Companion Animal Medicine

Antimicrobial Use and Antimicrobial Resistance in Companion Animal Medicine

Veterinarians, as well as other medical practitioners, have long relied on antimicrobial drugs in the treatment of infectious diseases. As antibiotic resistance becomes an issue of increasing concern, it is important for health professionals to be more selective in their use of these drugs. This module gives an overview of current antibiotic use in small animal practice, of factors leading to the development of antimicrobial drug resistance, and of clinical approaches to enhance the prudent use of antibiotics in veterinary practice.

Learning Outcomes

This submodule aims to describe the use of antimicrobial drugs in small animal practice, as well as how they may be used more judiciously. By the end of the module, you will be able to:

  1. identify the frequency of antimicrobial use in small animal practice.
  2. summarize the classes and types of antimicrobials commonly used in small animal practice.
  3. discuss the clinical applications where antimicrobial use may be reduced.
  4. describe the association between antimicrobial use and the occurrence of antimicrobial resistance.
  5. demonstrate understanding of the use of bacterial culture with antimicrobial susceptibility testing as an important diagnostic tool to support antimicrobial therapy.

 

Case Study Scenario

Veterinarian Dr. Colleen Murphy with Spaniel

Veterinarian Dr. Colleen Murphy with Spaniel

 

Two big dogs sleeping together on comfy chair

Two dogs sleeping together on comfy chair

Sue Harrington, DVM, is a small-animal clinician at the Kelva School of Veterinary Medicine. Don Bosch is a journalist with a local newspaper who has heard that antimicrobial use by veterinarians may contribute to the occurrence of antimicrobial resistance in humans, and this has led certain individuals and organizations to recommend a ban on antimicrobial use in animals. Don also has a dog that was recently treated with antimicrobials for a bladder infection and has an appreciation for the importance of these medications in treating his own pet. Don wants to interview Sue to write an article for his paper investigating antimicrobial use in small animals and the potential impact of antimicrobial use in small animals on the occurrence of antimicrobial resistance.

Antimicrobial Use in Small Animal Practice

Pill counter with batch of pills pouring into prescription bottle

Don: How often are antimicrobials prescribed in small animal practice?

Sue: Few studies describing antimicrobial use in small animal practice have been published. From the available evidence, antimicrobial use is common in small animal practice, although the overall quantity prescribed to small animals is often much smaller than in humans or food animal species (1). In one study population, antimicrobials accounted for 51 percent of prescriptions in small animals, and 52 percent of animals diagnosed with a new disease were prescribed an antimicrobial (2). In one veterinary teaching hospital, the rate of antimicrobial prescriptions ranged from 168 to 235 prescriptions per 1,000 admissions to the hospital (3).

Classes and Types of Antimicrobials Used in Small Animal Practice

Don: Which types of antimicrobials are used most frequently?

Sue: The most commonly prescribed antimicrobial class are ß-lactams (1-8) accounting for 67% of prescriptions in dogs and cats in a recent study (2). ß-lactam antimicrobials include penicillin, amoxicillin, ampicillin, and cephalexin, antimicrobials that are familiar to most people. Interestingly, many of the antimicrobials prescribed to small animals are identical to those prescribed for human infections.

Don: I had wondered about that. My dog was prescribed cephalexin for a bladder infection, as was my daughter for an ear infection.

Sue: That is not unexpected, since recently cephalexin was described as the most commonly prescribed antimicrobial in dogs, but it was rarely used in cats (2).

Table 1: The most frequently prescribed antimicrobials or antimicrobial classes to dogs and cats.

Dogs

Frequency of Prescriptions

 

 

Cats

Frequency of Prescriptions

Cephalexin

33%

 

 

Amoxicillin-clavulanic acid

40%

Amoxicillin-clavulanic acid

16%

 

 

Cefovecin

17%

Metronidazole

16%

 

 

Fluoroquinolones

12%

Fluoroquinolones

7%

 

 

Clindamycin

7%

Source: Murphy, 2010
*All other antimicrobials or antimicrobial classes were prescribed at frequency of 5 percent or less.

Table 2: The most frequently prescribed antimicrobials or antimicrobial classes to dogs and cats for diseases associated with the skin and urinary system.

