The emergence and prevalence of MRSA, MRSP, and MRSS in pets and people

In the past 15 years, treatment of canine pyoderma and other infections in small animals has been made more difficult by the emergence of antibiotic resistance in staphylococcal bacteria in the form of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus pseudintermedius (MRSP) and methicillin-resistant Staphylococcus schleiferi (MRSS). MRSA infections have gained much public attention, and as veterinarians we need to understand methicillin-resistant infections and how they relate to our animal patients as well as to pet owners.

John Howard/Getty Images

Part 1 of this two-part article will give you the information you need to understand methicillin resistance in veterinary practice. Next month in part 2, you'll learn how to diagnose and treat methicillin-resistant skin infections as well as implement measures to reduce the spread of infection.

WHAT IS METHICILLIN RESISTANCE?

Methicillin is a beta-lactam antimicrobial introduced in the 1950s. It is relatively resistant to beta-lactamase, so it was used to treat penicillin-resistant staphylococci. However, bacterial resistance to methicillin emerged soon after its introduction.

Methicillin resistance is mediated by bacterial production of an altered penicillin-binding protein (PBP2a), which does not allow microbial binding of beta-lactam antibiotics. Therefore, methicillin-resistant isolates are resistant to all beta-lactam antibiotics (penicillins, cephalosporins, and carbapenems) and are also frequently resistant to other classes of antibiotics.1,2 The protein PBP2a is encoded by the mecA gene that resides on a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec).

A laboratory diagnosis of MRSP is actually done by testing for bacterial resistance against oxacillin, a similar antibiotic that is more stable for testing purposes.1,2 For S. aureus, cefoxitin has supplanted oxacillin as the marker for methicillin resistance.

MRSA: THE ORIGINAL MRS

MRSA in people

Staphylococcus aureus is often commensal in humans and is carried in (colonizes) the nasal passages of 29% to 38% of people.2,3 The prevalence of MRSA colonization in people in the United States is estimated to be 0.8% to 3.5%, but 30% to 40% of clinical S. aureus organisms isolated from human infections are methicillin resistant, and MRSA is now one of the most common nosocomial pathogens in the world.2,3

MRSA first emerged in the form of hospital-acquired infections within a year of the introduction of methicillin, but it was not until the mid-1980s that this problematic pathogen became a steadily increasing clinical problem. In 2003, a national hospital infection surveillance report revealed that 64.4% of healthcare-associated S. aureus infections in intensive care units were caused by MRSA, compared with 35.9% in 1992.4

Hospital-acquired MRSA is typically associated with resistance to multiple antibiotic classes in addition to beta-lactams, and it is reported to cause increased morbidity and mortality in people compared with methicillin-susceptible staphylococcal infections, usually associated with bacteremia, pneumonia, cellulitis, osteomyelitis, endocarditis, and septic shock.5 Identified risk factors for increased transmission of hospital-acquired MRSA include:

• Previous antimicrobial therapy (use of fluoroquinolones and cephalosporins has been linked to the emergence of resistance of methicillin-resistant staphylococci6,7)

• Immunosuppressive disease4

• Invasive medical instrumentation (e.g. intravenous and urethral catheters, bypass machines, prosthetic devices)4

• Surgery4

• Hospitalization4

In the mid- to late 1990s, methicillin-resistant staphylococcal infections that were genetically different from the hospital-acquired MRSA strains (and often susceptible to non-beta-lactam antimicrobials) were identified in healthy people without prior hospital exposure; since then community-associated MRSA has become an increasing problem.8 Although most community-associated MRSA infections have involved skin and soft tissue infections, serious invasive infections have also occurred, and the strains responsible for these infections have now entered the healthcare setting, obscuring the line between community and hospital strains.9 Identified risk factors that increase transmission of community-acquired MRSA include:

• Crowded living conditions4

• Shared bathing facilities4

• Intravenous drug use4

• Contact with someone else who is colonized or infected with community-acquired MRSA.4

So how prevalent is MRSA in people that work in veterinary-related settings? See the sidebar "By the numbers: MRSA colonization in veterinary professionals."

