. These recommendations are derived from the International Society for Companion Animal Infectious Diseases (ISCAID) treatment guidelines.

Antibiotic dose

Dose ranges have been established for individual drugs. These are based on scientific studies. However, some published doses have been known to be too high or too low as more data becomes available. Always ensure you are using an appropriate dose for the disease and species of concern.

Knowing where the drug is excreted may help you determine if you must go lower or higher on the dose range. Ensure that owners know that you are prescribing the dose based on the pet’s body weight and giving as directed and until finished.

Antibiotic duration

Many are questioning the duration of treatment for various ailments. For skin and urinary tract infections, for example, previous treatment duration wasn’t based on sound medical evidence, simply extrapolation. In addition, clinical experience and trial and error passed down from one generation to another account for many protocols.

However, now we are finding that not only is treating for 2-4 weeks not necessary for most disease states, but it may also increase the risk of resistance developing both in that patient individually and specifically in the organism targeted. ^14–16

Antibiotic selection

This is critical!

All too often, people reach for that big gun just because.

1. Make sure that you are reaching for the narrowest spectrum possible to still treat the disease of concern.
2. Make sure you review what organisms and diseases are best treated with what medication. Not all antibiotics are created equal. Not all drug classes reach the same types of organisms. Some drugs may purport to reach sufficient blood levels in vitro, but when applied in vivo, they fall short.
3. Consider all side effects, the patient’s age, the species, the clinical signs, and the client’s cost concerns if absolutely needed.

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Select conditions and antibiotic stewardship concerns^17,18

Let’s take a look at three clinical concerns and antibiotic use in these cases. Frequently, prescribed antibiotics for treating diarrhea, upper respiratory tract signs, and urinary tract signs are administered unnecessarily or incorrectly. Keep in mind it isn’t just when to reach for an antibiotic but reaching for the right one.

Antibiotics for acute diarrhea^11,17,18

We all know and use metronidazole. But make sure you are reaching for it only when necessary. What makes it necessary? Current studies to date have shown equivocal results when using metronidazole compared to a bland diet or a probiotic, suggesting that an antibiotic isn’t warranted in most cases of diarrhea.^19–21

Reach for it in patients where a probiotic and bland diet has failed, with severe hematochezia, with an ulcerative disease process (such as parvovirus), in cases of giardia not responding to fenbendazole and at select few other times.

But for the average run-of-the-mill diarrhea, recommendations suggest treating with a bland diet (ideally a prescription diet) with strict instructions to feed no people food, treats, or regular food until the stool is normal for a minimum of 24-48 hours. Then slowly reintroduce the regular food. Using a well-studied probiotic with a bland diet have been shown in studies and clinical experience to improve outcome.

Antibiotics for urinary tract infections^{9,11,17,18,22,23}

As an emergency veterinarian, you can imagine that I see a ton of feline interstitial cystitis (FIC) and, of course, urethral obstructions. I see many cats coming into me who have seen their primary care veterinarians in the weeks or months preceding their ER visit.

Often, these patients were prescribed an antibiotic or given a Convenia injection without a urine culture. These are otherwise healthy, eating, non-febrile cats who usually had stress identified in the 1-3 weeks preceding clinical signs. Though owners do not always recognize a stressor as such.

If you aren’t familiar with the studies and statistics on feline interstitial cystitis (FIC) (previously referred to as feline lower urinary tract syndrome), please review the more recent literature. Study percentages vary from < 0.5% to < 10 % of cats at any age showing lower urinary signs actually having an infection. With the average being < 1%. This includes healthy cats without underlying diabetes or kidney disease. (We all know these patients are more susceptible to UTIs and should be checked for it).

Cats with FIC need pain management (buprenorphine and or gabapentin), an antispasmodic such as prazosin (though some studies are equivocal with its use), and environmental modifications (critical). I never start an antibiotic in one of these patients. Finding white and red blood cells does not confirm infection.

A urine culture is warranted prior to starting antibiotics in cats because they just so infrequently get true infections. Usually, the cystitis is sterile and inflammatory mediated.

If owners do not want a culture, simply treat as discussed above and advise that the disease process can take 3-7 days to run its course. Inform male cat owners of risks of obstruction and signs to monitor for and stress that it is an emergency if seen.

The story is a bit different for dogs, and finding white blood cells and or bacteria in a sterile sample is more suggestive of infection. In female dogs, first-time UTI antibiotic treatment without culture isn’t wrong. The dose and duration of treatment recommended for these infections are under debate now, and where more studies are needed.

The adage that many of us were taught in vet school to treat all infections for two weeks or more – is going by the wayside. 3-5 days seems to be the standard for simple, uncomplicated, first-time urinary tract infections in female dogs. But more research is needed.^9(p11)

Of course, ideally, cultures should be performed in dogs before starting antibiotics. Cultures should be a must in females with subsequent infections or in any male dog. But don’t forget radiographs, for certain breeds at higher risk for urolith formation. We all know those Schnauzers and little white dogs seem to get stones just by looking at them funny.

Feel free to see the ISCAID guidelines for further information on urinary tract antibiotic use in dogs and cats.

Read more: Thinking sustainably in vet med: 3 tactics and 3 unexpected advantages

Antibiotics for respiratory tract illnesses^12,17,18

Feel free to see the ISCAID guidelines and a helpful review by Lappin et al. 2017 of respiratory antibiotic use in dogs and cats.

Cats

Knowing that upper respiratory tract infections (URIs) in cats are mostly viral in origin is paramount. Just because the owner expects antibiotics or some therapy doesn’t mean you give it to them. Additionally, ensure you choose the right antibiotic.

