Introduction

Despite being inherently susceptible to virtually every known antimicrobial class, staphylococci are notorious antimicrobial resistant pathogens. The ability of staphylococci to become resistant was repeatedly demonstrated as the introduction of new drugs was typically followed (sometimes rapidly) by emergence of resistance. Included in this pattern was resistance to methicillin, which emerged not long after the use of methicillin began in 1959. While resistance to methicillin itself is not a major concern, methicillin-resistance is caused by production of an altered penicillin binding protein that has a poor affinity for beta-lactam antimicrobials and confers resistance not just to methicillin, but to virtually all beta-lactams (penicillins, cephalosporins, carbapenems). Methicillin-resistant staphylococci are also often resistant to a wide range of other antimicrobials, severely limiting treatment options. While was first noted as a problem in humans, methicillin-resistance has emerged as a pressing issue in companion animals, and there have been striking recent changes in the epidemiology of methicillin-resistant staphylococcal infection and colonization in dogs and cats.

There are two main groups of staphylococci; coagulase positive and coagulase negative. Coagulase positive species (e.g., S. aureus, S. pseudintermedius, S. schleiferi coagulans) are the most virulent and of greatest clinical relevance. Differentiation of these, or at a minimum, differentiation of S. aureus from other coagulase positive staphylococci is needed for both interpretation of zoonotic risks and the use of proper antimicrobial susceptibility testing methodology (since there are different standards for S. aureus versus other staphylococci). Coagulase negative staphylococci, apart from S. schleiferi schleiferi, tend to be of lesser or limited virulence and after often considered together as a single group, although there is some evidence of variation in virulence and clinical relevance. Knowing the type of Staphylococcus that is involved, therefore, is critical for proper management.

Methicillin-Resistant S. pseudintermedius (MRSP)

Staphylococcus pseudintermedius is the most clinically important Staphylococcus in dogs and a common commensal that can be found in or on a large percentage, if not all, healthy dogs, and a smaller percentage of cats. As with methicillin-susceptible S. pseudintermedius, MRSP can be found in or on healthy dogs and cats, and it appears that the rate of colonization is increasing in many regions. MRSP appears to have emerged and disseminated internationally in companion animals at a truly amazing rate, with rapid development of a very high level of drug resistance. MRSP infections are being identified virtually everywhere that people are looking, and the increase in incidence of disease, while not objectively reported, seems to be dramatic, particularly among dogs with pyoderma. Most infections are community-associated, particularly involving dogs with pyoderma and otitis, but hospital-associated transmission does occur and is of particularly concern among surgical patients.

MRSP is an opportunistic pathogen and colonization does not necessarily lead to disease. Indeed, it is likely that the vast majority of colonized animals never develop a clinical infection. Pre-operative MRSP carriage has been associated with increased risk of MRSP surgical site infection following TPLO.¹ The risk of infection in MRSP carriers in other situations has not been reported, but it is reasonable to assume that MRSP carriers are at some increased risk of MRSP infection when they are increased risk of any opportunistic infection. MRSP carriage is probably of limited concern to individual healthy dogs in the general population, but of greater relevance in dogs with comorbidities that increase the likelihood of any opportunistic infection (e.g., atopy) and those that undergo surgery. Additionally, MRSP carriers also presumably pose a risk to veterinary facilities as a source of hospital-associated transmission.

There is no indication that MRSP infections are inherently more serious than infections caused by methicillin-susceptible strains, however, they could ultimately be associated with increased morbidity and mortality because of failure of initial empirical antimicrobial therapy and limited treatment options.

Methicillin-Resistant S. aureus (MRSA)

MRSA tends to receive a higher profile than MRSP because of its huge impact in human medicine, however, it is a much less common cause of infection in dogs and cats than MRSP. Regardless, attention must be paid to this organism because of the potential for serious and difficult-to-treat infections, and the greater zoonotic implications.

As with MRSP, MRSA causes opportunistic infections and can be found in a small percentage of healthy dogs. It is assumed that the emergence of MRSA in companion animals is directly related to MRSA in humans, and humans are likely the source of most MRSA infections in dog and cats.