By the numbers: MRSA colonization in veterinary professionals

MRSA in pets

Methicillin-resistant staphylococci have been documented since the 1970s in large animals but was not reported in dogs until the 1990s.10 The prevalence of S. aureus colonization in dogs and cats is low and, when present, is usually assumed to have originated from an in-contact human.11-17 Epidemiological studies generally show that MRSA in pets belongs to the same strains as the dominant regional hospital-acquired and community-associated MRSA (in contrast to MRSA from livestock animals, which usually belongs to unique animal-associated lineages).18

Most small animals exposed to MRSA do not develop clinical disease; some become temporarily colonized, and most eliminate the organism. Colonization involves survival of MRSA on the body without any adverse effect. As in people, colonized animals usually show no adverse effects unless risk factors allow for development of clinical infection, including surgery, trauma, skin wounds, and immunosuppression. Optimal sites for MRSA screening in small animals have not been identified, but most references cite the use of nasal, rectal, and perineal swabs for bacterial culture.11,12,15,16,19

MRSA in dogs and cats is most frequently cultured from wounds, abscesses, otitis, and pyodermas.20 In one review of 40 dogs infected with MRSA compared with 80 dogs with methicillin-susceptible S. aureus (MSSA), risk factors identified were receipt of antimicrobial drugs (especially fluoroquinolones and beta-lactams, which increased risk of MRSA by five and three times, respectively) and intravenous catheterization.21 In a study comparing carriage of S. aureus in 50 dogs with normal vs. 59 dogs with inflamed skin, 16% of healthy dogs carried MSSA, and none carried MRSA. Staphylococcus aureus was cultured in 12% of dogs with inflamed skin, and 17% of these cases were methicillin resistant.20

Unlike MRSA in people, which is often associated with increased morbidity and mortality, there does not appear to be a significant difference in patient outcome between dogs infected with MSSA vs. MRSA, possibly because most infections are superficial (pyodermas and otitis) and not invasive. This is an important point to consider when counseling owners of pets with MRSA.21

Do pets contract MRSA from their owners?

Potential risk factors for acquisition of MRSA colonization by pets include contact with children and contact with human hospitals (especially if pets are allowed to lick patients or be fed treats by patients).22 Ownership of a pet by a person in the healthcare field was found to be a risk factor for MRSA colonization of the pets in one study,15 but not in another.2 Other studies have investigated the link between people and pets as well (see the sidebar "By the numbers: The MRSA link between people and pets").

By the numbers: The MRSA link between people and pets

Although pets that are colonized or infected with MRSA most likely contracted the bacteria from people (Figure 1), pets may have the capability to be carriers of MRSA and subsequently pass it back to in-contact people, though most of the evidence is circumstantial and cannot definitively prove the direction of transmission.12,16 In a study from the United Kingdom, MRSA carriage was 7.5% in 120 owners of MRSA-infected pets—much higher than the 1.5% carriage in the general U.K. population.23 In another report, 47 dogs and 52 cats were sampled in 66 households in which a MRSA-infected human patient resided; 11 of 99 pets (11%) representing nine (13.6%) households were MRSA-positive.24 In six of these households, the human and animal source strains were genetically concordant. For each day of delay in sampling the pet after the person's MRSA diagnosis, the chance of isolating MRSA from the pet decreased by 13.9%, suggesting that MRSA carriage in pets is temporary.24

1. Erythema multiforme complicated by MRSA in a dog. The owner was also affected by a nonhealing wound that was found to be infected with MRSA.

MRSP: A MORE COMMON CULPRIT IN PETS

While S. aureus is not considered to be a normal flora on dogs, companion animals do normally carry other species of Staphylococcus bacteria that can become pathogenic—S. pseudintermedius (previously known as Staphylococcus intermedius) most commonly and, less commonly, S. schleiferi (see below).16,19,20,25,26 In recent years, MRSP has emerged as a clinically important pathogen causing infections in dogs and cats.

Like MRSA, methicillin-resistance in S. pseudintermedius is mediated by PBP2a, which is encoded by the mecA gene. In addition to beta-lactam antibiotic resistance, most MRSP strains are also resistant to other classes of antibiotics.12,27

MRSP in people

Staphylococcus pseudintermedius is not considered to be a human pathogen, but it has occasionally been reported to cause severe infections in people,28 and people may be colonized by S. pseudintermedius, in some cases by the same strain of S. pseudintermedius that infects their pets.29-35 (See the sidebar "By the numbers: MRSP in people.")

