Practicing antimicrobial stewardship

Clinical AMS means thoughtful consideration of antimicrobial use and incorporation of decision-making questions

The WHO defines antimicrobials as Like many—if not all—veterinarians, I have any number of things in my day-to-day I know "should be" considered, communicated, and done. Antimicrobial stewardship (AMS), particularly as related to antimicrobial resistance (AMR), is near the top of that list due to its global prioritization by the World Health Organization (WHO) and other human and veterinary key groups.1

The WHO defines antimicrobials as "antibiotics, antivirals, antifungals, and antiparasitics, all medicines used to prevent and treat infections in humans, animals, and plants"1 and describes AMR as occurring "when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines," which "makes infections harder to treat and increases the risk of disease spread, severe illness, and death." 1

As most pet owner-veterinary interactions contain pharmaceutical pondering and potential prescribing, for me at least, a consequent "should be" better at AMS is warranted. For example, if your morning looks a bit like the below, then you may also encounter this, along with a few instances that, like myself, you may not have considered in an AMS-AMR context:

9:30 a.m.: Bella | Becky Smith - Straining to urinate dog

10 a.m.: Lily | Helen Jones - New puppy appointment

10:30 a.m.: Tux | Sheldon Mackenzie - Itchy cat

11 a.m.: Bo Jangles | Mia Smythe - Acute onset cough dog; Outbreak at doggie daycare?

What is antimicrobial stewardship?

The 2022 AAHA/AAFP Antimicrobial Stewardship Guidelines2 define AMS as "the actions veterinarians take to preserve the success and availability of antimicrobial drugs through careful oversight and responsible medical decision-making while protecting animal, public, and environmental health." Another definition is, AMS "aims to optimize antimicrobial therapy, maximizing clinical outcomes, while minimizing adverse effects on the patient (e.g. gastro-intestinal complications) and populations (e.g. selection pressure for resistance)."3 Antimicrobials are critical to practice. Day-to-day AMS, for me, means thoughtful consideration of antimicrobial use (AMU) through practical decision-making questions such as:

  • Are antimicrobials indicated in a given situation?
  • Which drug should I be using? At what dose? For what duration? By which route?
  • Should culture and susceptibility (C/S) be considered?
  • Are other actions indicated, along with (or instead of) antimicrobials (e.g. wound, or underlying disease management)?

Common clinical AMS examples

Case 1. 9:30 a.m.: Dog acutely straining to urinate. Bella is an eight-year-old female spayed (F/S) poodle cross and Becky worriedly says, "She's asking to go out more, but there are little bits of pee!" On exam, Bella is stable, shyly sweet, and a bit painful in her caudal abdomen. She has no prior history of lower urinary tract (LUT) signs.8

While there are other differentials (e.g. urolithiasis, neoplasia) to consider, I suspect we are all thinking that little Bella has a urinary tract infection, specifically bacterial cystitis.8

A urinalysis (ideally by cystocentesis) reveals a urine specific gravity of 1.038, pH 8, too numerous to count white blood cells and red blood cells, and bacteria (rods). Here is where clinical (and practical) AMS questions like the above creep into management.

Bella is an otherwise healthy middle-aged F/S dog with LUT signs and diagnostic support (urinalysis), that leads to our working diagnosis of sporadic (first time occurrence) bacterial cystitis. Should we advise a culture and susceptibility (C/S) on the collected cystocentesis urine?

In Bella's case, there isn't a clear correct answer. A C/S will identify 1) the likely bacterial suspect (which we can make an educated guess at as higher than 50 percent will typically be Escherichia coli and based on the rods on her urine cytology), 2) potential MDR, and 3) relevant AMS information (i.e. common bacteria at the practice, in addition to local bacterial C/S patterns). A management plan for Bella can move forward, with or without C/S, or a C/S can be considered at a later stage.

Therapy for Bella, as based on the antimicrobial urinary guidelines,8 may include analgesia (can allow delayed antimicrobial prescribing if we are wanting to wait for a C/S), and an antibiotic for the bacterial infection (a good choice is amoxicillin 11-22 mg/kg PO q12h duration three to five days).6,8 For Bella, and others like her, utilizing these resources makes AMS faster for clinicians.

Bella's prognosis is excellent, and we have provided Becky with a plan B if she doesn't respond as predicted: C/S, +/- laboratory diagnostics, imaging, and consideration of referral. This warrants an AMS "pat on the back," as your effort and time:

1) Aids drug selection, dose, frequency, and duration

2) Informs an AMS accountable therapy plan

3) Is supported by evidence- and expert-based guidelines

4) Likely reduces AMR risk to Becky and other "two legs" in Bella's universe

5) Allows for AMS for the clinic

6) Reduces potential longer-term costs to Becky, due to avoiding more intensive therapy related to inappropriate duration (compliance) and
resistance concerns.