High MRSA carriage rates can also be found in specific dog populations such as households where another pet has an MRSA infection,² or during outbreaks in breeding or rescue kennels.^3,4 Being owned by a human healthcare worker and participation in hospital visitation programs have been identified as risk factors for MRSA colonization in dogs, and are logical based on the increased likelihood of exposure to colonized people.^5,6 Contact with children has also been identified as a risk factor.⁶ While these, and potentially other, risk factors should be considered, MRSA can be identified in any animal and absence of known risk factors should not lead to excluding MRSA from consideration.

Methicillin-Resistant S. schleiferi (MRSS)

Staphylococcus schleiferi consists of two subspecies, the coagulase positive S. schleiferi subsp. coagulans and coagulase negative S. schleiferi subsp. schleiferi. These are less common causes of infection compared with S. pseudintermedius and S. aureus, but a large percentage of diagnostic laboratories do not attempt to differentiate S. schleiferi coagulans from S. pseudintermedius or S. schleiferi schleiferi from other coagulase negative species, so there are limitations in understanding of the role of these species in disease. S. schleiferi coagulans is most commonly implicated in pyoderma and otitis externa in dogs, but other opportunistic infections such as urinary tract infection and pneumonia have been reported. Less in known about S. schleiferi schleiferi but has been increasingly implicated as a cause of pyoderma and otitis, and there is increasing concern that it may be more virulent than other coagulase negative staphylococci.

Therapy

Management of MRS infections follows the same principles of any other opportunistic infection. Indeed, there is no evidence that MRS infections are inherently more severe than susceptible staph infections; however, outcomes could be worse because of the failure of empirical antimicrobial therapy. It is reasonable to assume that MSSP and MRSP infections should have no different of an outcome if MRSP is quickly diagnosed and appropriately treated.

Systemic antimicrobial selection (when needed) should be based on in vitro susceptibility testing whenever possible because of the potential for highly drug resistant strains and the limited treatment options that may be available. MR-staph are resistant to all beta-lactams (penicillins, cephalosporins, carbapenems) and often many other drug classes. While there are often a variety of options for MRSA, choices may be few (and not optimal) for MRSP. Aminoglycosides and chloramphenicol are drugs to which MRSP is commonly (but not universally) susceptible, but there are potential issues with both of those.

Additional options may be available for cystitis, such as nitrofurantoin or fosfomycin. Drugs such as clindamycin, trimethoprim-sulfa, doxycycline and minocycline may be useful in some situations.

There is no evidence that infections caused by methicillin-resistant strains need longer or otherwise different treatment compared to infection caused by susceptible strains once appropriate antimicrobial therapy is started.

Local or topical treatment may be useful as an adjunctive or sole therapy. Topical antimicrobials or biocides are commonly used for superficial folliculitis and other focal, external infections. These facilitate delivery of high drug concentrations to the infection site, without systemic exposure, and can be highly effective.

References

1.  Nazarali A, et al. Association between methicillin-resistant Staphylococcus pseudintermedius carriage and the development of surgical site infections following tibial plateau leveling osteotomy in dogs. Journal of the American Veterinary Medical Association 2015;247:909–916.

2.  Faires MC, et al. An investigation of methicillin-resistant Staphylococcus aureus colonization in people and pets in the same household with an infected person or infected pet. J Am Vet Med Assoc 2009;235:540–543.

3.  Loeffler A, et al. Lack of transmission of methicillin-resistant Staphylococcus aureus (MRSA) between apparently healthy dogs in a rescue kennel. Vet Microbiol 2009.

4.  Floras A, et al. Sequence type 398 methicillin-resistant Staphylococcus aureus infection and colonisation in dogs. Vet Rec 2010;166:826–827.

5.  Boost M, et al. Characterisation of methicillin-resistant Staphylococcus aureus isolates from dogs and their owners. Clin Microbiol Infect 2007;13:731–733.

6.  Lefebvre SL, 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 interventions. J Am Vet Med Assoc 2009;234:1404–1417.

7.  Gorwitz RJ, et al. Strategies for clinical management of MRSA in the community: summary of an experts› meeting convened by the Centers for Disease Control and Prevention. 2006; http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html. Accessed Mar 1, 2006.

8.  Rich M, et al. Clindamycin-resistance in methicillin-resistant Staphylococcus aureus isolated from animals. Vet Microbiol 2005;111:237–240.

9.  Faires M, et al. Prevalence of inducible clindamycin resistant Staphylococcus aureus isolates from dogs and cats. ASM Conference on Antimicrobial Resistance in Zoonotic and Foodborne Pathogens 2008;60.