J. Scott Weese, DVM, DVSc, DACVIM
Staphylococci are common opportunistic pathogens and commensals that can be found on or in a large percentage of healthy animals and people. The clinical relevance of different staphylococci is variable, with some commonly associated with disease and others typically innocuous. In general, the coagulase positive staphylococci (predominantly S. aureus, S. pseudintermedius and S. schleiferi coagulans) are the most important staphylococci clinically in dogs and cats.
One frustrating trait of staphylococci is their ability to become resistant to antimicrobials. A key resistance marker is methicillin resistance. This is of concern because methicillin-resistant staphylococci are resistant to all beta-lactam antimicrobials (penicillins, cephalosporins, carbapenems) through the presence of the mecA gene, which confers production of an altered penicillin binding protein. Often, methicillin-resistant staphylococci are resistant to various other antimicrobial classes, thereby limiting treatment options.
Methicillin-Resistant Staphylococcus aureus
Methicillin-resistant S. aureus (MRSA) is a tremendous problem in human medicine and is among the most important infections in hospitalized individuals. Recently, MRSA has emerged as a significant community-associated pathogen, causing disease in people in the general population, including those that would previously be considered at low risk for infection. Skin and soft tissue infection predominate in people in the general population, however severe (including fatal) infections can occur. While MRSA has emerged in animals at a slower rate, this pathogen is now a significant concern in veterinary medicine.
The emergence of MRSA in household pets is a direct reflection of MRSA in humans, since humans are the ultimate source of MRSA in most pets. As MRSA has become more prevalent in people in the community, it was perhaps inevitable that exposure of domestic animals to MRSA would occur, particularly household pets, with which many people have close contact. The emergence of MRSA in pets has potentially significant implications on both animal and human health. There are significant public health concerns about MRSA in animals, most of which have only been preliminarily investigated. Most of the concern involves the potential for animals to act as reservoirs of MRSA with subsequent transmission to humans.
Initial reports of MRSA in household pets were case reports or case series of opportunistic infections, and shortly after MRSA was first recognized in pets, contact with the human healthcare system (hospital visitation animals, animals owned by healthcare workers or people that had been hospitalized) seemed to be over-represented. There have been subsequent reports of larger numbers of affected dogs, cats and rabbits internationally, and it is becoming apparent that while MRSA may have originated in humans, and that pet infections were linked more to specific human high-risk groups, there are separate veterinary issues that need to be addressed.
Among clinically infected animals, postoperative and wound infections and pyoderma are most commonly reported, with lesser numbers of intravenous catheter site infections, urinary tract infections and pneumonia. The incidence of MRSA infections in animals in unclear but seems to be increasing based on case reports and crude data from veterinary diagnostic laboratories. Organized surveillance is lacking.
As with humans, not all animals that encounter MRSA develop clinical disease. Presumably, only a small percentage become ill, while most eliminate the organism and an unknown percentage become colonized. Colonization involves survival of MRSA at one or more body sites, without any adverse effects. Although colonized animals are clinically normal, they may be at increased risk for subsequent development of MRSA infection (as has been reported in humans and horses). Colonized pets could also serve as a source of infection for other animals or humans.
Overall, the prevalence of MRSA colonization in the dog population appears to be low (0-3.5%), but is perhaps increasing. Less information is available regarding cats, but similar colonization rates have been reported. MRSA colonization has also been identified in a diverse range of species including rabbits, ferrets, turtles and birds. Risk factors for MRSA colonization have been minimally investigated in companion animals; antimicrobial therapy and contact with the human healthcare system (i.e., therapy dogs, dogs owned by healthcare workers) have been identified as risk factors. However, these represent a fairly superficial investigation of factors associated with MRSA infection or colonization and it is clear that further epidemiological studies are required to better elucidate the dynamics of MRSA infection and colonization in companion animals.
A recent development has been identification of the USA300 clone in household pets in North America. This is concerning because of the role USA300 in community-associated disease, particularly skin and soft tissue infection but also severe disease such as necrotizing pneumonia and necrotizing fasciitis. Similarly, there are recent reports of sequence type 398 (livestock-associated) MRSA infection or colonization of dogs in North America and Europe. Given the increasing prevalence and importance of this clone in some areas, close monitoring of the potential role of ST398 in infection of companion animals is required.
Recognition of MRSA in animals has raised a number of public health concerns. These involve direct transmission of MRSA from infected animals to humans and the potential for colonized animals to act as silent reservoirs of MRSA in the community. There are various reports of documented or suspected transmission of MRSA between people and household pets, both in households and in veterinary clinics. The strength of evidence has been variable, and concurrent identification of the same MRSA strain in both humans and animals does not necessarily mean that animals were the source of infection, but selected case studies as well as prevalence studies in animal contact groups certainly suggest that animals could act as a source of human infection. Veterinarians may be a high risk group for MRSA exposure. There have been conflicting results, but some studies have reported high rates of MRSA colonization in small animal veterinary personnel. Case reports have also demonstrated or suggested transmission of MRSA to personnel in veterinary clinics. Overall, it is likely that MRSA exposure is an occupational risk in small animal veterinary medicine and one that might be increasing.