By the numbers: MRSP in people

MRSP in pets

The prevalence of MRSP colonization varies depending on the population studied, with rates of 1.5% to 2% in dogs in the community and dogs admitted to veterinary hospitals16,20 and up to 7% of dogs with inflammatory skin disease (Figures 2A & 2B).20 The prevalence of MRSP in healthy cats was found to be 4%.36 As in MRSA in people, risk factors for the development of MRSP in animals include prior antibiotic use and hospitalization; emergence of methicillin-resistance in S. pseudintermedius may be due to selection pressure from antimicrobial use or horizontal spread of resistance factors from MRSA within the community.16,37-40

2A & 2B. An atopic Lhasa apso with erythematous and lichenified skin due to secondary spreading superficial pyoderma caused by MRSP.

Most clinical reports of methicillin-resistant infections have included superficial and deep pyoderma, otitis, and wound infections. Unlike MRSA in people, there is no indication that MRSP is more virulent than methicillin-susceptible S. pseudintermedius (MSSP), and most reported infections have been treated successfully, though possibly with a longer time to resolution.41

For example, treatment outcomes in dogs with methicillin-resistant pyoderma compared with outcomes in methicillin-susceptible cases were evaluated in a study of 123 MSSP and 93 MRSP clinical cases.42 The study found that most cases resolved (with topical treatment, systemic antimicrobial therapy, or both), regardless of methicillin sensitivity, although some MRSP cases took longer to resolve compared with the MSSP dogs. Corticosteroid administration was significantly associated with lack of resolution of all pyodermas at the first three- to four-week recheck examination.42

In a study comparing 56 dogs with MRSP infection with 112 control dogs with MSSP infections (most patients had pyoderma), mortality rate was not significantly different between study groups, and systemic administration of antimicrobials within 30 days before diagnosis of infection was significantly associated with risk of MRSP.40

Clinical cure of MRSP does not necessarily equate to microbiologic cure. In a sampling of dogs that initially had an MRSP pyoderma, 26 of 42 (61.9%) were still colonized with MRSP at follow-up, even though the pyoderma had clinically resolved. Additionally, in the same study of 60 dogs with pyoderma that did not have MRSP initially, MRSP was isolated from the skin after treatment in 17 dogs (28.3%).43

MRSS: A NEW PLAYER ON THE FIELD

Staphylococcus schleiferi subspecies coagulans is a relatively newly described coagulase-positive staphylococcal pathogen in dogs.13,20 Staphylococcus schleiferi subspecies schleiferi is a coagulase-negative variant that has been reported to be a normal component of human preaxillary flora and also has been implicated in human nosocomial infections, postsurgical infection, osteomyelitis, and endocarditis.44 This variant can also be pathogenic in animals and is increasingly found in methicillin-resistant infections.44

Although S. schleiferi is isolated less commonly in veterinary patients, one study found that S. schleiferi has a higher incidence of methicillin resistance then either S. aureus or S. pseudintermedius.45 In a study of 225 dogs with S. schleiferi infections (usually of the skin and ears), the most common underlying cause was atopy, and prior treatment with beta-lactam antibiotics was a risk factor for methicillin resistance. Of the 225 isolates (117 coagulase-negative and 95 coagulase-positive; 13 had no coagulase status reported), 129 (57%) were methicillin resistant, and coagulase-negative isolates were more likely to be methicillin resistant than coagulase-positive isolates.44

CONCLUSION

Now that you know more about how common methicillin-resistant staphylococci are in pets and the risks of infection to both people and pets in your veterinary practice, see next month's issue for a guide to diagnosing and treating these stubborn infections in your patients and steps you can take to curtail their occurrence.

Kimberly S. Coyner, DVM, DACVD

Dermatology Clinic for Animals of Las Vegas

5231 W. Charleston Blvd.

Las Vegas, NV 89146

REFERENCES

1. Deresinski S. Methicillin-resistant Staphylococcus aureus: an evolutionary, epidemiologic, and therapeutic odyssey. Clin Infect Dis 2005;40(4):562-573.

2. Kottler S, Middleton JR, Perry J, et al. Prevalence of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus carriage in three populations. J Vet Intern Med 2010;24(1):132–139.

3. Graham PL 3rd, Lin SX, Larson EL. A U.S. population-based survey of Staphylococcus aureus colonization. Ann Intern Med 2006;144(5):318–325.

4. Boucher HW, Corey GR. Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008;46(Suppl 5):S344-S349.

5. Cosgrove SE, Sakoulas G, Perencevich EN, et al. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 2003;36(1):53-59.