Case 2. 10 a.m.: New puppy appointment. One Health is defined by the CDC as "a collaborative, multisectoral, and transdisciplinary approach … with the goal of achieving optimal health outcomes recognizing the interconnection between people, animals, plants, and their shared environment."9 This can feel (at least to me!) a bit overwhelming, but practical "day-to-day" One Health might simply look like Helen and her new puppy Lily (aged eight to12 weeks).

There are multiple things during the "puppy" preventive care appointment to discuss, (e.g. vaccination, nutrition, behavior, gastrointestinal (GI) parasites, fleas, and ticks) that reduce overall AMU as related to infection and build shared decision-making with pet owners.

For this example, we will focus on GI parasites and veterinary management (i.e. fecal and deworming). Lily's visit is 'One Health in action,' as endoparasite preventive care is tied to canine and zoonotic (human) health risks and the environment (pick up poop, decrease fecal parasite-pathogen shedding).

The expert- and evidence-based resources I lean on for GI parasites are the Companion Animal Parasite Council (CAPC),10 Canadian Parasitology Expert Panel (CPEP),11 AAHA/AAFP,2 and infectious disease in dogs in group setting recommendations.12 For a pup like Lily, these resources advise three to four fecal exams/year in the first year of life, and provide information on fecal tests and parasites, e.g. rounds (Toxocara, Toxascaris spp., Baylisascaris procyonis [important to differentiate from Toxocara]), hooks (Ancylostoma and Uncinaria spp.), tapes (Taenia spp, Diplydium caninum, Echinococcus spp.), Giardia, and whips (Trichuris vulpis).10-12

Lily's fecal test detects hookworms (Ancylostoma caninum), which is not surprising in a young pup. This is practical One Health, as this result is a concern for:

1) Lily, as without treatment a heavy GI burden can cause clinical disease or be fatal due to hookworm feeding

2) Helen, as hooks are zoonotic, e.g. human cutaneous larval migrans

3) The environment, fecal shedding, parasite burden

Hooks can be challenging, due to risk of reinfection (environmental) and "larval leak," whereby hooks that are dormant (arrested development) in a dog can be re-activated and re-establish infection.13

A further hookworm challenge has been the emergence of A. caninum MDR.14-16 It's thought that A. caninum MDR evolved from greyhound facilities due to antiparasitic use and selection pressure.15 Unfortunately, probably due to the movement of MDR hookworm infected dogs (rehoming, etc.), the spread of these worms presents a concern for the pet-dog population and is a larger One Health-AMS-MDR issue. Recent data indicates, while greyhounds have been the focus, MDR hooks have been detected in non-greyhound breeds, e.g. mixed breed, Yorkies, Labs, poodles, and dachshunds.17

Hookworm MDR should be suspected when fecal tests reveal that worms have not been killed by routine deworming and persistent infection is unrelated to larval leak or environmental re-infection. Fecal testing for resistance can be done by performing a pre- and post-treatment fecal egg count reduction test, molecular (PCR) testing, or in vitro drug bioassays.15 Emerging hookworm MDR is so important that a task force "to address multi-anthelmintic drug resistant A. caninum" has been formed by the American Association of Veterinary Parasitologists (AAVP).18

Fortunately for Lily, hookworm resistance is not detected, and her prognosis is excellent with therapy, preventive care, and communication to Helen. It is critical to convey to dog owners ongoing hookworm fecal tests and prevention is key, due to larval leak, resistance concerns, and environmental reinfection risks. Referencing guidelines for management can ease these conversations and provide resources for pet owners.10-12

Another "AMS cheer," this time for your preventive care effort to identify hookworms and potential MDR resistance, reduce both environmental contamination and zoonotic risk, and enable surveillance efforts for the veterinary and human medical communities to limit the geographic spread of MDR A. caninum. Additionally, there is a probable reduced cost to Helen as we have avoided Lily requiring more intensive therapy related her hookworm infestation.

Could your next appointments be AMS and One Health?

10:30 a.m.: Tix | Sheldon Mackenzie - Itchy cat

11 a.m.: Bo Jangles | Mia Smythe - Acute onset cough dog; Outbreak at doggie daycare?

11:30 a.m.: Sam | Rob Pauls - Chronic diarrhea (>3 weeks), six-year-old dog

I suspect there are many of you feeling like the "to-do" list is ever-expanding, and hopefully, these resources will allow for timely AMS in your day-to-day.