There has been no objective evaluation of different treatment approaches for MRSA infections in small animals. Treatment decisions should be based on a variety of factors including infection severity, infection location and antimicrobial susceptibility of the MRSA strain. While MRSA receives much attention, it is important to remember that MRSA is still S. aureus, it is just more resistant to antimicrobials. Genera; principles of treatment and antimicrobial therapy still apply.
All MRSA isolates must be considered resistant to all beta-lactam antimicrobials, which limits the antimicrobial options, however there are virtually always one or more other acceptable options. Fluoroquinolone susceptibility may be present in vitro, however response to fluoroquinolones is unpredictable in humans, despite in vitro susceptibility, and resistance can develop quickly, even during treatment. For those reasons, fluoroquinolones are not considered appropriate for treatment of MRSA in humans, and there is no reason to think that the situation would be different in other species. There is also a phenomenon of inducible clindamycin resistance that can be problematic. Because the prevalence of inducible resistance can be 50% or higher in erythromycin-resistant strains, all isolates that are erythromycin-resistant (or where erythromycin-susceptibility is not reported) should be considered clindamycin resistant unless a D-test has indicated that inducible resistance is not present. Otherwise, antimicrobial choices should be made based on the antimicrobial susceptibility in conjunction with relevant factors such as infection site (ability of the drug to penetrate), infection character (presence of organic debris), patient age and patient health status (i.e., renal compromise). In humans, drugs such as vancomycin and linezolid are commonly used. In addition to being expensive, use of these drugs in animals is controversial because of their importance in human medicine and concerns about added pressure for further emergence of antimicrobial resistance. It is questionable whether these drugs should be used in veterinary medicine, and if they are used, it is critical that they only be used when absolutely necessary. In some regions, the use of drug classes such as these is not permitted.
Many MRSA infections may be amenable to local therapy (i.e., regional perfusion, intraarticular administration, use of antimicrobial impregnated materials), either as a sole or adjunctive treatment. Topical application of antiseptics or antimicrobials may represent a useful and necessary approach to treatment of external infections.
Despite the concerns regarding MRSA, it is a largely a treatable infection. One multicentre study reported a survival rate of 92% in dogs, with no difference between infections caused by MRSA and methicillin-susceptible S. aureus. The key is early diagnosis and commencement of appropriate therapy.
There is currently no indication that active decolonization is efficacious or indicated in colonized pets. Published and anecdotal reports indicate that MRSA colonization in cats and dogs is typically transient and that decolonization occurs naturally within a few weeks if recolonization is prevented. Therefore, there does not appear to be an indication for active, antimicrobial-based decolonization therapy in these animals. Further, it is difficult to envision how the nasal passages of a cat or dog could be properly and effectively treated with a topical antimicrobial agent. Household infection control measures should be implemented to reduce the risk of transmission while decolonization occurs.
It is unclear how (or if) the expansion of MRSA in pets can be controlled. As MRSA continues to be present in humans in the community, the risk of pet exposure will remain. Measures to both reduce the risk of exposure (i.e., good general hygiene, enhanced practices around people with MRSA infection or colonization) and the risk of development of MRSA infection are required. Prudent antimicrobial use is probably a critical factor. Objective evidence is currently minimal but a recent study identified prior fluoroquinolone use as a risk factor of MRSA versus methicillin-susceptible S. aureus infection.
Methicillin-Resistant S. pseudintermedius
While MRSA receives the most attention, methicillin-resistance can occur in other staphylococci, with variable implications for animal and human health. Staphylococcus intermedius has typically been considered to be the main cause of staphylococcal infections in dogs, however recent evidence indicates that most if not all isolates identified as S. intermedius in dogs and cats are actually the closely related species S. pseudintermedius. Accordingly, information previously published pertaining to S. intermedius can reasonably be assumed to actually involve S. pseudintermedius, and methicillin-resistant S. pseudintermedius (MRSP) is increasing greatly in the pet population in internationally.
A small percentage of healthy pets carry MRSP at any given time, in the nasal passages, gastrointestinal tract or on the skin. Population prevalence studies are currently limited but rates of 0-4.5% have been reported. Ongoing research suggests that higher rates may be present in some areas and it would not be surprising if the prevalence of MRSP colonization is truly increasing given the explosion of MRSP infections that are now being reported. The epidemiology of MRSP is an area that requires extensive study. Unlike MRSA, which appears to only transiently colonized dogs and cats, long-term carriage of MRSP is probably much more likely to occur because S. pseudintermedius is a normal commensal of dogs (and possibly cats). This may complicate control measures because of the potential for long-term or even lifelong reservoirs, with the potential for further transmission or recurrence of autogenous infections.