  Skin−Dog Skin−Cat Urinary System−Dog Urinary System−Cat

Amoxicillin

4%

6%

25%

7%

Amoxicillin-clavulanic acid

14%

67%

38%

55%

Cefovecin

6%

22%

6%

10%

Cephalexin

67%

0

13%

0

Fluoroquinolones

4%

6%

19%

27%

 Source: Murphy, 2010
*All other antimicrobials or antimicrobial classes were prescribed at a frequency of less than 3 percent unless otherwise noted.

Table 3: The most frequently prescribed antimicrobials to dogs and cats for diseases associated with the gastrointestinal system.

Antimicrobial

Dogs

Cats

Amoxicillin-clavulanic acid

0

12%

Metronidazole

71%

50%

Tylosin

13%

 

 Source: Murphy, 2010
*All other antimicrobials or antimicrobial classes were prescribed at a frequency of less than 10 percent unless otherwise noted.

Table 4: The most frequently prescribed antimicrobials to dogs and cats for diseases associated with the respiratory system.

Antimicrobial

Dogs

Cats

Amoxicillin-clavulanic acid

18%

37%

Cefovecin

4%

11%

Chloramphenicol

14%

0

Doxycycline

11%

11%

Fluoroquinolones

15%

20%

Source: Murphy, 2010
*All other antimicrobials or antimicrobial classes were prescribed at a frequency of less than 10 percent unless otherwise noted.

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Now it's time to Check Your Understanding of Antimicrobial Drugs in Small Animal Medicine.

Antimicrobial Use and Antimicrobial Resistance in Companion Animal Medicine

Don: How does antimicrobial use affect antimicrobial resistance?

Sue: Antimicrobial use is an important contributor to the occurrence of antimicrobial resistance in both animals and humans. Several epidemiological studies in dogs have demonstrated that prior antimicrobial exposure was associated with antimicrobial resistance in a number of bacterial species, including E. coli isolates from feces (2,9,10), and opportunistic pathogens (11,12) like methicillin-resistant Staphylococcus aureus (13). An experimental study demonstrated that dogs treated with enrofloxacin were more effectively colonized with multidrug-resistant E. coli (14).

Recently, associations were observed between cephalexin use (a first-generation cephalosporin) in dogs and antimicrobial resistance to a ß-lactam inhibitor combination (amoxicillin-clavulanic acid), third-generation cephalosporins (ceftriaxone, cefoxitin) and cephamycins (ceftiofur). Dogs that were treated with cephalexin had a higher risk of resistance to these antimicrobials, three to eight times higher, when compared to dogs not treated with antimicrobials. The development of antimicrobial resistance was faster in dogs treated with cephalexin than in dogs not treated with antimicrobials. These are extremely important findings since cephalexin is the most commonly prescribed antimicrobial in dogs and these antimicrobials are critically important in the treatment of human infections. It suggests that the use of cephalexin may provide significant selection pressure for the occurrence of antimicrobial resistance.

Family washing bulldog in aluminum tub

 

 

 

 

 

 

 

 

 

 

 

 

Figure 1: A comparison of the times to loss of susceptibility (or the occurrence of antimicrobial resistance) in fecal E. coli isolates in dogs treated with cephalexin (red line) compared to dogs untreated with antimicrobials (black line).

Susceptibility to Ceftiofur

Chart: Susceptibility to Amoxicillin-clavulanic Acid

Chart: Susceptibility to Ceftriaxone

Legend: Cephalexin-Treated Dogs vs. Dogs Untreated with Antimicrobials

Interpretation
At any given time, the percentage of fecal E. coli isolates that were susceptible to the above antimicrobials was significantly lower in dogs treated with cephalexin (red line) than in dogs that were not treated with antimicrobials (black line). In other words, antimicrobial-resistant fecal E. coli isolates from dogs treated with cephalexin were isolated more frequently and at a faster rate than in dogs that were not treated with antimicrobials.

A comparison of the times to loss of susceptibility in fecal E. coli isolates in dogs treated with cephalexin compared to dogs untreated with antimicrobials. In all three step graphs, the cephalexin line remained the exact same while the untreated line differed from graph to graph. Cephalexin took a step drop to 0.85 at 7 days, 0.75 at 14 days, 0.70 at 28 days, and 0.60 at 90 days, remaining constant throughout till the end at day 180. In the Susceptibility to Ceftiofur graph, the untreated group remained at 1% of isolates susceptibility to TIO, until day 90 when it lowered to 0.80, where it remained till day 180. In the Susceptibility to Amoxicillin-clavulanic Acid graph, the untreated group immediately took a step down to 0.95% of isolates susceptible to AMC at day 7, 0.90 at day 14, and 0.80 at day 90 where it remained until day 180. In the Susceptibility to Ceftriaxone graph, the untreated group remained constant at 1% of isolated susceptibility to CRO throughout the entire 180 day period.