If you are concerned about secondary bacterial invaders, Clavamox may seem like a viable choice. But knowing that the most common bacterial organisms in the respiratory tract in cats are Chlamydia and Mycoplasma makes doxycycline the better option in vivo.¹²

Reach for an antibiotic in a cat with a URI only when your feline patient is anorexic, febrile, and has mucopurulent nasal discharge. Not utilizing antibiotics in cats with common URI signs in a still eating normothermic patient is paramount. This prevents inappropriate antibiotic use, saves doxycycline for when it is truly needed, prevents exposure to the patient’s microbiome and the potential risks leading to dysbiosis or AMR development.

Dogs²⁴

In dogs with URIs, most commonly seen as tracheobronchitis type disease, just because the dog is coughing doesn’t mean it warrants an antibiotic. Nine known organisms make up Canine Infectious Respiratory Disease Complex (CIRDC), previously referred to as Canine Infectious Tracheobronchitis.

In most adult dogs, therapy is supportive, and often medications aren’t needed. Education, however, is critical. By educating owners that, yes, they may cough, it will likely resolve on its own.

Only if that dog is coughing, not eating, febrile and lethargic then should you reach for an antibiotic, like doxycycline. Keep in mind the signalment of the patient. Puppies are more prone to develop pneumonia and may progress to severe illness rapidly. They may warrant intervention sooner. Consider exposure routes and age of the patient and any concurrent conditions that may predispose to worsening disease, warranting antibiotic therapy.

If you reach for an antibiotic, remember that the most common bacterial causes of URIs in dogs are Mycoplasma species and Bordetella bronchiseptica. Both of which are susceptible to doxycycline.

Ensure these patients remain hydrated, eat well, and utilize cough suppressants sparingly if there is no indication of pneumonia (as suppressing the cough increases pneumonia risk). If signs persist longer than 10 days or if significant systemic disease is demonstrated, reach for antimicrobials.

How small animal veterinarians can minimize negative effects on microbial selection processes

Always make sure that you are not treating the clients but your patients. If they do not elect to perform diagnostics, do not simply “try” an antibiotic and see if it works. Use supportive care such as appetite stimulants, cerenia, bland diet, subcutaneous fluids, and other modalities as warranted before reaching for antimicrobials.

However, if you reach for antibiotics, always ensure that you base antibiotic choices on drug class, use, and need, saving the big guns for severe disease and determined by culture.

Before reaching for antibiotics

1. Make sure you consider signalment, history, and physical exam findings.
2. Determine the most likely etiology. If antimicrobials are warranted, select the most narrow-spectrum option feasible.
3. Properly investigate differentials, including non-infectious causes, ideally before prescribing antimicrobials. Perform appropriate diagnostics first. In the ACVIM Consensus Statement from 2015, they clearly discuss that early diagnostics rather than empiric antimicrobial use need be a priority in the fight against AMR.¹⁴
4. If using an antimicrobial and the patient isn’t responding, perform additional diagnostics before simply switching from one drug to a different class. Investigate before simply prescribing a new medication or combining drugs. Make sure you do not fail to consider alternative etiologies.¹⁴
5. Sadly, cost plays a role in drug selection. While this is a reality, it needs to be the final consideration if a client’s concern. Select the drug of choice based on the preceding 4 factors, only letting cost guide you when necessary.
6. Do your due diligence! Know and understand the disease process of concern. Know what the scientific literature recommendations are currently.

One final key point to make is that we need to educate clients in addition to all we are doing. We need to inform them

• If we don’t use an antibiotic and they were expecting one, why we are not reaching for one.
• If we use an antibiotic, it is our duty to discuss any side effects such as vomiting, diarrhea, or a decreased appetite. Additionally, we need to discuss risks such as cartilage damage in young animals on fluoroquinolones.
• We need to ensure owners understand that the dosing frequency is critical to how it works. It is paramount to give the fully prescribed course. We do not want to undertreat an infection. Furthermore, we can actually increase the selection for resistance by improperly treating with incorrect dosages, frequencies, and durations.¹³

Before reaching for antibiotics without pause, take a look at the AVMA’s great veterinary checklist²⁵ on Antimicrobial Stewardship. Use this as a guideline for your individual clinic and review your prescribing practices to make sure you exercise appropriate antimicrobial stewardship for your patients, your practice, and public health.

Antimicrobial stewardship and some parting thoughts

Antibiotic stewardship ensures the preservation of a therapeutic arsenal. With powerful medical advances have come great responsibility. We must ensure that we protect human and animal health, our food supply and ensure that the medications remain effective. To do so warrants prudent, sensible, sound use of the various products available to us. It also requires us to be knowledgeable of the scientific evidence newly evaluated.

It is no longer acceptable to simply do something because that is how you were taught. We as a profession and you as an individual need to strive for growth. This includes developing new practices that follow the trends of the day, such as no longer treating with two weeks or longer of antibiotics for most conditions, and include developing protocols based on the evidence available.

There are definitely times and places for antimicrobial use. Still, the era of simply giving everything antibiotics, not performing diagnostics, and treating owners rather than the patient in front of you is long gone. We need to be part of the solution and not part of the AMR problem.

In combination with our counterparts in human medicine, it is our job to safeguard the effective and safe use of antimicrobials in both the veterinary and human fields, minimizing the risks globally while treating our patients using up-to-date, evidence-based medicine recommendations.

Erica Tramuta-Drobnis, VMD, MPH, CPH is the Founder & CEO ELTD of One Health Consulting, LLC, as well as a freelance writer, consultant, researcher, public health professional and small animal veterinarian.

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References

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