6. Dancer SJ. The effect of antibiotics on methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 2008;61(2):246-253.

7. Aldeyab MA, Monnet DL, Lopez-Lozano, JA, et al. Modelling the impact of antibiotic use and infection control practices on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus: a time-series analysis. J Antimicrob Chemother 2008;62:593-600.

8. Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care–associated methicillin-resistant Staphylococcus aureus infection. JAMA 2003;290(22):2976-2984.

9. Gordon RJ, Lowy FD. Pathogenesis of methicillin-resistant Staphylococcus aureus infection. Clin Infect Dis 2008;46(Suppl 5):S350-S359.

10. Tomlin J, Pead MJ, Lloyd DH, et al. Methicillin-resistant Staphylococcus aureus infections in 11 dogs. Vet Rec 1999;144(3):60-64.

11. Weese JS. Methicillin-resistant Staphylococcus aureus: an emerging pathogen in small animals. J Am Anim Hosp Assoc 2005;41(3):150-157.

12. Weese JS, van Duijkeren E. Methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius in veterinary medicine. Vet Microbiol 2010;140(3-4):418-429.

13. Morris DO, Rook KA, Shofer FS, et al. Screening of Staphylococcus aureus, Staphylococcus intermedius, and Staphylococcus schleiferi isolates obtained from small companion animals for antimicrobial resistance: a retrospective review of 749 isolates (2003-2004). Vet Dermatol 2006;17(5):332-337.

14. Lloyd DH. Reservoirs of antimicrobial resistance in pet animals. Clin Infect Dis 2007;45(Suppl 2):S148-S152.

15. Boost MV, O'Donoghue MM, James A. Prevalence of Staphylococcus aureus carriage among dogs and their owners. Epidemiol Infect 2008;136(7):953-964.

16. Hanselman BA, Kruth SA, Rousseau J, et al. Coagulase positive staphylococcal colonization of humans and their household pets. Can Vet J 2009;50(9):954-958.

17. Manian FA. Asymptomatic nasal carriage of mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) in a pet dog associated with MRSA infection in household contacts. Clin Infect Dis 2003;36(2):e26-e28.

18. McCarthy AJ, Lindsay JA, Loeffler A. Are all methicillin-resistant Staphylococcus aureus (MRSA) equal in all hosts? Epidemiological and genetic comparison between animal and human MRSA. Vet Dermatol 2012;23(4):267-275.

19. Fazakerley J, Nuttall T, Sales D, et al. Staphylococcal colonization of mucosal and lesional skin sites in atopic and healthy dogs. Vet Dermatol 2009;20(3):179-184.e

20. Griffeth GC, Morris DO, Abraham JL, et al. Screening for skin carriage of methicillin-resistant coagulase-positive staphylococci and Staphylococcus schleiferi in dogs with healthy and inflamed skin. Vet Dermatol 2008;19(3):142-149.

21. Faires MC, Traverse M, Tater KC, et al. Methicillin-resistant and –susceptible Staphylococcus aureus infections in dogs. Emerg Infect Dis 2010;16(1):69-75.

22. Lefebvre SL, Reid-Smith RJ, Waltner-Toews D, et al. Incidence of acquisition of methicillin-resistant Staphylococcus aureus, Clostridium difficile, and other health-care-associated pathogens by dogs that participate in animal-assisted interactions. J Am Vet Med Assoc 2009;234(11): 1404-1417.

23. Loeffler A, Pfeiffer DU, Lloyd DH, et al. Meticillin-resistant Staphylococcus aureus carriage in UK veterinary staff and owners of infected pets: new risk groups. J Hosp Infect 2010;74(3):282-288.

24. Morris DO, Lautenbach E, Zaoutis T, et al. Potential for pet animals to harbour methicillin-resistant Staphylococcus aureus when residing with human MRSA patients. Zoonoses Public Health 2012;59(4):286-293.

25. Fitzgerald JR. The Staphylococcus intermedius group of bacterial pathogens: species re-classification, pathogenesis and the emergence of meticillin resistance. Vet Dermatol 2009;20(5-6):490-495.

26. Vanni M, Tognetti R, Pretti C, et al. Antimicrobial susceptibility of Staphylococcus intermedius and Staphylococcus schleiferi isolated from dogs. Res Vet Sci 2009;87(2):192-195.

27. Bemis DA, Jones RD, Frank LA, et al. Evaluation of susceptibility test breakpoints used to predict mecA-mediated resistance in Staphylococcus pseudintermedius isolated from dogs. J Vet Diagn Invest 2009;21(1):53-58.