Note:

  1. Cephalexin treatment was started 0−12 hours after the Day 0 sample was collected and duration of cephalexin treatment ranged from 5 to 14 days.
  2. The study population were dogs (n=33 cephalexin treated, n=8 untreated) from primary care (nonreferral) small animal veterinary hospitals (n=21) in southern Ontario and were treated with cephalexin for a disease condition that was diagnosed and managed by the attending veterinarian.

Improving Antimicrobial Use

American Veterinary Medical Association official medical logo for veterinarian

Don: Since antimicrobial use is strongly associated with the occurrence of antimicrobial resistance that may pose a risk to human health, some individuals and groups argue that antimicrobial use in animals should be limited or discontinued.

Sue: Antimicrobial use in animals is extremely important to animal health and welfare. These are life-saving drugs and as veterinarians, we need to advocate for the welfare of animals. However, we also need to be cognizant of our role in public health. Antimicrobial use needs to be appropriate and prudent. Prudent use involves important factors such as when to use antimicrobials, length of therapy, and antimicrobial selection. Several veterinary professional organizations have published guidelines on the prudent use of antimicrobials (15−19).

Recently, a study looked at antimicrobial use by veterinarians and observed some areas where it could be improved. These include eliminating the common use of antimicrobials in elective, uncomplicated sterilization surgeries (e.g., spaying, castration) and reducing antimicrobial use in other clean surgical procedures. Antimicrobial use could likely be reduced for diseases such as feline lower urinary tract disease, feline upper respiratory tract disease, and canine infectious tracheobronchitis (2). In one population of cats, antimicrobial use could possibly be reduced by up to 25 percent if the common use of antimicrobials to treat feline upper respiratory tract disease and feline lower urinary tract disease was discontinued (2).

mortar and pestle with Rx symbol

Using antimicrobials only when appropriate is important, as are antimicrobial selection and application. There is some evidence to suggest that fluoroquinolones and cefovecin may be overused, particularly in cats (2) (Table 1)—and veterinarians need to ensure that the dosing of antimicrobials is appropriate. Dosing antimicrobials below the recommended dose could lead to treatment failure, thereby possibly requiring the use of additional antimicrobials. This may provide additional selection pressure for the occurrence of antimicrobial resistance. As well, dosing antimicrobials above the recommended dose ranges could lead to adverse events like toxicity.

Appropriate use of antimicrobials requires knowledge of many factors. Veterinarians synthesize this information with other clinical and diagnostic data to make the best choice for a positive clinical outcome.

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Now it's time to Check Your Understanding of Drugs for Uncomplicated Infections.

Table 5: The frequency of antimicrobial use in specific conditions diagnosed and managed by the attending veterinarian (3).

Condition

Frequency of diagnosis in outpatients
(if applicable)

Percentage of cases where antimicrobials are used

Percentage of overall nontopical (oral or parenteral) antimicrobial use in outpatients (if applicable)

Most frequently prescribed antimicrobials

Feline upper respiratory tract disease

 6% of all disease conditions diagnosed in cats

70%

13%

Amoxicillin-clavulanic acid, doxycycline and fluoroquinolones

Feline lower urinary tract disease

6% of all disease conditions diagnosed in cats

74%

13%

Amoxicillin-clavulanic acid and fluoroquinolones

Canine infectious tracheobronchitis

2% of all disease conditions in dogs

67%

4%

Amoxicillin, amoxicillin-clavulanic acid and chloramphenicol

Elective, uncomplicated sterilization surgeries

NA

24%

NA

Procaine penicillin, benzathine penicillin

Other clean surgical procedures

NA

60%

NA

Cephalosporins, ampicillin, procaine penicillin

Source: Murphy, 2010

Table 6: The dosing of antimicrobials by small animal veterinarians when compared to a readily available pocket-type formulary designed as a practical aid to veterinarians (20).

Species

Percentage dosed below referenced range

Percentage dosed above reference range

Overall percentage dosed outside of referenced range

Canine

18%

8%

26%

Feline

30%

19%

49%

 

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Now it's time to Check Your Understanding of the Study of Dogs Treated with Cephalexin.