MRSP infections are an emerging concern and appear to becoming a much more common problem, particularly in cases of pyoderma, otitis and surgical site (especially TPLO) infection. Outbreaks of MRSP infections can occur in surgical facilities but the greatest concern is likely the large number of sporadic infections, which number well into the thousands in North America. In terms of animal health, MRSP is a much greater issue than MRSA, despite the attention that MRSA receives.
Underdiagnosis of MRSP has been a concern because it has been recently determined that previously used methods likely miss many MRSP infections. Changes to standard susceptibility testing guidelines for S. pseudintermedius were released in 2010, and will hopefully improve accuracy of diagnosis, provided laboratories use standard guidelines, something that is unfortunately not universal amongst veterinary diagnostic laboratories.
Like MRSA, all MRSP are resistant to all beta-lactams, and are frequently resistant to many other antimicrobials. Anecdotally, it appears that MRSP strains are usually more resistant than MRSA strains, and in many cases there are few reasonable treatment options. Therefore, this bacterium is of major concern for animal health. The high level of resistance complicates treatment of MRSP infections. There has been a dramatic and highly concerning increase in resistance patterns among MRSP over the past few years. Resistance is emerging to the small number of antimicrobials that were consistently effective in vitro, and in some cases there may be few to no viable treatment options. General principles of therapy are as described for MRSA, although inducible clindamycin resistance appears to be much less common than in MRSA. Local therapy may be particularly important because of the few systemic options that may be available.
Staphylococcus pseudintermedius is rarely implicated in disease in people, although infections have been reported and there may have been an increase in published case reports over the past year or two. One weakness of most reports of human infections has been the failure to isolate S. pseudintermedius from the presumed pet source of infection and demonstrate that the same strain was present in both the pet and human. Overall, the risk of zoonotic transmission of MRSP appears to be much less than for MRSA, but the risks are not negligible. Intra-household or intra-clinic transmission of MRSP between infected or colonized pets and their human contacts have been reported. While this has only been marginally investigated, it is apparent that transmission of S. pseudintermedius and MRSP is probably common in households with pets (however transient colonization, not infection, is the usual outcome). One study reported that in 44% of situations where S. pseudintermedius was isolated from a person, an indistinguishable strain could be found from their pet. This study also reported that people who said they did not regularly wash their hands after handling their pet were at increased risk of carrying S. pseudintermedius. These two factors strongly suggest that pets are often the origin of S. pseudintermedius in humans.
There is currently no objective information about MRSP control measures. Routine infection control practices are probably critical to reduce the risk of transmission from both infected and colonized patients. Despite the lower risk of zoonotic transmission, the highly drug resistant nature of many MRSP and the reports of zoonotic transmission mean that adequate attention should be paid to MRSP and it should not be completely overshadowed by concerns regarding MRSA.
Methicillin-Resistant S. schleiferi coagulans
Staphylococcus schleiferi coagulans (MRSS) is another coagulase positive species and methicillin-resistant strains have been reported, primarily in pyoderma and otitis in dogs. There seem to be regional differences in the prevalence of S. schleiferi, with it being rarely found in some regions and a relatively common cause of pyoderma in others. As with MRSP, MRSS can be highly drug resistant and difficult to treat. Management of MRSS is similar to that for MRSP, with an emphasis on local therapy whenever possible.
Currently, there is little concern about MRSS in humans. There have been no reports of transmission of MRSS from animals to humans. However, considering this bacterium is similar to MRSP and there are increasing concerns about zoonotic transmission of MRSP, it is prudent to consider that there could be a potential for zoonotic transmission, albeit probably low. General infection control practices should be used when managing MRSS, both in veterinary clinics and in the household.
Methicillin-Resistant Coagulase Negative Staphylococci
Coagulase negative staphylococci (CoNS) are a broad group that include S. sciuri, S. lentus, S. capitus, S. epidermidis, S. haemolyticus, S. felis, S. simulans, S. saprophyticus, S. schleiferi schleiferi, S. warneri and S. vitulinus, among others. They are often considered as a group and speciation is rarely performed, which may be a reasonable approach because there is currently little evidence that speciation affects treatment or prognosis. However, S. schleiferi schleiferi may be an important cause of pyoderma and otitis in some regions and S. felis may be an important cause of urinary tract infection in cats. Determination of the relative virulence of different CoNS is limited because few studies have adequately identified members of this group. CoNS are commonly found as commensal microflora of many body sites in a variety of species, and methicillin-resistant rates can be very high even in healthy animals in the community. Most CoNS are typically only pathogens of compromised hosts, and it is sometimes difficult to determine the relevance of isolation of MR-CoNS from a superficial site, as it could represent colonization or infection. Surgical site infections, wound infections, invasive device infections and bacteremia are most common. There is minimal concern about zoonotic transmission of MR-CoNS to immunocompetent people.
References are available upon request.