28. Van Hoovels L, Vankeerberghen A, Boel A, et al. First case of Staphylococcus pseudintermedius infection in a human. J Clin Microbiol 2006;44(12):4609-4612.

29. Morris DO, Boston RC, O'Shea K, et al. The prevalence of carriage of meticillin-resistant staphylococci by veterinary dermatology practice staff and their respective pets. Vet Dermatol 2010;21(4):400-407.

30. Paul NC, Moodley A, Ghibaudo G, et al. Carriage of methicillin-resistant Staphylococcus pseudintermedius in small animal veterinarians: Indirect evidence of zoonotic transmission. Zoonoses Public Health 2011;58(8):533-539.

31. Ishihara K, Shimokubo N, Sakagami A, et al. Occurrence and molecular characteristics of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius in an academic veterinary hospital. Appl Environ Microbiol 2010;76(15):5165-5174.

32. van Duijkeren E, Kamphuis M, van der Mije IC, et al. Transmission of methicillin-resistant Staphylococcus pseudintermedius between infected dogs and cats and contact pets, humans and the environment in households and veterinary clinics. Vet Microbiol 2011;150(3-4):338-343.

33. Sasaki T, Kikuchi K, Tanaka Y, et al. Methicillin-resistant Staphylococcus pseudintermedius in a veterinary teaching hospital. J Clin Microbiol 2007;45(4):1118-1125.

34. Tanner MA, Everett CL, Youvan DC. Molecular phylogenetic evidence for noninvasive zoonotic transmission of Staphylococcus intermedius from a canine pet to a human. J Clin Microbiol 2000;38(4):1628-1631.

35. Guardabassi L, Loeber ME, Jacobson A. Transmission of multiple antimicrobial-resistant Staphylococcus intermedius between dogs affected by deep pyoderma and their owners. Vet Microbiol 2004;98(1):23-27.

36. Abraham JL, Morris DO, Griffeth GC, et al. Surveillance of healthy cats and cats with inflammatory skin disease for colonization of the skin by methicillin-resistant coagulase-positive staphylococci and Staphylococcus schleiferi ssp. schleiferi. Vet Dermatol 2007;18(4):252-259.

37. Huerta B, Maldonado A, Ginel PJ, et al. Risk factors associated with the antimicrobial resistance of staphylococci in canine pyoderma. Vet Microbiol 2011;150(3-4):302-308.

38. Yoo JH, Yoon JW, Lee SY, et al. High prevalence of fluoroquinolone- and methicillin-resistant Staphylococcus pseudintermedius isolates from canine pyoderma and otitis externa in a veterinary teaching hospital. J Microbiol Biotechnol 2010;20(4):798-802.

39. Nienhoff U, Kadlec K, Chaberny IF, et al. Methicillin-resistant Staphylococcus pseudintermedius among dogs admitted to a small animal hospital. Vet Microbiol 2011;150(1-2):191-197.

40. Weese JS, Faires MC, Frank LA, et al. Factors associated with methicillin-resistant versus methicillin-susceptible Staphylococcus pseudintermedius infection in dogs. J Am Vet Med Assoc 2012;240(12):1450-1455.

41. Frank LA, Loeffler A. Meticillin-resistant Staphylococcus pseudintermedius: clinical challenge and treatment options. Vet Dermatol 2012; 23(4):283-291.

42. Bryan J, Frank LA, Rohrbach BW, et al. Treatment outcomes of dogs with methicillin-resistant and methicillin-susceptible Staphylococcus pseudintermedius pyoderma. Vet Dermatol 2012;23(4):361-368.

43. Beck KM, Waisglass SE, Dick HLN, wt al. Prevalence of meticillin-resistant Staphylococcus pseudintermedius (MRSP) from skin and carriage sites of dogs after treatment of their meticillin-resistant or meticillin-sensitive staphylococcal pyoderma. Vet Dermatol 2012;23(4):369-375.

44. Cain CL, Morris DO, Rankin SC. Clinical characterization of Staphylococcus schleiferi infections and identification of risk factors for acquisition of oxacillin-resistant strains in dogs: 225 cases (2003-2009). J Am Vet Med Assoc 2011;239(12):1566-1573.

45. Jones RD, Kania SA, Rohrbach BW, et al. Prevalence of oxacillin- and multidrug-resistant staphylococci in clinical samples from dogs: 1,772 samples (2001-2005). J Am Vet Med Assoc 2007;230(2):221-227.