Case Study Wrap-Up

Don: You commented that veterinarians synthesize clinical and diagnostic data to select antimicrobials for treatment. Could you expand on this further?

Sue: The initial decision is not which antimicrobial to use, but rather whether there is sufficient evidence to support the diagnosis of a bacterial infection. Veterinarians use a variety of information to make this decision, which typically includes a history gathered from the client, a physical examination of the pet, and knowledge of the diseases that are associated with the affected body site or sites. This includes knowledge of the frequency of diseases observed in their own practice and the underlying causes of disease, such as noninfectious causes like metabolic or degenerative diseases and toxicities, or infectious causes which can include bacterial, viral, or fungal agents.

Only diseases associated with bacterial agents may need antimicrobial therapy. In the previous examples, uncomplicated feline upper respiratory tract disease is frequently associated with viral agents, so antimicrobials may not be beneficial in treating this condition. As well, feline lower urinary tract disease is frequently not associated with any infection (i.e., sterile) and so consequently antimicrobial use usually would not be beneficial.

Some diseases, like canine kennel cough, may be associated with a bacterial infection but usually don’t need antimicrobial treatment, as they are often self-limiting. It is important to understand that antimicrobial use may be associated with adverse events like allergic reactions (like anaphylaxis), vomiting, diarrhea, and selection pressure for antimicrobial resistance. Further, you will be billing the client for medications that may not be necessary, some of which are expensive. Therefore, unnecessary use of antimicrobials may be associated with negative, unwarranted consequences.

Don: The information that veterinarians use to make decisions about antimicrobial use seems somewhat subjective. Are there any tests that veterinarians can use to help with the decision-making process?

Sue: Most clinical decisions are somewhat subjective. Obtaining objective data can improve the clinical decision process, and this can be as simple as taking a temperature or heart rate. For suspected or known bacterial infections, bacterial culture and antimicrobial susceptibility testing is a diagnostic test that can be used to support the diagnosis and guide treatment. This simply involves gathering the appropriate sample—like urine where a bladder or kidney infection is suspected—and sending this to an accredited diagnostic laboratory. There they grow the bacteria and then test the bacteria to see which antimicrobials are effective. The results are usually available in 48 hours for most infections. It is a very cost-effective test, especially when compared to other common diagnostics tests like serum biochemistry and thyroid panels.

Unfortunately, it is an underused diagnostic test. In one population of veterinarians, over a one-month period, data on over 1,000 antimicrobial prescriptions was collected and only 40 bacterial culture and antimicrobial susceptibility tests were performed to support the diagnosis for which these prescriptions were prescribed (2).

As with every diagnostic test, it has some limitations. Some veterinarians argue that they're going to treat with antimicrobials regardless, and therefore a culture and susceptibility would needlessly waste a client’s money. In some cases, immediate and appropriate antimicrobial treatment can save an animal’s life. But even in these situations, performing a culture and susceptibility is beneficial because veterinarians can use this information to choose the most appropriate antimicrobial once the results are available. In some cases, this could actually save a client’s money because veterinarians may learn that a cheaper antimicrobial may be effective or that the disease is not associated with a bacterial infection and therefore antimicrobial treatment could be discontinued. Unfortunately, it is difficult to obtain a sample from some parts of the body, such as the lung, and some organisms may be more difficult to culture as they require special conditions for growth, or grow very slowly. Despite these limitations, bacterial culture and antimicrobial susceptibility testing should be performed wherever possible and used as an additional tool to support diagnosis and treatment.

Don: Thanks, Sue. I appreciate the time you've taken today to discuss some of the issues about antimicrobial use in small animals, the role they play in animal health and the public health issue of antimicrobial resistance.

Sue: Thank you, Don. I appreciate you interest and hope that the information is useful to your readers. I look forward to your report.

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Now it's time to Check Your Understanding of Bacterial Culture and Antimicrobial Drug Susceptibility Testing.

Module Summary

  • A small number of antimicrobial drugs compose the most frequently prescribed antibiotics in veterinary medicine, and many of these are also prescribed in people.
  • Antimicrobial drug use can lead to resistance to the drug prescribed, and even other antibiotics.
  • Prudent, judicious use of antibiotics includes consideration of when to use them, length of therapy, and specific drug selection.
  • There are many situations in small animal practice in which antibiotic use is unnecessary and can be eliminated.
  • Bacterial culture and sensitivity are very useful guides for judicious antimicrobial drug use.