AMS RESOURCES FOR VETERINARIANS

Many infectious disease, AMU, and pet owner conversations can be assisted with these time-saving resources. Example communications and rationales: 1) avoid use of ciprofloxacin [unpredictable veterinary absorption, higher tier and impact on human use, MDR concern], or 2) choose amoxicillin (predictable absorption, lower tier and less impact on human use, lower MDR concern).6

Michelle Evason, BSc, DVM, DACVIM (SAIM), has worked in general practice, academia, specialty clinical practice, and in the animal health industry. She serves as global director of Veterinary Clinical Education for Antech and has published on numerous infectious diseases, antimicrobial stewardship, nutrition, and pet-owner education-related topics. Dr. Evason enjoys ferrying her children to various activities and fulfilling most "Canuck" stereotypes.

References

  1. World Health Organization (WHO), Accessed September 2022: https://www.who.int/en/news-room/fact-sheets/detail/antimicrobial-resistance
  2. Frey E, et al. 2022 AAFP/AAHA Antimicrobial Stewardship Guidelines, Accessed September 2022: https://www.aaha.org/aaha-guidelines/2022-aafpaaha-antimicrobial-stewardship-guidelines/home/
  3. Weese JS, et al. A multicenter study of antimicrobial prescriptions for cats diagnosed with bacterial urinary tract disease. JFMS. 2021 Oct;24(8):806-814. https://pubmed.ncbi.nlm.nih.gov/34709080/
  4. Antimicrobial Use Guidelines. International Society for Companion Animal Infectious Diseases (ISCAID). As accessed September 2022: https://iscaid.org
  5. Weese JSW, et al. American College of Veterinary Internal Medicine (ACVIM) Consensus Statement on Therapeutic Antimicrobial Use in Animals and Antimicrobial Resistance. JVIM 2015. J Vet Int Med.2015; 29:487–498. https://pubmed.ncbi.nlm.nih.gov/25783842
  6. Firstline-Clinical Decisions app: Antimicrobials for clinicians, downloaded from the Apple App store or Google Play Store, (select OVC-CPHAZ as your location). Accessed September 2022: https://www.wormsandgermsblog.com/2022/03/articles/animals/cats/antibiotic-prescribing-guidance-for-small-animal-veterinarians/
  7. British Small Animal Veterinary Association (BSAVA). Responsible use of antibacterials. PROTECT ME. Accessed September 2022: https://www.bsava.com/Resources/Veterinary-resources/Position-statements/Responsible-use-of-antibacterials
  8. Weese JSW, et al. International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Vet Jour. 2019. 247: 8-25. https://pubmed.ncbi.nlm.nih.gov/30971357/
  9. Centers for Disease Control (CDC). One Health. As accessed September 2022: https://www.cdc.gov/onehealth/index.html
  10. Companion Animal Parasite Council (CAPC) Intestinal Parasite Guidelines. Accessed September 2022: https://capcvet.org/guidelines/
  11. Canadian Parasitology Expert Panel (CPEP) Guidelines for the Management of Parasites in dogs and cats, 2019. Accessed September 2022: https://research-groups.usask.ca/cpep/index.php#Protocol
  12. Stull, et al. Infectious disease in dogs in group setting. 2016. Accessed September 2022: https://vet.osu.edu/sites/vet.osu.edu/files/documents/preventive-medicine/Infectious%20Disease%20in%20Dogs%20Final.pdf
  13. Weese JS, Evason ME. A Colour Handbook, Infectious Diseases of the Dog and Cat. CRC Press 2020.
  14. Castro J, et al. Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat? Parasit Vect. 2019;12, 576. https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3828-6
  15. Castro J, et al. Persistent or suspected-resistant hookworm infections. Clinician's Brief. 2020; August, 61-68. https://www.cliniciansbrief.com/article/persistent-or-suspected-resistant-hookworm-infections
  16. Castro J, et al. Multiple drug resistance in hookworms infecting greyhound dogs in the USA. Int. J. Parasitol. Drugs Drug Resist. 2021; 17:107-117. https://www.sciencedirect.com/science/article/pii/S2211320721000415
  17. Leutenegger CM, et al. High Frequency of the Benzimidazole Resistance Genetic Marker in the Pet Dog Population in Florida. ACVIM Proceedings 2022 Abstract ID06.
  18. American Association of Veterinary Parasitologists (AAVP) Hookworm Task Force. 2021, Accessed September 2022: https://www.aavp.org/aavp-forms-hookworm-task-force/

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