References

  1. DANMAP. 2007. Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark. Accessed May 2010.
  2. Murphy, CP. 2010. Antimicrobial resistance, antimicrobial use and infection control in community small animal veterinary hospitals in southern Ontario. (A thesis presented to the Faculty of Graduate Studies of the University of Guelph in partial fulfillment of requirements for the degree of Doctor of Philosophy.) University of Guelph, Guelph Ontario Canada. 
  3. Weese, JS. 2006. Investigation of antimicrobial use and the impact of antimicrobial use guidelines in a small animal veterinary teaching hospital: 1995−2004.  Journal of the American Veterinary Medical Association. 228:553−8.
  4. Watson, AD, and JE Maddison. 2001. Systemic antibacterial drug use in dogs in Australia. Australian Veterinary Journal. 79:740−6.
  5. Odensvik, K, K Grave, and C Greko. 2001. Antibacterial drugs prescribed for dogs and cats in Sweden and Norway 1990-1998. Acta Veterinaria Scandinavica. 42:189−98.
  6. Prescott, JF, WJ Hanna, R Reid-Smith, et al. 2002. Antimicrobial drug use and resistance in dogs. Canadian Veterinary Journal. 43:107−16.
  7. Rantala, M, K Holso, A Lillas, et al. 2004. Survey of condition-based prescribing of antimicrobial drugs for dogs at a veterinary teaching hospital. Veterinary Record. 155:259−62.
  8. Holso, K, M Rantala, A Lillas, et al. 2005. Prescribing antimicrobial agents for dogs and cats via university pharmacies in Finland—patterns and quality of information. Acta Veterinaria Scandinavica. 46:87−93.
  9. Murphy, CP, RJ Reid-Smith, JF Prescott, et al. 2009. Occurrence of antimicrobial resistance in selected bacteria in healthy dogs and cats presented to private veterinary clinics in Southern Ontario. Canadian Veterinary Journal. 50:1047−53.
  10. Ogeer-Gyles, J, KA Mathews, W Sears, et al. 2006. Development of antimicrobial drug resistance in rectal Escherichia coli isolates from dogs hospitalized in an intensive care unit. Journal of the American Veterinary Medical Association. 229:694−9.
  11. Medleau, L, RE Long, J Brown, et al. 1986. Frequency and antimicrobial susceptibility of Staphylococcus species isolated from canine pyodermas. American Journal of Veterinary Research. 47:229−31.
  12. Rantala, M, E Lahti, J Kuhalampil, et al. 2004. Antimicrobial resistance in Staphylococcus spp., Escherichia coli and Enterococcus spp. in dogs given antibiotics for chronic dermatological disorders, compared with non-treated control dogs. Acta Veterinaria Scandinavica. 45:37−45.
  13. Faires, MC. 2008. Evaluation of methicillin-resistant Staphylococcus aureus and characterization of S. pseudintermedius in dogs and cats. (A thesis presented to the Faculty of Graduate Studies of the University of Guelph in partial fulfillment of requirements for the degree of Master of Science) University of Guelph, Guelph Ontario Canada. 
  14. Trott, DJ, Filippich LJ, Bensink JC, et al. 2004. Canine model for investigating the impact of oral enrofloxacin on commensal coliforms and colonization with multidrug-resistant Escherichia coli. Journal of Medical Microbiology. 53: 439−43.
  15. Canadian Veterinary Medical Association. 2000. Guidelines on the prudent use of antimicrobial drugs in animals. Accessed May 2010.
  16. American Association of Feline Practitioners. 2001. Basic guidelines of judicious therapeutic use of antimicrobials in cats. Accessed May 2010. 
  17. American Veterinary Medical Association. 2006. American association of feline practitioners/American animal hospital association basic guidelines of judicious therapeutic use of antimicrobials. Accessed May 2010.
  18. American Association of Feline Practitioners/American Animal Hospital Association. 2006. Basic guidelines of judicious therapeutic use of antimicrobials. Accessed May 2010.
  19. Morley, PS, Apley MD, Besser TE, et al. 2005. Antimicrobial drug use in veterinary medicine. Journal of Veterinary Internal Medicine, 19:617−29.
  20. Allen, DG, JK Pringle, DA Smith, K Pasloske, and K Dayger. 2005. Handbook of Veterinary Drugs. Baltimore, Maryland. Lippincott Williams and Wilkins.